Dissertations / Theses: 'Gut-brain axis'

1

Altera, Annalisa. "Gut-brain axis: the role of microbiota in gut and brain ageing." Doctoral thesis, Università di Siena, 2022. http://hdl.handle.net/11365/1209555.

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In the last decade there has been a growing interest in the reciprocal impact occurring between the gut and the brain and this is well conceptualized in the gut-brain axis notion. The gut-brain axis is the bidirectional communication route between the “little brain” (gut) and the “big brain” (brain). There are several factors that play an important role in this axis but it has become more and more evident that the gut bacteria represent a key component. This has led to the new concept of the microbiota-gut-brain axis, emphasizing the importance of the gut microbiota in this axis. The gut has evolved with bacteria in a symbiotic way and the human gut hosts about 1014 bacterial cells. Researches in the last years have highlighted the importance of the microbiota not only for gut functions but also for the central nervous system (CNS) development, physiology and pathology. However, there are different factors that influence the composition of the gut microbiota (mode of delivery, diet, stress and ageing). In particular, the composition of the gut microbiota changes with ageing: in the adults the majority of taxa are Bacteroidetes and Firmicutes while the elderly has a different composition of the gut microbiota. Some studies have reported a decrease in Bifidobacteria and an increase in Escherichia, Enterobacteriaceae and Clostridium difficile in the elderly. Interestingly, the centenarians apparently have no changes in gut microbiota in comparison to adult, further highlighting the importance of gut bacteria in longevity. Ageing is a physiological process related to the loss of function in different body systems and also associated with a decline in cognitive functions. It has become more and more evident that events taking place in the gut play a major role in the ageing process and in age-related diseases. Faecal microbial transplant (FMT) is a technique that consists in the transfer of gut microbiota from a donor to a recipient (usually via an oral gavage in rodents or colonoscopy in humans) and allows to establish a donor-like microbiota in the gastro-intestinal tract of the recipient. FMT is used to treat recurrent Clostridium difficile infections but there are studies trying to test this technique in the treatment of other pathologies such as irritable bowel syndrome, inflammatory bowel disease and constipation. It is also worth noticing that the imbalance in the composition of the gut microbiota (dysbiosis) has been associated with a plethora of neurological disorders. In this context FMT is being investigated as a therapeutic option not only for treatment of gut disorders but also for diseases of the CNS. The present thesis illustrates a series of experiments by which we tested the impact of FMT from aged donor mice into young adult recipients. Controls were carried out operating FMT from young adult donor mice to age-matched recipients. Following transplantation, characterization of the microbiota and metabolomics profiles along with a series of cognitive and behavioural tests were carried out. Label-free quantitative proteomics was employed to evaluate protein expression in the hippocampus and gut after the transplant. In addition, in the attempt to elucidate the mechanisms underlying microbiota-host interactions within the framework of the gut-brain axis, we worked on setting up a procedure to tracking down and visualize bacterial metabolites (such as peptides and lipids) that are thought to play a role acting as signaling molecules. To this end, we used copper-catalysed azide-alkyne cycloaddition (CuAAC) click chemistry, a biorthogonal reaction of widespread utility throughout medical chemistry and chemical biology. We sought to optimize click-based protocols to detect the production of lipids in gut-bacteria to track the metabolism of active bacterial cells. This technique use click chemistry to stain synthetic (e.g., noncanonical) precursors incorporated into bacterial cell biomass. After incorporation, the artificial molecules can be fluorescently detected via azide-alkyne reaction and visualized by confocal microscopy. FMT from aged mice into adult recipients affected spatial learning and memory while we did not observe effects on locomotion and explorative behaviour. Alongside, there was an alteration in the expression of proteins related to synaptic plasticity and neurotransmission in the hippocampus which was not observed in controls. FMT from aged into young adult mice did not induce a significant increase in glial fibrillary acidic protein expression in hippocampal astrocytes suggesting the lack of an overt neuroinflammatory response. On the other hand, a significant increase in the expression of F4/80, a typical trait of the ageing brain, was observed in microglial cells resident in the fimbria. Gut permeability and levels of systemic and local (hippocampus, gut) cytokines were not affected. As regards click chemistry, we used Bacteroides thetaiotaomicron grown in minimal medium supplemented with palmitic acid alkyne (PAA) and stained this molecule using an azide-containing fluorescent dye. After palmitic acid staining, co-culture experiments were performed to assess the transfer of this bacterial product to eukaryotic cell lines (CaCo2 and SK-N-SH cell lines). The successful transfer to host cells was confirmed by confocal microscopy. Results obtained in FMT experiments highlighted the importance of the gut microbiota on protein expression and functions of CNS. These results support the key role of microbiota in gut-brain axis and it would be of great importance to get more insight into the restoration of a young microbiota in the elderly to try to improve cognitive functions and the quality of life. Click chemistry experiments demonstrate that this technique could be employed to track molecules produced by gut bacteria to unveil their role in host-microbe interactions.

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2

Raybould, H. E. "Actions of cholecystokinin on the brain-gut axis." Thesis, University of Liverpool, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.380098.

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3

Strati, Francesco. "The microbiota-gut-brain axis: characterization of the gut microbiota in neurological disorders." Doctoral thesis, Università degli studi di Trento, 2017. https://hdl.handle.net/11572/368893.

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The human gut microbiota plays a crucial role in the functioning of the gastrointestinal tract and its alteration can lead to gastrointestinal abnormalities and inflammation. Additionally, the gut microbiota modulates central nervous system (CNS) activities affecting several aspect of host physiology. Motivated by the increasing evidences of the role of the gut microbiota in the complex set of interactions connecting the gut and the CNS, known as gut-brain axis, in this Ph.D. thesis we asked whether the gastrointestinal abnormalities and inflammation commonly associated with neurological disorders such as Rett syndrome (RTT) and Autism could be related to alterations of the bacterial and fungal intestinal microbiota. First, since only few reports have explored the fungal component of the gut microbiota in health and disease, we characterized the gut mycobiota in a cohort of healthy individuals, in order to reduce the gap of knowledge concerning factors influencing the intestinal microbial communities. Next, we compared the gut microbiota of three cohorts of healthy, RTT and autistic subjects to investigate if these neurological disorders harbour alterations of the gut microbiota. Culture-based and metataxonomics analysis of the faecal fungal populations of healthy volunteers revealed that the gut mycobiota differs in function of individualsâ€™ life stage in a gender-related fashion. Different fungal species were isolated showing phenotypic adaptation to the intestinal environment. High frequency of azoles resistance was also found, with potential clinical significance. It was further observed that autistic subjects are characterized by a reduced incidence of Bacteroidetes and that Collinsella, Corynebacterium, Dorea and Lactobacillus were the taxa predominating in the gut microbiota of autistic subjects. Constipation has been associated with different bacterial patterns in autistic and neurotypical subjects, with constipated autistic individuals characterized by higher levels of Escherichia/Shigella and Clostridium cluster XVIII than constipated neurotypical subjects. RTT is a neurological disorder caused by loss-of-function mutations of MeCP2 and it is commonly associated with gastrointestinal dysfunctions and constipation. We showed that RTT subjects harbour bacterial and fungal microbiota altered from those of healthy controls, with a reduced microbial richness and dominated by Bifidobacterium, different Clostridia and Candida. The alterations of the gut microbiota observed did not depend on the constipation status of RTT subjects while this microbiota produced altered SCFAs profiles potentially contributing to the constipation itself. Phenotypical and immunological characterizations of faecal fungal isolates from RTT subjects showed Candida parapsilosis as the most abundant species isolated in RTT, genetically unrelated to healthy controlsâ€™ isolates and with elevated resistance to azoles. Furthermore these isolates induced high levels of IL-10 suggesting increased tolerance and persistence within the host. Finally, the importance of multiple sequence alignment (MSA) accuracy in microbiome research was investigated comparing three implementations of the widely used NAST algorithm. By now, different implementations of NAST have been developed but no one tested the performances and the accuracy of the MSAs generated with these implementations. We showed that micca, a new bioinformatics pipeline for metataxonomics data improves the quality of NAST alignments by using a fast and memory efficient reimplementation of the NAST algorithm.

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4

Strati, Francesco. "The microbiota-gut-brain axis: characterization of the gut microbiota in neurological disorders." Doctoral thesis, Università degli studi di Trento, 2017. http://hdl.handle.net/10449/38243.

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The human gut microbiota plays a crucial role in the functioning of the gastrointestinal tract and its alteration can lead to gastrointestinal abnormalities and inflammation. Additionally, the gut microbiota modulates central nervous system (CNS) activities affecting several aspect of host physiology. Motivated by the increasing evidences of the role of the gut microbiota in the complex set of interactions connecting the gut and the CNS, known as gut-brain axis, in this Ph.D. thesis we asked whether the gastrointestinal abnormalities and inflammation commonly associated with neurological disorders such as Rett syndrome (RTT) and Autism could be related to alterations of the bacterial and fungal intestinal microbiota. First, since only few reports have explored the fungal component of the gut microbiota in health and disease, we characterized the gut mycobiota in a cohort of healthy individuals, in order to reduce the gap of knowledge concerning factors influencing the intestinal microbial communities. Next, we compared the gut microbiota of three cohorts of healthy, RTT and autistic subjects to investigate if these neurological disorders harbour alterations of the gut microbiota. Culture-based and metataxonomics analysis of the faecal fungal populations of healthy volunteers revealed that the gut mycobiota differs in function of individuals’ life stage in a gender-related fashion. Different fungal species were isolated showing phenotypic adaptation to the intestinal environment. High frequency of azoles resistance was also found, with potential clinical significance. It was further observed that autistic subjects are characterized by a reduced incidence of Bacteroidetes and that Collinsella, Corynebacterium, Dorea and Lactobacillus were the taxa predominating in the gut microbiota of autistic subjects. Constipation has been associated with different bacterial patterns in autistic and neurotypical subjects, with constipated autistic individuals characterized by higher levels of Escherichia/Shigella and Clostridium cluster XVIII than constipated neurotypical subjects. RTT is a neurological disorder caused by loss-of-function mutations of MeCP2 and it is commonly associated with gastrointestinal dysfunctions and constipation. We showed that RTT subjects harbour bacterial and fungal microbiota altered from those of healthy controls, with a reduced microbial richness and dominated by Bifidobacterium, different Clostridia and Candida. The alterations of the gut microbiota observed did not depend on the constipation status of RTT subjects while this microbiota produced altered SCFAs profiles potentially contributing to the constipation itself. Phenotypical and immunological characterizations of faecal fungal isolates from RTT subjects showed Candida parapsilosis as the most abundant species isolated in RTT, genetically unrelated to healthy controls’ isolates and with elevated resistance to azoles. Furthermore these isolates induced high levels of IL-10 suggesting increased tolerance and persistence within the host. Finally, the importance of multiple sequence alignment (MSA) accuracy in microbiome research was investigated comparing three implementations of the widely used NAST algorithm. By now, different implementations of NAST have been developed but no one tested the performances and the accuracy of the MSAs generated with these implementations. We showed that micca, a new bioinformatics pipeline for metataxonomics data improves the quality of NAST alignments by using a fast and memory efficient reimplementation of the NAST algorithm.

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5

Strati, Francesco. "The microbiota-gut-brain axis: characterization of the gut microbiota in neurological disorders." Doctoral thesis, University of Trento, 2017. http://eprints-phd.biblio.unitn.it/1917/1/STRATI_PhD_thesis_R1_2017.01.13.pdf.

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The human gut microbiota plays a crucial role in the functioning of the gastrointestinal tract and its alteration can lead to gastrointestinal abnormalities and inflammation. Additionally, the gut microbiota modulates central nervous system (CNS) activities affecting several aspect of host physiology. Motivated by the increasing evidences of the role of the gut microbiota in the complex set of interactions connecting the gut and the CNS, known as gut-brain axis, in this Ph.D. thesis we asked whether the gastrointestinal abnormalities and inflammation commonly associated with neurological disorders such as Rett syndrome (RTT) and Autism could be related to alterations of the bacterial and fungal intestinal microbiota. First, since only few reports have explored the fungal component of the gut microbiota in health and disease, we characterized the gut mycobiota in a cohort of healthy individuals, in order to reduce the gap of knowledge concerning factors influencing the intestinal microbial communities. Next, we compared the gut microbiota of three cohorts of healthy, RTT and autistic subjects to investigate if these neurological disorders harbour alterations of the gut microbiota. Culture-based and metataxonomics analysis of the faecal fungal populations of healthy volunteers revealed that the gut mycobiota differs in function of individuals’ life stage in a gender-related fashion. Different fungal species were isolated showing phenotypic adaptation to the intestinal environment. High frequency of azoles resistance was also found, with potential clinical significance. It was further observed that autistic subjects are characterized by a reduced incidence of Bacteroidetes and that Collinsella, Corynebacterium, Dorea and Lactobacillus were the taxa predominating in the gut microbiota of autistic subjects. Constipation has been associated with different bacterial patterns in autistic and neurotypical subjects, with constipated autistic individuals characterized by higher levels of Escherichia/Shigella and Clostridium cluster XVIII than constipated neurotypical subjects. RTT is a neurological disorder caused by loss-of-function mutations of MeCP2 and it is commonly associated with gastrointestinal dysfunctions and constipation. We showed that RTT subjects harbour bacterial and fungal microbiota altered from those of healthy controls, with a reduced microbial richness and dominated by Bifidobacterium, different Clostridia and Candida. The alterations of the gut microbiota observed did not depend on the constipation status of RTT subjects while this microbiota produced altered SCFAs profiles potentially contributing to the constipation itself. Phenotypical and immunological characterizations of faecal fungal isolates from RTT subjects showed Candida parapsilosis as the most abundant species isolated in RTT, genetically unrelated to healthy controls’ isolates and with elevated resistance to azoles. Furthermore these isolates induced high levels of IL-10 suggesting increased tolerance and persistence within the host. Finally, the importance of multiple sequence alignment (MSA) accuracy in microbiome research was investigated comparing three implementations of the widely used NAST algorithm. By now, different implementations of NAST have been developed but no one tested the performances and the accuracy of the MSAs generated with these implementations. We showed that micca, a new bioinformatics pipeline for metataxonomics data improves the quality of NAST alignments by using a fast and memory efficient reimplementation of the NAST algorithm.

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6

Gorard, David A. "Intestinal motor function and the brain-gut axis in irritable bowel syndrome." Thesis, Imperial College London, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.395770.

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7

Bryant, Charlotte Elizabeth. "Dissecting the effects of sweet tastants in the human gut-brain axis." Thesis, University of Manchester, 2014. https://www.research.manchester.ac.uk/portal/en/theses/dieescting-the-effects-of-sweet-tastants-in-the-human-gutbrain-axis(9d71c67b-36c1-4cec-8df0-bf7d41b24476).html.

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The importance of nutrient induced gut-brain signalling in the regulation of human food intake has become increasingly apparent as the obesity epidemic progresses. Much of the caloric excess consumed comes from dietary sugars, but our knowledge about the mechanisms mediating the physiological and appetitive effects of sweet tastants in the gut-brain axis is far from complete. The comparative effects of natural sugars vs. artificial non-nutritive sweeteners are also poorly understood. Research in animal and cellular models has suggested a key role in the gut for the sweet taste receptors previously well described in the mechanisms of oral taste. The work presented in this thesis sought to answer key questions initially based on the hypothesis that gut sweet taste receptors also play a key role in the human gut-brain axis. The key aims were to elucidate i) whether sweet taste receptors in the gut contribute to the effects of sweet tastants in the human gut-brain axis, and ii) whether oral sweet taste modulates gut physiology and/or gut-brain signalling. Fifty-eight (36 males and 22 females) young (23.3 + 3.4 years) participants were recruited into four studies. All were healthy and generally lean (BMI 22.3 + 1.9). Key methodologies used included gastric emptying, appetite and satiety scores, food intake, blood hormone and glycaemic responses, and functional brain imaging. In chapter 3, a sweet taste receptor antagonist, lactisole, was used as a tool to investigate the role of gut sweet taste receptors in mediating the responses to glucose. However, lactisole had no impact on gastric emptying (a proxy measure of gut-brain signalling), blood glucose, gut hormones, appetite ratings or food intake. The data outlined in chapter four revealed that ingesting non-nutritive sweeteners, (aspartame, saccharin, and acesulfame-k) in combination with glucose did not enhance glycaemic responses or affect appetite ratings. However, the studies presented in chapter five demonstrated that the pattern and rate of gastric emptying of glucose very clearly differed depending on whether it was given orally or administered intragastrically. The interaction between oral and gastrointestinal sweet stimuli on brain activation was therefore investigated using functional brain imaging, and demonstrated that an oral pre-taste of glucose had a marked impact on subsequent brain responses to an intragastric glucose load. Effects were observed in homeostatic and non-homeostatic regions. These data offer little evidence that gut sweet taste receptors are important in humans: a non-taste pathway appears more likely to mediate the effects of glucose. However gut-brain signalling is markedly affected by oral sweet taste receptors. This has direct relevance for a better understanding of healthy human nutrition. Future studies need to investigate these interactions in more detail, using a wider panel of nutrients and tastants in health and disease.

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8

Rincel, Marion. "Role of the gut-brain axis in early stress-induced emotional vulnerability." Thesis, Bordeaux, 2017. http://www.theses.fr/2017BORD0870/document.

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Les maladies psychiatriques présentent de fortes comorbidités avec des désordres gastrointestinaux, ce qui suggère l’existence de bases physiopathologiques communes. Une littérature abondante démontre que l’adversité précoce (infection, stress) augmente la vulnérabilité aux désordres psychiatriques à l’âge adulte. Chez le rongeur, le modèle de séparation maternelle induit chez la descendance adulte des comportements hyperanxieux associés à une hypersensibilité au stress, ainsi que des dysfonctionnements de la sphère gastrointestinale. De plus, des études récentes rapportent une hyperperméabilité de la barrière intestinale chez les ratons soumis au stress de séparation, un effet conduisant potentiellement à une dysbiose et une perturbation de la communication intestin-cerveau. Le but de ma thèse était donc d’étudier le rôle de l’axe intestin-cerveau dans la mise en place des effets à long terme du stress précoce. Nos travaux récents ont montré que certains effets à long-terme de la séparation maternelle peuvent être atténués par l’exposition des mères à un régime hyperlipidique. Dans un premier temps, nous avons testé les effets du régime hyperlipidique maternel sur le cerveau et l’intestin de ratons soumis à la séparation maternelle. Nos résultats montrent que le régime maternel hyperlipidique protège de l’augmentation de la permeabilité intestinale induite par le stress. Nous avons ensuite testé le rôle causal de la perméabilité intestinale sur les comportements émotionnels à travers une approche pharmacologique et une approche génétique. Nous rapportons 1) que la restauration de la fonction barrière de l’intestin atténue certains effets de la séparation maternelle et 2) qu’une hyperperméabilité intestinale chez des souris transgéniques non soumises à un stress produit des effets similaires à ceux de la séparation maternelle. Enfin, nous avons examiné les effets d’une adversité précoce multifactorielle sur le cerveau et l’intestin (perméabilité et microbiote) chez la descendance adulte mâle et femelle dans un modèle combinant infection prénatale et séparation maternelle. Nos résultats mettent en évidence un effet sexe très marqué sur les phénotypes comportements et intestinaux. D’autres études sont nécessaires pour identifier les mécanismes sous-tendant les effets de la perméabilité et la dysbiose intestinale sur la vulnérabilité émotionnelle associée au stress précoce
Early-life adversity is a main risk factor for psychiatric disorders at adulthood; however the mechanisms underlying the programming effect of stress during development are still unknown. In rodents, chronic maternal separation has long lasting effects in adult offspring, including hyper-anxiety and hyper-responsiveness to a novel stress, along with gastrointestinal dysfunctions. Moreover, recent studies report gut barrier hyper-permeability in rat pups submitted to maternal separation, an effect that could potentially lead to dysbiosis and altered gut-brain communication. Therefore, the aim of my PhD was to unravel the role of the gut-brain axis in the neurobehavioral effects of early-life stress. We recently reported that some neural, behavioral and endocrine alterations associated with maternal separation in rats could be prevented by maternal exposure to a high-fat diet. We first addressed the effects of maternal high-fat diet on brain and gut during development in the maternal separation model. We show that maternal high-fat diet prevents the stress-induced decrease in spine density and altered dendritic morphology in the medial prefrontal cortex. Moreover, maternal high-fat diet also attenuates the exacerbated intestinal permeability associated with maternal separation. To explore a potential causal impact of gut leakiness on brain functions, we then examined the impact of pharmacological and genetic manipulations of intestinal permeability on brain and behavior. We report 1) that restoration of gut barrier function attenuates some of the behavioral alterations associated with maternal separation and 2) that chronic gut leakiness in naive adult transgenic mice recapitulates the effects of maternal separation. Finally, we examined the effects of multifactorial early-life adversity on behavior, gut function and microbiota composition in males and females using a combination of prenatal inflammation and maternal separation in mice. At adulthood, offspring exposed to early adversity displayed sex-specific behavioral (social behavior deficits in males and increased anxiety in females) and intestinal phenotypes. In conclusion, our work demonstrates an impact of gut dysfunctions, in particular gut leakiness, on the emergence of emotional alterations. Further studies are needed to unravel the role of the gut dysbiosis in the expression of the behavioral phenotypes associated with early-life adversity

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Sundman, Mark H., Nan-kuei Chen, Vignesh Subbian, and Ying-hui Chou. "The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease." ACADEMIC PRESS INC ELSEVIER SCIENCE, 2017. http://hdl.handle.net/10150/626124.

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As head injuries and their sequelae have become an increasingly salient matter of public health, experts in the field have made great progress elucidating the biological processes occurring within the brain at the moment of injury and throughout the recovery thereafter. Given the extraordinary rate at which our collective knowledge of neurotrauma has grown, new insights may be revealed by examining the existing literature across disciplines with a new perspective. This article will aim to expand the scope of this rapidly evolving field of research beyond the confines of the central nervous system (CNS). Specifically, we will examine the extent to which the bidirectional influence of the gut-brain axis modulates the complex biological processes occurring at the time of traumatic brain injury (TBI) and over the days, months, and years that follow. In addition to local enteric signals originating in the gut, it is well accepted that gastrointestinal (GI) physiology is highly regulated by innervation from the CNS. Conversely, emerging data suggests that the function and health of the CNS is modulated by the interaction between 1) neurotransmitters, immune signaling, hormones, and neuropeptides produced in the gut, 2) the composition of the gut microbiota, and 3) integrity of the intestinal wall serving as a barrier to the external environment. Specific to TBI, existing pre-clinical data indicates that head injuries can cause structural and functional damage to the GI tract, but research directly investigating the neuronal consequences of this intestinal damage is lacking. Despite this void, the proposed mechanisms emanating from a damaged gut are closely implicated in the inflammatory processes known to promote neuropathology in the brain following TBI, which suggests the gut-brain axis may be a therapeutic target to reduce the risk of Chronic Traumatic Encephalopathy and other neurodegenerative diseases following TBI. To better appreciate how various peripheral influences are implicated in the health of the CNS following TBI, this paper will also review the secondary biological injury mechanisms and the dynamic pathophysiological response to neurotrauma. Together, this review article will attempt to connect the dots to reveal novel insights into the bidirectional influence of the gut-brain axis and propose a conceptual model relevant to the recovery from TBI and subsequent risk for future neurological conditions.

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Lowe, Patrick P. "Inebriated Immunity: Alcohol Affects Innate Immune Signaling in the Gut-Liver-Brain Axis." eScholarship@UMMS, 2018. https://escholarship.umassmed.edu/gsbs_diss/987.

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Alcohol is a commonly consumed beverage, a drug of abuse and an important molecule affecting nearly every organ-system in the body. This project seeks to investigate the interplay between alcohol’s effects on critical organ-systems making up gut-liver-brain axis. Alcohol initially interacts with the gastrointestinal tract. Our research describes the alterations seen in intestinal microbiota following alcohol consumption in an acute-on-chronic model of alcoholic hepatitis and indicates that reducing intestinal bacteria using antibiotics protects from alcohol-induced intestinal cytokine expression, alcoholic liver disease and from inflammation in the brain. Alcohol-induced liver injury can occur due to direct hepatocyte metabolic dysregulation and from leakage of bacterial products from the intestine that initiates an immune response. Here, we will highlight the importance of this immune response, focusing on the role of infiltrating immune cells in human patients with alcoholic hepatitis and alcoholic cirrhosis. Using a small molecule inhibitor of CCR2/CCR5 chemokine receptor signaling in mice, we can protect the liver from damage and alcohol-induced inflammation. In the brain, we observe that chronic alcohol leads to the infiltration of macrophages in a region-specific manner. CCR2/CCR5 inhibition reduced macrophage infiltration, alcohol-induced inflammation and microglial changes. We also report that chronic alcohol shifts excitatory/inhibitory synapses in the hippocampus, possibly through complement-mediated remodeling. Finally, we show that anti-inflammasome inhibitors altered behavior by reducing alcohol consumption in female mice. Together, these data advance our understanding of the gut-liver-brain axis in alcoholism and suggest novel avenues of therapeutic intervention to inhibit organ pathology associated with alcohol consumption and reduce drinking.

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Choudhury, Sayantan Roy. "The Role Of Gut Microbiome In 3,4 Methylene Dioxymethamphetamine (MDMA) Mediated Hyperthermia In Rats." Bowling Green State University / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1530889852900613.

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12

PALADINO, Letizia. "THE GUT-BRAIN AXIS: EFFECTS OF THE PROBIOTIC LACTOBACILLUS FERMENTUM INTRODUCED IN THE DIET OF ETHANOL-FED MICE." Doctoral thesis, Università degli Studi di Palermo, 2022. https://hdl.handle.net/10447/563684.

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13

Dalliere, Nicolas. "Delineation of a gut brain axis that regulates context-dependent feeding behaviour of the nematode Caenorhabditis elegans." Thesis, University of Southampton, 2016. https://eprints.soton.ac.uk/388506/.

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Food directed behaviours execute key aspects of an animal’s ability to maintain a balanced energy intake. This homeostasis needs to integrate external cues that define the source and suitability of food and metabolic states that define requirements for food. In a human context, impairments in the mechanisms underlying feeding behaviours may result in maladapted responses that eventually lead to obesity and other metabolic diseases (e.g. bulimia and anorexia nervosa). Given the fundamental nature of this animal behaviour, simple invertebrate models can provide a route to facilitate understanding in higher animals and humans. In this study, the adaptive behavioural response of the nematode C. elegans to food is used to investigate the fundamental mechanisms underlying feeding behaviour. This utilized the behavioural transition of the worm’s feeding organ, the pharynx, during presentation and removal of food. Feeding behaviour was assayed in intact worms by counting the contraction-relaxation cycles of the pharynx. On food this shows a high pumping rate of around 250 pump.min-1 (ppm). In contrast, when transferred onto a no food arena, the pumping rate is reduced to almost zero. Subsequently, in the absence of food, the worms display a two phase adaptive pumping behaviour. The first ‘early phase’ has a slow increase of pumping rate up to ~30-40 ppm followed by a ‘late phase’ where the pumping rate becomes highly variable, fluctuating from very low (0-10 ppm) to high (100-150 ppm) values, and lasts at least up to 8 hours following the initial removal of food. Using this paradigm, I demonstrated that pumping behaviours were more than a simple ON/OFF switch but instead actively modulated by distinct neuronal circuits depending on the food context. Both non-peptidergic transmitters and neuropeptides are involved in the control of this adaptive response in a complex manner with the manner of regulation depending on the food context. For example, glutamate signalling stimulates pumping ‘on’ food while acting to reduce pumping in its absence. On food, the neurons M3 are known to increase the pumping rate via the release of glutamate. In this thesis, I have shown that a significant part of the glutamate associated with glutamatergic inhibitory tone in response to food removal is released from the pharyngeal neurons I2 and acts through the AVR-14 glutamate-gated chloride channel. In pharyngeal and central nervous system, shows no aberrant pumping behaviours, suggesting an important role for the worm’s enteric system. Genetic and environmental manipulation of sensory structures was used to address the modalities mediating the pumping behaviours. This analysis revealed that specific sensory structures and pathways are utilized in the distinct ‘on’ and ‘off’ food context. Strikingly, perception of odours from food by chemosensory neurons of the central nervous system does not contribute to the pumping rate as mutants in which the sensory functions of these neurons are deficient show no aberrant pumping behaviour in the presence of food. Rather mechanical cues seem important. The same chemosensory mutants show pumping rates off food that indicate they do not perceive food removal. This contrasts with the observation highlighted by RIP ablation and indicates that extrapharyngeal structures are involved but must be utilizing volume transmission. Investigation of the role of neurohormonal signalling was assessed by analysis of neuropeptide deficient and synaptic protein mutants. In egl-3 the pumping rate is totally abolished during food-deprivation. In contrast, unc-31 showed an elevated pumping rate ‘off’ food. These results suggest that neuropeptide signalling is required both to maintain the low level of pumping and to reduce it in the absence of food. Investigation of the role of individual neuropeptides supports the above. Interestingly both pharyngeally and extrapharyngeally expressed peptides support these phenotypes, consistent with a model in which food signals, involving discrete enteric and central nervous system, regulate the worm’s feeding behaviours. Overall, this thesis provides new insight into the neural substrates of behavioural plasticity in C. elegans. It shows that even a simple nematode with a nervous system of 302 neurons can show complex regulation of feeding behaviours, involving multiple pathways, which conceptually resonates with higher organisms’ organisation.

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Hoffman, Jared D. "THE PREBIOTIC INULIN BENEFICIALLY MODULATES THE GUT-BRAIN AXIS BY ENHANCING METABOLISM IN AN APOE4 MOUSE MODEL." UKnowledge, 2018. https://uknowledge.uky.edu/pharmacol_etds/24.

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Alzheimer’s disease (AD) is the most common form of dementia and a growing disease burden that has seen pharmacological interventions primarily fail. Instead, it has been suggested that preventative measures such as a healthy diet may be the best way in preventing AD. Prebiotics are one such potential measure and are fermented into metabolites by the gut microbiota and acting as gut-brain axis components, beneficially impact the brain. However, the impact of prebiotics in AD prevention is unknown. Here we show that the prebiotic inulin increased multiple gut-brain axis components such as scyllo-inositol and short chain fatty acids in the gut, periphery, and in the case of scyllo-inositol, the brain. We found in E3FAD and E4FAD mice fed either a prebiotic or control diet for 4-months, that the consumption of the prebiotic inulin can beneficially alter the gut microbiota, modulate metabolic function, and dramatically increase scyllo-inositol in the brain. This suggests that the consumption of prebiotics can beneficially impact the brain by enhancing metabolism, helping to decrease AD risk factors.

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15

Cobb, Christina. "A Link Between Gut Microbes & Depression: Microbial Activation of the Human Kynurenine Pathway." Scholarship @ Claremont, 2018. http://scholarship.claremont.edu/cmc_theses/1799.

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Our gut microbiota is involved in human development, nutrition, and the pathogenesis of gut disorders, but has more recently been implicated as a possible mechanism in the pathophysiology of several brain disorders, including disorders of mood and affect, such as depression. Researchers have referred to this dynamic, bidirectional signaling pathway between the gut and the brain as the “gut-brain axis.” However, most research on this axis has been limited to rodent studies, and there has been little insight into the mechanism behind it. I propose that the kynurenine pathway, where tryptophan is converted to kynurenine, is a compelling mechanism mediating the gut microbiota’s influence on depression. Kynurenine is a metabolite associated with depression, and this pathway has been shown to be manipulated through probiotic (Lactobacillus reuteri) consumption. I propose to study a probiotic intervention in humans, which would assess tryptophan metabolism along the kynurenine pathway by measuring metabolites downstream of this pathway. Urine, feces and blood samples would be collected from two groups, control and probiotic treatment, on day zero and day thirty. Colonic biopsies would be obtained on day thirty, and various analyses would be run to measure metabolite concentrations from the collected samples. The results from this study will help clarify a mechanistic connection between gut microbes and depression via the kynurenine pathway. Additionally, findings could indicate that a probiotic intervention has the ability to influence depressive behavior via a two-pronged approach originating from the kynurenine pathway.

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Farshim, Pamela Parastoo. "The impact of maternal weaning on behavioural development in rats: exploring the role of the gut-brain axis." Thesis, University of Surrey, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.665500.

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The complex mechanisms by which early life factors can impact the developing mammalian system remain largely unclear. Animal studies have led to the identification of neurotransmitter systems that are influenced through manipulation of early life conditions. In addition, evidence suggests that early life events can influence signaling through the gut-brain axis to modulate brain function and behaviour. Specifically, the functions of the host gut microbiota and metabolism have been highlighted. Weaning and stress have both been shown to influence the development of central neurotransmitters implicated in emotional regulation. This thesis applied a multidisciplinary approach to investigate the effect of delayed weaning and its modulation by stress upon host development at multiple tiers of biological organisation. These included behavioural, neurochemical, gut microbial and metabonomic studies. Animal behavioural studies demonstrated that a lack of weaning at the standard age of 21 days in rats, leads to a marked 'depressive-like' phenotype. Furthermore, receptor autoradiography revealed non-weaned animals to exhibit altered oxytocin receptor binding in the amygdala and different stress coping mechanisms. Fluorescence in situ hybridisation studies exposed significant weaning and stress-induced effects upon gut microbiota composition. In addition, NMR-based metabonomic studies illuminated fluctuations in a number of endogenous and host-microbial co-metabolites known to be implicated in mood and stress-related disorders. Collectively, the results show that early life factors such as weaning and stress are able to have a marked influence on behavioural development. The findings highlight that signaling through the gut-brain axis may modulate behavioural development possibly through the production of neuroactive metabolites at critical stages of development and open new areas of investigation. The findings identify novel targets for interventions in the pathogenesis of paediatric neuropsychiatric disorders.

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Cassie, Nikki. "The impact of macronutrient content and food structure on the gut-brain axis in the regulation of satiety." Thesis, University of Aberdeen, 2016. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=230578.

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Enhancing satiety may be a route to overcome excess food intake, a causative agent of the obesity epidemic effecting [sic] developed and developing nations. A theory has evolved that if food processing has been a major contributor to the obesity epidemic then food processing and manipulation could be the solution to the crisis. This could be by means of the manipulation of food to target regulatory mechanisms of the food-gut-brain axis to produce satiety from fewer calories. This thesis is an investigation, using the Sprague Dawley rat model, into possible interactions between macronutrient content and food structure in the regulation of satiation and satiety, and to provide evidence for possible enhanced satiation or satiety by protein crosslinking noted in human studies. Three principle studies were performed: 1) variation in macronutrient content of a base diet presented in a solid or liquid form; 2) gavage of a single macronutrient containing solutions directly to the stomach; and 3) using protein crosslinking to change food form without changing caloric density. Overall, the study found no evidence to support an interaction between macronutrient content and diet form, nor that protein is a more effective macronutrient for inducing satiation or prolonging satiety. The analysis did identify that liquid diets can increase satiation, but can result in negative homeostatic effects and excess food consumption. Research exploring the use of protein crosslinking to promote satiation is still at an early stage but the findings presented in this thesis identify utilisation as a potential tool for enhanced satiation. These studies suggest that while protein crosslinking may enhance satiation there is no translation into longer term satiety. Nevertheless, these findings serve as a basis for further research and could provide information to the food industry for the development of food products that increase the satiation and satiety properties of food.

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Osman, Aya. "The impact of milk caseins on behavioural development in rats : exploring the role of the gut brain axis." Thesis, University of Surrey, 2018. http://epubs.surrey.ac.uk/846301/.

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Exposure to milk caseins beyond the normal weaning age in rats (21 days) was shown to impact the development of the opioid system, a key player in emotional regulation. Further, milk alters the gut microbiome and evidence suggests the gut microbiota can modify brain function and behaviour. Given such evidence, it is hypothesised exposure to milk casein and its bioactive breakdown product, beta casomorphin-7 (BCM-7) beyond weaning age in rats results in disruptions to brain neurochemistry and behaviour via a microbiome-gut-brain axis mechanism. This work aimed to investigate this hypothesis using in vivo behavioural, neurochemical, gut microbial and metabonomic studies. The behavioural results showed that exposure to casein from postnatal day 21-26 resulted in an increase in ‘depressive-like’ behaviour as measured by the forced swim test (FST) and that BCM-7 is not the only casein derived product driving such behavioural impairments. Quantitative autoradiography revealed the casein induced depressive phenotype was concomitant with changes to oxytocin and opioid receptors in regions of the brain associated with mood. Fluorescence in situ hybridization showed an increase in Clostridium Histolyticum in the gut suggesting a microbiome-gut-brain axis role in the casein induced changes reported. In line with this, antibiotic knock-down of gut microbial activity not only prevented the development of the casein induced depressive phenotype, but also caused a casein independent antidepressive-like effect as assessed by the FST. Lastly, metabonomic analysis revealed an increase in gut microbial metabolites and disruptions to choline and energy metabolism in response to prolonged casein exposure, which have been implicated in mood disorders. Collectively, these findings suggest casein exposure beyond weaning age results in neurochemical and emotional impairments via a potential microbiome-gut-brain axis mechanism. This indicates that prolonged breastfeeding periods may cause mood disorders in humans and highlight the need for more comprehensive guidelines regarding an appropriate weaning age.

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19

Murray, Emma. "Immune Challenge During Puberty: Role of the Gut Microbiota and Neurobehavioural Outcomes." Thesis, Université d'Ottawa / University of Ottawa, 2020. http://hdl.handle.net/10393/40467.

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Puberty is a critical period of development characterized by rapid physiological changes and significant brain reorganizing and remodeling. These rapid changes render the developing brain particularly vulnerable to stress and immune challenge. In mice, exposure to an immune challenge (lipopolysaccharide; LPS) during puberty causes enduring effects on stress reactivity, cognitive functioning, and depression- and anxiety-like behaviors later in life. However, the mechanisms underlying these effects are unknown. The gut microbiome can profoundly influence the immune system. There is also close bidirectional communication between the gut microbiome and the central nervous system (CNS) through neural, endocrine and immune signaling pathways, which can alter brain chemistry and emotional behaviour. Thus, we hypothesized that altering microbial composition during puberty could mitigate acute immune responses and prevent enduring outcomes later in life. The current thesis examined the effect of gut manipulation with probiotics during puberty on LPS-induced immune responses and enduring anxiety- and depression-like behaviours, and stress-reactivity in adulthood, in male and female CD1 mice (Article 1). Next, we examined age and sex differences in gut microbial composition before and after exposure to an immune challenge. We also examined the effects of consuming a single strain probiotic bacterium (Lactobacillus Reuteri) during puberty on the immune response and the long-term changes in memory, anxiety-like behavior, and stress reactivity in adulthood (Article 2). Lastly, we examined how microbial colonization between pubertal and adult mice can alter acute peripheral and central inflammatory responses to LPS (Article 3). The current dissertation has addressed sex-specific vulnerabilities to an immune challenge during pubertal development and the moderating influence of the gut microbiome. These studies have demonstrated that manipulating the gut microbiome during puberty can mitigate acute immune responses and prevent enduring neurobehavioural outcomes later in life.

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20

Lebovitz, Yeonwoo. "Modulation of Neurodevelopmental Outcomes using Lactobacillus in a Model of Maternal Microbiome Dysbiosis." Diss., Virginia Tech, 2019. http://hdl.handle.net/10919/94328.

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Neurodevelopmental disorders, such as autism spectrum disorders, schizophrenia, and attention deficit hyperactivity disorder, are a heterogeneous set of developmental disorders affecting the central nervous system. Studies into their etiology remain challenging, as neurodevelopmental disorders frequently present with a wide range of biological, behavioral, and comorbid symptomologies. Increasing epidemiological reports of antibiotic use during pregnancy as a significant correlate of subsequent mental disorder diagnosis in children suggest a mechanism of influence via the maternal gut-fetal brain axis. Importantly, antibiotics cause dysbiosis of the gut microbiome and disrupt the delicate composition of the microbial inoculum transferred from mother to child, which is critical for development of the immune system and holds implications for long-term health outcomes. The research objective of this dissertation is to reveal a causal mechanism of maternal microbial influence on neurodevelopment by examining the brain's resident immune cells, microglia, and corresponding behavioral outcomes in a mouse model of antibiotics-driven maternal microbiome dysbiosis (MMD). We identify early gross motor deficits and social behavior impairments in offspring born to MMD dams, which paralleled hyperactivated microglia in brain regions specific to cognition and social reward. The MMD microglia also exhibited altered transcriptomic signatures reflective of premature cellular senescence that support evidence of impaired synaptic modeling found in MMD brains. We report that these deficits are rescued in the absence of Cx3cr1, a chemokine receptor expressed ubiquitously on microglia, to highlight a pathway in which maternal microbiota may signal to neonatal microglia to undergo appropriate neurodevelopmental actions. Finally, we characterize Lactobacillus murinus HU-1, a novel strain of an important gut bacterium found in native rodent microbiota, and demonstrate its use as a probiotic to restore microglial and behavioral dysfunction in MMD offspring.
Ph. D.
Population studies on neurodevelopmental disorders, such as autism spectrum disorders, schizophrenia, and attention deficit hyperactivity disorder, highlight antibiotic use during pregnancy as a major correlate of subsequent diagnoses in children. These findings support a growing body of evidence from animal and human studies that the microbial ecosystems (“microbiome”) found in and on our bodies play significant roles in mental health, including mood, cognition, and brain function. Importantly, antibiotics during pregnancy create an imbalance of the gut microbiome (“dysbiosis”) and disrupt the microbial inoculum transferred from mother to child, which is critical for maturation of the infant immune system and holds implications for long-term health outcomes. Thus, the research objective of this dissertation is to identify a mechanism of influence from the mother’s gut to the neonate’s brain by examining the brain’s resident immune cells (“microglia”) in a mouse model of antibiotics-driven maternal microbiome dysbiosis (MMD). We uncover autism-like behavioral deficits and dysfunctional microglia in MMD offspring, and characterize signaling cues specific to microglia by which improper neurodevelopment may be taking place. We also reveal that the detrimental effects of MMD are reversed in mice born to mothers pretreated with a probiotic candidate, Lactobacillus murinus HU-1, to suggest maternally-derived Lactobacillus may help to mediate proper neurodevelopment.

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Ahlbin, Rebecca, and Tara Junker. "”Gut-brain axis” : En kvantitativ undersökning om konsumenters kännedom om och attityd till livsmedel som främjar tarmfloran och dess kommunikation medhjärnan." Thesis, Uppsala universitet, Institutionen för kostvetenskap, 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-359922.

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Bakgrund: Ett intresse hos konsumenter för mat kopplat till tarmfloran har setts av Livsmedelsverket. Fenomenet gut-brain axis har nyligen fått acceptans i forskarvärden. Sambandet mellan mage, tarm och psyket tyder på att gut-brain axis har inflytande på humör samt beteende. Syfte: Undersöka individers kännedom om och attityd till tarmflora och gut-brain axis med fokus på mental hälsa samt om konsumenter är villiga att välja livsmedel med betydelse för tarm- och mental hälsa. Metodbeskrivning:´Webbenkät delades via sociala medier. Frågorna gällde främst konsumenters attityd och kännedom kring tarmfloran. Svaren redovisas i figurer och tabeller. Chi-två tester i SPSS har genomförts. Resultat: 493 enkätsvar. Majoriteten av respondenterna har kännedom om en dubbelriktad kommunikation mellan hjärna och tarm. Kännedomen om begreppet gut-brain axis var låg, men det finns ett samband mellan kännedom om begreppet och utbildningsnivå samt ålder. Majoriteten hade kännedom om sambandet mellan kost, tarmflora och mental hälsa. Skepsis fanns beträffande livsmedel som marknadsfördes med påståendena “balanserar din tarmflora” respektive “förbättrar ditt mentala välmående” med lägre positiv attityd till påståendet om mentalt välmående. Slutsats: Den dubbelriktade kommunikationen mellan tarmen och hjärnan, samt den mentala hälsan, är bekant för konsumenten, dock inte begreppet gut-brain axis. Attityden till livsmedel med påståenden gällande tarmflora kopplat till mental hälsa är negativ. Kännedomen är fortfarande liten vad gäller fackbegrepp, men det finns stort intresse för att medvetet äta mat som balanserar tarmfloran. Vetenskaplig information gällande tarmfloran bör i framtiden på ett lätt sätt kommuniceras i större utsträckning till konsumenterna.

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Andersson, Jonas. "Is there a Connection Between the Gut-Microbiota and Major Depression?" Thesis, Högskolan i Skövde, Institutionen för biovetenskap, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-19150.

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Major depressive disorder (MDD) is rapidly growing and one of the most common causes of disability and mortality worldwide. People with MDD often display brain changes such as adisrupted balance in neurotransmitters, impaired neurogenesis and neuroplasticity. Traditionally has MDD been treated with medications and talking therapies (psychotherapy). Studies have shown that just around 50 % of people with MDD get improvements from common traditional treatments.Therefore is there a great need for a better understanding of MDD and new treatments. There is now an emerging field of research that indicates that the gut microbiota plays a crucial role in disturbing normal brain functioning in MDD. This connection between the gut and the brain is called the gutbrain axis.The thesis aims to investigate if there is a connection between gut microbiota disruption and MDD and if gut microbiota restoration can be a potential effective future treatment for MDD. Key findings of the thesis were, studies show that people with MDD often display gut microbiota disruption and chronic low grade inflammation. Studies also indicate that this inflammation can cause the specific brain change often displayed in people with MDD. One of the most critical findings in the thesis was that gut brain treatments affect tryptophan metabolism, which affects the risk of MDD. The research area of the gut brain axis is still new and many more studies are needed,particularly in humans.

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23

Lisko, Daniel Joseph. "The Effect of Probiotics on Human Gastrointestinal Microbial Communities." Youngstown State University / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ysu1442437599.

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24

Marsilio, Ilaria. "Functional and Molecular Studies of the Crosstalk between Intestinal Microbioma and Enteric Nervous System and Potential Effects on the Gut-Brain Axis." Doctoral thesis, Università degli studi di Padova, 2019. http://hdl.handle.net/11577/3427312.

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L'interazione fra costituenti della parete intestinale e microflora commensale costituisce il principale artefice del mantenimento della barriera mucosale, della promozione dello sviluppo del tratto gastrointestinale (GI) e della modulazione delle funzioni GI. In questo contesto, giocano un ruolo chiave i recettori Toll-like (TLRs), un sistema di proteine che attivano la risposta immunitaria innata e assicurano l'integrità funzionale e strutturale del SNE. In questo studio sono state caratterizzate le alterazioni strutturali e funzionali del SNE murino indotte da: i) cambiamenti nel segnale dell’immunità innata, mediato dal recettore TLR4, ii) una miscela di fosfolipidi ossidati (OxPAPC), implicati nel blocco del segnale generato dai recettori TLR2 e TLR4 e iii) anomalie nella composizione del microbiota. Data l’importanza di un corretto segnale TLRs-dipendente nel mantenimento della rete nervosa e del codice neurochimico del SNE, segmenti di ileo provenienti da topi WT e TLR4-/- hanno evidenziato anomalie nell’attività contrattile neuromuscolare associate ad un’eccessiva modulazione inibitoria da NO ed ATP, a sostegno della presenza di un dialogo tra TLR4, SNE e microflora, fondamentale per la modulazione della funzione neuromuscolare. Studi strutturali su preparati di ileo di topi TLR4-/- evidenziano un’alterata architettura del SNE a livello gliale, indicando un coinvolgimento del recettore TLR4 nel mantenimento dell'integrità della rete gliale enterica mediato dalla produzione di ATP e della trasmissione purinergica evidenziano il ruolo di TLR4 nell’omeostasi strutturale e funzionale del SNE. Inoltre, è stato dimostrato che la mancanza del recettore TLR4 determina nell’ippocampo, come a livello del SNE, una compromessa neuroplasticità caratterizzata da alterazioni nella densità neuronale associata a variazioni della distribuzione della rete gliale, a confermare un ruolo fondamentale del segnale TLRs anche a livello centrale. In parallelo, è stato indagato il ruolo del segnale mediato dai TLRs nell’asse microbiota-TLRs-SNE, tramite la somministrazione in acuto con OxPAPC, inibitore del segnale mediato da entrambi i recettori TLR2 e TLR4, in topi adolescenti (3 ± 1 settimane). Il trattamento con OxPAPC ha causato un’alterazione significativa della risposta neuromuscolare associata a modifiche della rete neuro-gliale del SNE, confermando l’importanza del segnale mediato da tali recettori nell'assicurare l’integrità funzionale e strutturale del SNE durante l'adolescenza. Recenti studi riportano un ruolo primario nel dialogo tra i recettori TLRs e il sistema serotoninergico ed è stato evidenziato come OxPAPC comporti iperesponsività alla serotonina, alterazioni nella distribuzione recettoriale serotoninergica associata a variazioni nel metabolismo del triptofano, a sostegno della presenza di un dialogo tra immunità innata e sistema serotoninergico. Al fine di approfondire il ruolo dell'asse microbiota-intestino nell’omeostasi del SNE è stato messo a punto un modello animale di deplezione di microbiota intestinale attraverso la somministrazione di 4 antibiotici a topi adolescenti. Tale trattamento ha determinato un fenotipo simil germ-free ed alterazioni della motilità intestinale e dell'integrità della rete neuronale e gliale enterica. Data l’importanza di una corretta composizione del microbiota commensale nel mantenimento del codice neurochimico del SNE che nella produzione di neurotrasmettitori a livello enterico, sono state studiate le vie di neurotrasmissione coinvolte nella sensibilità viscerale. Un’alterata composizione del microbiota intestinale altera la sensibilità viscerale associata anomalie nella risposta neuromuscolare alla serotonina accompagnate da una compromessa rete recettoriale serotoninergica e del metabolismo del triptofano, sottolineando l’importanza di una corretta composizione del microbiota nel mantenimento delle funzioni mediate dal sistema serotoninergico.

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Rees, Joanna. "Diet quality and mental health: How does improved cooking confidence after a food literacy cooking program affect mental health outcomes and associations with dietary and gut biomarkers of the gut-brain axis?" Thesis, Edith Cowan University, Research Online, Perth, Western Australia, 2022. https://ro.ecu.edu.au/theses/2497.

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The prevalence and burden of obesity and mental health disorders have increased in recent years. Better understanding of their relationship is required to identify modifiable risk factors to direct future interventions for improved health outcomes. In Australia dietary patterns have shifted away from home-cooked nutritious foods, towards reliance on pre-prepared convenience meals which are typically energy-dense, nutrient-poor. Latest statistics reflect a decline in diet quality, with significant barriers to healthier eating featured in the living environment. A healthy diet is central to lowering the risks of metabolic disease and for the protection of mental health. The global effort to tackle obesity and improve knowledge around cooking and eating behaviour is gaining momentum. In parallel, tremendous advances have occurred in gut microbiome research, highlighting the intricate relationship between the gut microbiota and human health. Diet directly affects microbiome composition, and food-based microbially-derived metabolites play a pivotal role in human physiology that are correlated with multiplicitous diseases including mental illness. This study examined the links between fruit and vegetable intake, diet quality and mental health. Then followed an evaluation of effects of a community-based cooking program on cooking confidence and ability to overcome barriers to healthy eating. Finally, the associations between cooking confidence, dietary and gut biomarkers, the gut microbiome and mental health were investigated. Part one of this PhD involved the creation of a dietary fibre, resistant starch and polyphenolic phytochemical database with which to estimate amounts of these important nutrients in everyday Australian foods. In Part two the database was applied to the pre-collected data from a large cohort of Australian adults, to explore associations between fruit and vegetable intake and mental health after 5 years. Parts three and four studied participants of a 7-week cooking program. Part three comprised evaluation of the program on cooking confidence, ability to overcome barriers to healthy eating, dietary intake and mental health post-program. Part four involved an investigation of the relationship between diet quality, mental health, dietary and gut biomarkers, including the novel inclusion of bile acids, the gut microbiome and underlying mechanisms of the gut-brain axis. Microbiome-specific dietary components positively affected mental health outcomes. The 7-week cooking program overcame some barriers to healthy eating and increased cooking confidence and mental health but did not change diet quality or dietary and gut biomarkers associated with the gut-brain axis. Bile acids significantly contributed to microbial variance as did dietary fibre derived from fruit and cereals and grains. Diet quality and BMI were associated with gut biomarkers and microbiome composition, and phylum level microbial diversity significantly decreased for those in the lowest diet quality category. Additionally, there were iii diet-driven shifts in the relative abundance of predominant phyla that have been linked to poorer mental and physical health outcomes. Our understanding of the diet-gut microbiome-mental health connection is still emerging but there is mounting evidence that diet quality has a profound effect and presents a key modifiable risk factor in the protection against poor health due to both physiological and neurological processes via the gut-brain axis.

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Eckered, Göransson Sara. "Kan probiotika lindra depression?" Thesis, Linnéuniversitetet, Institutionen för kemi och biomedicin (KOB), 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-84831.

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Tidigare forskning har visat ett samband mellan vår tarmflora och vår fysiska hälsa, och idag görs även mycket forskning på om den även kan påverka vår mentala hälsa. Idag lider över fyra procent av världens befolkning av depression, och den här litteraturstudien har, genom att analysera sju studier och deras resultat, försökt få svar på frågan om probiotika kan lindra depression. Antingen som primär behandling eller som komplement till annan behandling. Den här litteraturstudien gav inga konkreta svar på den frågan, annat än att alla inblandade forskare är överens om att det behövs göra fler, längre och större studier innan man kan dra några slutsatser.
Previous research has shown a connection between our microbiota and physical health, and today a lot of research is also being done on whether it also can affect our mental health. Today, over four percent of the world's population suffers from depression, and this literature study has, by analysing seven studies and their results, attempted to answer the question of whether probiotics can alleviate depression. Either as primary treatment or as a supplement to other treatment. This literature study did not provide any definite answers to that question, other than that all the researchers involved in the studies analysed agree that more, longer and larger studies are needed before one can draw any conclusions.

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Nilsson, Malin. "Effects of the Mediterranean Diet on Brain Function : Underlying mechanisms." Thesis, Högskolan i Skövde, Institutionen för biovetenskap, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-17531.

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The Mediterranean diet (Medi) has been highlighted as the golden diet rich in protective properties associated with cognitive- and emotional health. The foundation of the Medi comprises vegetables, fruits, nuts and seeds, legumes, and extra virgin olive oil. Research has been conducted in both holistic dietary approach and single nutrient approach regarding the impact of nutrition and diet, in this case, the Medi‟s effect on brain health. This review aims to give an up to date overview of the Mediterranean diet, outline some of the diet's abundant nutrients, and discuss studies linking the nutrient's potential effect on depression, cognitive decline, dementia, and brain structure and function. In addition, this review will attempt to assess whether the Medi as a whole or if a single nutrient approach is accountable for the health-promoting findings. Furthermore, the gut-brain axis, and other potential underlying mechanisms involved in the modulation of food- and nutrient intake and their effects on the brain, will be outlined. A diet high in fruit-, vegetable-, polyunsaturated fatty acid-, and monounsaturated fatty acid content has great power for health-maintenance and decreases the risk of suffering cognitive decline, dementia, and potentially depression. More randomized controlled trials are however eagerly awaited to give more substance to previous findings.

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Lauffer, Adriana. "Efeito do estresse agudo, crônico e ambos combinados na permeabilidade intestinal de ratos." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2015. http://hdl.handle.net/10183/143409.

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Introdução: o estresse psicológico aumenta a permeabilidade intestinal em roedores e humanos, potencialmente levando a inflamação de baixo grau e aos sintomas em distúrbios gastrintestinais funcionais. No entanto, o efeito do estresse agudo combinado ao estresse da vida crônica, que mimetiza potencialmente melhor a situação humana, é desconhecido. Além disso, há poucos dados disponíveis sobre os efeitos do estresse em intestino delgado versus cólon. Métodos: ratos Wistar foram alocados em quatro protocolos de estresse: 1/ controles; 2/ estresse agudo (isolamento e movimentos limitados); 3/ Crowding stress:crônico e 4/ estresse agudo + estresse crônico. Amostras de jejuno e cólon foram colhidas para estudar a permeabilidade em câmaras deUssing, a expressão gênica de moléculas de junção firmes e a densidade de mastócitos. Níveis de corticosterona no plasma foram medidos. Principais resultados:corticosterona plasmática foi avaliada nas três condições de estresse, teve níveis mais altos na condição de estresse combinado. Permeabilidade do jejuno foi aumentada em todas as condições de estresse e correlacionada com os níveis de corticosterona. O aumento da expressão das claudinas 1, 5 e 8, daocludina e da ZO-1 foi detectado no estado de estresse agudo no jejuno. Em contraste, a permeabilidade do cólon foi aumentada no protocolo de estresse combinado, e a expressão de moléculas das junção firmes permaneceu inalterada. O aumento da densidade de mastócitos foi observado no cólon nos ratos submetidos aos estresses crônico e combinado. Conclusão e inferências:os estresses agudo, crônico e combinado influenciam diferentemente a permeabilidade intestinal, a expressão de moléculas de junção firmes e a atividade dos mastócitos, no jejuno e no cólon. Estes resultados fornecem uma visão mais aprofundada dos mecanismos de hiperpermeabilidade intestinal relacionadas ao estresse.
Background: Psychological stress increases intestinal permeability in rodents and humans, potentially leading to low-grade inflammation and symptoms in functional gastrointestinal disorders through disturbances in brain-gut axis. However, the effect of acute stress on the background of Crhonic life stress, potentially better approaching the human situation, is unknown. Moreover, only limited information is available on the effects in small intestine versus colon in animal model. Methods: Wistar rats were allocated to 4 stress protocols: 1/ sham; 2/ acute stress (isolation and limited movement); 3/ Crhonic crowding stress and 4/ acute + Crhonic stress (n = 8 per group). Jejunum and colon were harvested to study permeability in Ussing chambers, gene expression of tight junction molecules and mast cell density. Plasma corticosterone levels were measured. Key Results: Plasma corticosterone was elevated in all three stress conditions, with the highest levels in the combined stress condition. Permeability of the jejunum was increased in all stress conditions and correlated with corticosterone levels. Increased expression of claudin 1, 5 and 8, occludin and ZO-1 was detected in the acute stress condition in the jejunum. In contrast, colonic permeability was increased in the acute on Crhonic stress protocol only and the expression of tight junction molecules was unaltered. Increased mast cell density was observed in the Crhonic and acute on Crhonic stress condition in the colon only. Conclusion and Inferences: Acute, Crhonic and combined stress differentially affect intestinal permeability, expression of tight junction molecules and mast cells in the jejunum and the colon. These findings provide further insight in the mechanisms of stress-related intestinal hyperpermeability and barrier.

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Charton, Elise. "Lait humain vs. préparation pour nourrissons : digestibilité des protéines et impact sur l’axe microbiote-intestin-cerveau." Electronic Thesis or Diss., Rennes, Agrocampus Ouest, 2023. http://www.theses.fr/2023NSARB368.

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Une majorité de nourrissons reçoivent encore aujourd’hui des préparations pour nourrissons (PPN), fabriquées à base de lait bovin et soumises à de nombreux traitements technologiques. Ces substituts ont pour but de mimer au mieux le lait humain (LH). Cependant, malgré l’évolution des PPNs, des différences persistent entre le LH et les PPNs en termes de composition et structure, et effets sur le développement et la santé à court et long termes du nourrisson et adulte en devenir. L’objectif de ce travail était de comprendre comment la nature de l’alimentation infantile, LH vs. PPN, modulait la digestibilité protéique et, plus globalement, comment elle influençait l’axe microbiote intestin-cerveau. Deux modèles du nourrisson humain ont été utilisés et comparés, le mini-porc Yucatan entre 16 et 21 jours de vie, et un modèle de digestion in vitro dynamique paramétré pour mimer le nourrisson à terme. Les contenus digestifs et tissus ont ensuite été analysés via des approches métagénomique (microbiote), histologique et de perméabilité ex vivo (physiologie intestinale), d’expression génique et de métabolomique ciblée (intestin, cerveau et plasma). Les résultats ont montré que la digestibilité de l’azote total et dans une moindre mesure, celle de certains acides aminés (Lys, Phe, Thr, Val, Ala, Pro et Ser) différaient entre LH et PPN. Les deux modèles de digestion (in vivo et in vitro) étudiés ont conduit à des résultats similaires en termes de déstructuration des aliments et du taux de protéines intactes résiduelles en phase gastrique. Le modèle de digestion in vitro dynamique utilisé ici est donc un bon outil de prédiction de la digestion in vivo. L’axe microbiote-intestin-cerveau et notamment la composition du microbiote, ainsi que le métabolisme du tryptophane, malgré une digestibilité similaire entre aliments, étaient modulés différemment par le LH et la PPN. L’augmentation de la permeabilité intestinale, bien que modérée, était associée à un renforcement du système immunitaire mucosal avec le LH. Ces modifications sont associées à des changements d’expression génique (fonctions barrière et endocrine, récepteurs aux AGV) aux niveaux hypothalamique et striatal, et de profils métaboliques principalement aux niveaux hippocampique et plasmatique. Certains composants présents dans le LH (ex.: oligosaccharides, azote non protéique tel que l’urée, consortium bactérien) et absent dans la PPN peuvent expliquer ces résultats. La supplémentation des PPNs en ces composants bioactifs et/ou la modulation de la fraction protéique pourraient être des leviers pour l’optimisation des PPNs
Nowadays, a high rate of infants is still being fed infant formulas (IF) based on cow milk and subjected to several technological treatments. These substitutes aim to mimic as close as possible the human milk (HM). Despite of IF improvement, differences still exist between HM and IF in terms of composition and structure, and effects on health in infancy, and later on in adulthood. The objective of this work was to understand how the infant food modulated the dietary nitrogen digestibility and, in overall, how it shaped the microbiota-gut-brain axis. Two infant models were used and compared, the 16 to 21-day-old mini-piglet Yucatan and an in vitro dynamic digestion model parametered with term infant digestive conditions. Digestive contents and tissues were then analyzed using metagenomic (microbiota), histological and ex vivo permeability (intestinal physiology) approaches, gene expression and targeted-metabolomic approaches (intestine, brain and plasma). The results showed that the digestibility of nitrogen and at least extent, that of a few amino acids (Lys, Phe, Thr, Val, Ala, Pro and Ser) were different between HM and IF. The two digestion models (in vivo and in vitro) led to similar observations in terms of meal deconstruction and proteolysis, showing that the in vitro dynamic digestion model is a good proxy of the in vivo digestion regarding digestion kinetics. The microbiota-gut-brain axis, notably regarding the colonic microbial composition and the tryptophan metabolism, which digestibility was similar between infant foods, were differently modulated by HM and IF. The increase of the intestinal permeability, though moderately, was associated with a boost of the intestinal immune system and changes in gene expression (barrier and endocrine functions, volatile fatty acids receptors) at hypothalamic and striatal levels and with changes in hippocampal and plasma metabolomic profiles. Some components present in HM (e.g.: oligosaccharides, non-protein nitrogen such as urea, bacteria consortia) and absent in IF can explain the discrepancies observed. IF-supplementation with these bioactive components and/or with the modulation of the protein profile would be of interest for further investigation

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Delaere, Fabien. "Détection des nutriments et contrôle central de la prise alimentaire." Thesis, Lyon 1, 2009. http://www.theses.fr/2009LYO10269.

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En relation avec sa position anatomique, la détection portale de nutriments se situe au coeur de l’impact de la composition nutritionnelle d’un repas sur la prise alimentaire et le métabolisme énergétique. Ainsi, la détection portale de glucose, produit par exemple en réponse aux protéines alimentaires, induit un signal nerveux à l’origine d’une induction de la satiété et d’une amélioration de l’homéostasie glucidique. Grâce à des travaux physiologiques et anatomiques chez le rat, nous proposons un modèle pour cette détection dans lequel deux modes interviennent, soit un transport et un catabolisme intracellulaire, soit une détection purement extracellulaire du glucose. La glycémie portale est détectée par l’un ou l’autre de ces mécanismes en fonction de sa différence avec la glycémie artérielle, reflet du statut nutritionnel et métabolique des individus. Un signal nerveux est ensuite initié dans les neurones périportaux, dont les axones aboutissent à proximité de la lumière veineuse. Les études immunohistochimiques réalisées ont permis de montrer que ce signal induit une activation cérébrale étendue en relation avec les effets multiples du glucose portal, dans le tronc cérébral, les systèmes sensoriels et cortico-limbiques, et l’hypothalamus. Dans ce dernier, la nature cellulaire de l’activation conforte notamment l’hypothèse de l’implication du signal glucose portal dans l’effet de satiété induit par les régimes riches en protéines
Nutrient sensing in the portal vein occurs in a strategic location to relay the effects of the diet on food intake and energy metabolism. The portal sensing of glucose produced for instance in response to dietary proteins initiates a nervous signal that ultimately induces satiety and a better control of glucose metabolism. Our physiological and anatomical approaches enable us to propose a sensing model in which two different mechanisms can occur, involving either the intracellular transport and catabolism of glucose or a direct extracellular detection. Portal glycaemia is detected by one pathway or the other depending on its difference with arterial blood glucose, which reflects the nutritional and metabolic state of the subject. A nervous signal is then initiated in periportal neurons, whose axons terminate close to the venous lumen. Our immunohistochemical studies have shown that this signal induces a widespread activation in the brain that relates to the multiple effects of portal glucose appearance, in the brainstem, the sensory and cortico-limbic systems and the hypothalamus. In this latter area, the cellular nature of the activation supports the hypothesized central role of portal glucose appearance in the satiety effect of high-protein diets

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Dupin, Alice. "Insular Cortex neurons projecting to the vagal complex : characterization and roles in behavior and inflammation." Electronic Thesis or Diss., Sorbonne université, 2024. http://www.theses.fr/2024SORUS192.

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Les interactions entre le cerveau et le reste du corps sont cruciales pour la survie de l'organisme. Le cerveau reçoit et intègre une multitude d'informations externes et internes et régule diverses fonctions physiologiques en permanence. Notamment, le système nerveux interagit étroitement avec le système immunitaire. En cas d'infection, les caractéristiques uniques du cerveau permettent une régulation optimisée des réponses immunitaires. Cela inclut la capacité du cerveau à détecter les signaux environnementaux, à anticiper les situations à venir et à transmettre rapidement des signaux à travers un vaste réseau de neurones innervant l'ensemble du corps en quelques millisecondes. Le nerf vague, reliant le cerveau aux organes viscéraux, est un support important de cette communication bidirectionnelle. Il est composé de branches sensorielles et motrices. Les afférences relaient les informations périphériques au complexe vagal dans le cerveau, qui transmet les signaux aux structures cérébrales plus profondes, tandis que les efférences motrices transmettent les réponses générées vers les organes cibles. Dans le traitement des informations intéroceptives, le cortex insulaire émerge comme un hub multimodal essentiel. En tant que cortex sensoriel, il reçoit diverses entrées des systèmes de détection externes tels que les cortex somatosensoriels et olfactifs, tout en étant densément interconnecté avec les régions comme le complexe vagal, traitant les signaux internes tels que les stimuli inflammatoires. Cela permet au cortex insulaire d'intégrer les informations extéroceptives et intéroceptives et de jouer un rôle central dans le ‘salient network'. Au sein de l'organisme, il peut optimiser les réponses à des situations spécifiques en régulant l'activité cardiaque ou intestinale, ainsi que les réponses immunitaires, mais les circuits qui médient ces fonctions ne sont pas bien connus. Compte tenu de l'importance du nerf vague dans la transmission d'informations entre le cerveau et la périphérie, ainsi que l'existence de projections du cortex insulaire vers le complexe vagal (InsCtxVC), nous émettons l'hypothèse que certaines fonctions du cortex insulaire sont médiées par le nerf vague. Pour étudier le rôle de l'InsCtxVC, nous avons d'abord caractérisé ces neurones anatomiquement à l'aide d'un virus rétrograde permettant leur marquage. Nous avons constaté que les neurones InsCtxVC sont principalement situés dans le cortex insulaire postérieur-intermédiaire dans la couche V, et expriment CTIP, un effecteur en aval de la voie Fezf2. Ensuite, nous avons examiné les entrées et sorties de ces neurones en utilisant des marqueurs viraux. Nos expériences ont révélé qu'au sein du complexe vagal, les neurones InsCtxVC établissent préférentiellement des synapses avec le NTS médian (plutôt que le NTS caudal ou le DMN), ainsi qu'avec l'amygdale centrale et le noyau parasubthalamique. De plus, nous avons analysé leurs entrées présynaptiques, mettant en évidence une innervation prédominante des cortex sensoriels, y compris le cortex insulaire lui-même, et les cortex somatosensoriels et olfactifs. Sur la base de nos résultats anatomiques et de la littérature, nous avons examiné divers contextes susceptibles de recruter l'InsCtxVC. Grace à des manipulations chemogénétiques et optogénétiques spécifiques de ces neurones, nous avons constaté que l'InsCtxVC n'est pas impliqué dans les comportements anxieux ou l'aversion gustative conditionnée neuro-immunitaire. Cependant, l'activation chemogénétique des neurones InsCtxVC lors d'une inflammation induite par le LPS exacerbe le comportement de maladie, incluant une perte de poids accrue, une élévation des cytokines pro-inflammatoires et de la corticostérone dans le sang.En conclusion, nos résultats caractérisent une population neuronale non décrite précédemment reliant le cortex insulaire à un centre parasympathique majeur régulant les réponses immunitaires périphériques
Brain-body interactions are crucial for organisms survival; the brain constantly receives external and internal information that it integrates to regulate various physiological function. Notably, the nervous system closely interacts with the immune system. In the case of inflammation, the brain's features enable an optimized regulation of immune responses. These features include the brain's ability to sense environmental cues, anticipate outcomes, and transmit signals rapidly through an extensive network of neurons innervating the entire body within milliseconds. The vagus nerve, linking the brain to visceral organs, is an important support of this bidirectional communication. It is composed of sensory and motor branches. Sensory afferences carry peripheral information to the vagal complex in the brain which transmits the signals to deeper brain structures, while motor efferences mediate the generated responses to targeted organs.In processing internal information, the insular cortex emerges as a critical multimodal hub. As a sensory cortex, it receives various inputs from external-sensing systems such as somatosensory, and olfactory cortices, while also being densely interconnected with regions processing internal cues such as inflammatory threats, such as the vagal complex. This allows the insular cortex to integrate exteroceptive and interoceptive information and play a pivotal role in the salience network. Within the organism, it can optimize responses to specific situations by regulating cardiac or intestinal activity, as well as immune responses, but the underlying circuits are poorly understood. Given the role played by the vagus nerve in transmitting information between the brain and the periphery, along with the presence of projections from the insular cortex to the vagal complex (InsCtxVC), we hypothesize that some of the insular cortex functions are mediated through the vagus nerve.To investigate the role of InsCtxVC, we first characterized these neurons anatomically using viral retrograde labeling. We found that InsCtxVC are predominantly located within the posterior-intermerdiate InsCtx, mainly in layer V, and express CTIP, a downstream effector of the Fezf2 pathway. Next, we examined the connectivity of these neurons using viral labeling of outputs and inputs. Our experiments revealed that within the vagal complex, InsCtxVC neurons preferentially synapse with the medial NTS (rather than caudal NTS or DMN), and the central amygdala and parasubthalamic nucleus. Additionally, we analyzed their presynaptic inputs, highlighting a predominant innervation from sensory cortices including the insula itself, the somatosensory and olfactory cortices. Based on our anatomical findings and existing litterature, we screened various contexts likely to recruit the InsCtxVC. Through specific chemogenetic and optogenetic manipulation of these neurons, we found that InsCtxVC are not involved in anxiety behaviors or neuroimmune conditionned taste aversion. However, chemogenetic activation of InsCtxVC neurons during early LPS-induced inflammation exacerbates sickness behavior, including increased weight loss, elevated blood proinflammatory cytokines and corticosterone response. Taken together, our results characterize a previsouly undefined neuronal population linking the insular cortex to a major parasympathetic center, which regulates immune responses in the periphery

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Dupont, Claire. "Séquelles anatomiques et fonctionnelles des maladies inflammatoires chroniques de l'intestin (MICI) de l'enfant." Thesis, Normandie, 2019. http://www.theses.fr/2019NORMR065.

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Les maladies inflammatoires chroniques de l’intestin (maladie de Crohn, rectocolite hémorragique, colite inclassée) de l’enfant peuvent occasionner des séquelles anatomiques telles que la fibrose intestinale responsable de sténoses, ainsi que! des troubles fonctionnels intestinaux (TFI) persistants lors de la rémission de la maladie. L’objectif de la thèse était d’estimer l’impact de ces complications et de rechercher une association avec les caractéristiques antérieures de la maladie. Nous avons utilisé pour cela deux séries pédiatriques et deux modèles animaux. Dans l’étude TFI\MICI, nous avons montré que 20% des enfants et adolescents avec MICI en rémission clinique et biologique avaient des TFI, et 15% des douleurs abdominales fonctionnelles (DAF). Les DAF étaient associées à une fatigue accrue, à des symptômes dépressifs et une diminution de la qualité de vie, mais pas à de l’anxiété. Il n’y avait pas d’association entre la gravité de la MICI et la présence de DAF. Dans l’étude STENO\PED, nous avons montré que les seuls critères cliniques et radiologiques associés à la nécessité de résection chirurgicale des enfants ayant une maladie de Crohn sténosante du grêle étaient une dilatation sus-sténotique > 30 mm et un PCDAI > 22,5 au diagnostic de sténose. L’administration d’un traitement anti-TNF après le diagnostic de sténose était un facteur protecteur par rapport au risque de chirurgie. Il manque de modèles expérimentaux permettant de suivre l’histoire naturelle de la fibrose intestinale en lien avec l’inflammation et l’effet des traitements, notamment chez l’animal pré-pubère. Nous avons adapté au rat pré-pubère un modèle de colite aiguë (1 dose de TNBS) et chronique (3 doses de TNBS) et avons montré que les rats développaient une inflammation significative dans les 2 modèles, basé sur un score histologique. L’IRM montrait un épaississement de la paroi colique et des sténoses dans les 2 modèles, et des ulcérations de la muqueuse dans le modèle aigu. En histologie, il y avait une fibrose légère à modérée dans le modèle TNBS chronique et une ébauche non significative de fibrose dans le modèle aigu. Le traitement des rats par MODULEN IBD® exclusif dès le début de l’induction de l’inflammation n’a pas entraîné de diminution de l’inflammation ni de la fibrose histologiques dans les deux modèles. La prise en charge des séquelles anatomiques et fonctionnelles des MICI pédiatriques devient un enjeu majeur même si la prévalence des douleurs fonctionnelles nous est apparue comme non augmentée par rapport à la population générale. Les modèles animaux pré-pubères pourraient permettre de mieux analyser la cinétique de la fibrogenèse et l’impact d’une suppression précoce de l’inflammation et/ou de nouvelles thérapeutiques anti-fibrosantes
The course of pediatric-onset inflammatory bowel disease (Crohn’s diseae, ulcerative colitis and IBDD unclassified) can be complicated by structural or functional sequelae. Structural complications include intestinal fibrosis which can cause bowel strictures. IBD can be associated with functional abdominal pain persisting despite remission of inflammation. The purpose of our work was to determine the burden of these complications and search for association with previous severity of inflammation, based on!two clinical studies and two animal models. In the first study, TFI-MICI, we showed that 20% of children and adolescents with IBD in clinical and biochemical Remission had functional gastrointestinal disorders, among which 15% had functional abdominal pain disorders (FAPD). FAPD was! Ssociated with increased fatigue, depressive symptoms and reduced quality of life, but not with anxiety. There was no association between the severity of IBD and presence of FAPD. The second study, STENO-PED, focused on imaging and clinical predictors of response!to treatment in children and adolescents with stricturing small bowel Crohn’s disease. We showed that the predictors for surgery were a dilation proximal to the stricture of >30mm, and a PCDAI score at diagnosis of stricture > 22.5. Receiving an anti-TNFα treatment after diagnosis of stricture was a protective factor from surgery. Experimental models allowing to follow the progression of fibrosis along with inflammation and assess response to Treatment are lacking, in particular for pre-pubertal animals. We adapted to Sprague-Dawley pre-pubertal rats a model of acute (1 dose of! TNBS) and chronic (3 doses of TNBS) hapten-induced colitis. The rats in both models developed significant inflammation, based on histology and magnetic resonance colonography. Rats in the chronic colitis model developed histologic fibrosis. There was a non-significant trend to fibrosis in the acute model. !We treated rats in both models with MODULEN IBD® from induction of colitis to collection of colonic samples. This treatment did not reverse inflammation nor fibrosis. Fibrosis and functional abdominal pain in pediatric-onset IBD are two important problems, although functional pain appeared to be not more frequent than in the general population. Animal models could be of great assistance in order to better decipher the link between inflammation and fibrosis, and see if an effective early suppression of inflammation along with new anti-fibrotic therapies could halt the progression of fibrosis

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Chen, Zheng-wang. "Isolation and characterization of novel intestinal polypeptides of the enteroinsular and brain-gut axes and of macrophages /." Stockholm, 1997. http://diss.kib.ki.se/1997/19971212chen.

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Gabriel, Tristan. "Rôle du système immunitaire intestinal au sein de l’axe microbiote-intestin-cerveau dans les symptômes psycho-comportementaux." Electronic Thesis or Diss., Saint-Etienne, 2023. http://www.theses.fr/2023STET0035.

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Les connaissances grandissantes sur l’association entre anomalies du microbiote et du système immunitaire chez les patients présentant des troubles psychiatriques, font de l’axe microbiote-intestin-cerveau un acteur indispensable à étudier. Les objectifs de ce travail de thèse consistent en l’étude du rôle du système immunitaire intestinal dans les troubles psycho-comportementaux. Le premier objectif de caractérisation du système immunitaire muqueux intestinal a été réalisé par une étude clinique dans une population de patientes souffrant d’anorexie. Une surprenante absence de marqueurs inflammatoires et une plus grande fréquence de lymphocytes T régulateurs circulants a été mise en évidence. Notre second objectif a consisté à étudier l’impact du microbiote sur le comportement. Il a été montré que le microbiote fécal de patientes présentant une anorexie mentale sévère entraine une inflammation chez les animaux et des anomalies sur les comportements anxieux lors de tests. Nous avons pu initier un projet de puce mettant en relation des cellules immunitaires et des neurones pour étudier la transduction de signaux inflammatoire, constituant la première preuve de concept de modélisation de la voie nerveuse in vitro de l’axe microbiote-intestin-cerveau. Notre troisième objectif consista à caractériser les atteintes psycho-comportementales dans les phénomènes immuno-pathologiques des maladies inflammatoires chroniques de l’intestin. L’identification d’une très forte prévalence du symptôme aboulie chez des patients faisant l’expérience d’une fatigue persistante malgré une maladie intestinale quiescente, fait évoquer des anomalies des structures cérébrales impliquées dans les domaines des valences positives (motivation). Ces éléments ont fait l’objet d’une étude sur le modèle animal de colite inflammatoire induite au DSS, dont l’étude comportementale doit encore être améliorée. L’ensemble de ces éléments alimente l’hypothèse d’une forte implication du microbiote et du système immunitaire intestinal comme unité pouvant modifier pathologiquement le fonctionnement cérébral, et se traduire de manière psycho-comportementale chez les sujets. L’axe microbiote-intestin-cerveau part sa richesse, concentre les espoirs d’une révolution en psychiatrie tant pour le diagnostic, le pronostic, que la thérapeutique
Growing knowledge of the association between microbiota and immune system abnormalities in patients with psychiatric disorders makes the microbiota-gut-brain axis an indispensable player to study. This thesis aims to explore the role of the intestinal immune system in psychobehavioral diseases. The first objective of characterizing the intestinal mucosal immune system was achieved through a clinical study of female patients suffering from anorexia. A surprising absence of inflammatory markers and a higher frequency of circulating regulatory T lymphocytes were demonstrated. Our second objective was to study the impact of microbiota on behavior. The fecal microbiota of patients with severe anorexia nervosa has been shown to cause inflammation in animals and abnormalities in test anxiety behavior. We initiated a microarray project linking immune cells and neurons to study inflammatory signal transduction, constituting the first proof-of-concept for modeling the in vitro neural pathway of the microbiota-gut-brain axis. Our third objective was to characterize the psycho behavioral effects of immuno-pathological phenomena in chronic inflammatory bowel disease. They identify a very high prevalence of the symptom abulia in patients experiencing persistent fatigue. However, quiescent bowel disease indicates abnormalities in brain structures involved in positive valence (motivation) domains. These elements have been studied in an animal model of inflammatory colitis induced by DSS, whose behavioral study still needs to be improved. These elements support the hypothesis that the microbiota and the intestinal immune system are strongly implicated as a unit capable of pathologically modifying cerebral functioning and translating into psycho-behavioral effects in subjects. The richness of the microbiota-gut-brain axis raises hopes of a revolution in psychiatry regarding diagnosis, prognosis, and treatment

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De, Vadder Filipe. "Détection portale des nutriments et contrôle de l'homéostasie énergétique par l'axe nerveux intestin-cerveau." Phd thesis, Université Claude Bernard - Lyon I, 2014. http://tel.archives-ouvertes.fr/tel-01058661.

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La production endogène de glucose est une fonction cruciale de l'organisme, permettant de maintenir l'homéostasie glycémique. Alors que la production accrue de glucose par le foie a des effets délétères, la néoglucogenèse intestinale (NGI) exerce des effets bénéfiques sur l'équilibre métabolique de l'organisme. Les régimes hyperprotéiques sont connus pour leurs effets de satiété. Grâce à des travaux physiologiques et moléculaires chez le rat et la souris, nous montrons dans une première partie que l'effet bénéfique des régimes hyperprotéiques passe par une induction de la NGI. Lors de la digestion des protéines alimentaires, des di- et tripeptides sont libérés dans la veine porte. Ces molécules agissent comme des antagonistes des récepteurs μ-opioïdes de la veine porte, initiant un arc réflexe intestin-cerveau induisant la NGI et la satiété. Dans un deuxième temps, nous proposons un modèle rendant compte des effets bénéfiques des régimes riches en fibres, tels que l'amélioration de la sensibilité à l'insuline et l'induction de la dépense énergétique. Les fibres solubles sont fermentées par le microbiote intestinal, produisant des acides gras à chaîne courte (AGCC), acétate, propionate et butyrate, à l'origine des effets métaboliques observés. Nous montrons que le butyrate active directement les gènes de la NGI dans les entérocytes, et que le propionate se lie aux récepteurs FFAR3 dans le système nerveux périportal, initiant un mécanisme de communication entre l'intestin et le cerveau induisant la NGI. De plus, nous montrons que la modification de la composition du microbiote par les fibres alimentaires n'est pas suffisante en soi pour induire les effets bénéfiques en absence de NGI

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Voinot, Florian. "Axe cerveau-intestin et contrôle de la prise alimentaire : exemple d'altérations chez un modèle animal de schizophrénie." Phd thesis, Université de Strasbourg, 2012. http://tel.archives-ouvertes.fr/tel-00790379.

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L'axe cerveau-intestin désigne l'interaction bidirectionnelle entre le cerveau et le tube digestif. Bien que la leptine, hormone produite par le tissu adipeux, participe à la régulation de cet axe, son mode d'action dans le système nerveux entérique a été peu étudié. A l'heure actuelle, une relation étroite entre une perturbation de l'axe cerveau-intestin et la schizophrénie est supposée. Par conséquent, les objectifs de ce travail étaient d'évaluer 1) les effets ex vivo de la leptine dans la neurotransmission entérique chez le rat et 2) les altérations périphériques dans un modèle neurodéveloppemental de la schizophrénie (NVHL) chez le rat. Nous avons montré que la leptine module l'activité des neurones entériques inhibiteurs et excitateurs dans le jéjunum et le côlon proximal. L'implication des neurones afférents primaires intrinsèques a été discutée. Chez les rats NVHL, nous avons mis en évidence une réduction de la masse corporelle, des variations hormonales, une inflammation du jéjunum et des altérations motrices digestives. La relation entre les troubles périphériques, notamment vagaux, et la physiopathologie de la schizophrénie a été discutée.

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Angelides, Sophia Morfea. "The gut-brain axis and cognition." Thesis, 2018. https://hdl.handle.net/2144/32981.

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The gut and the brain are in constant communication through pathways that include the immune system, the nervous system, neurotransmitters, and hormones. Modifications in the gut, especially the gut microbiome, have the potential to cause changes in the brain resulting in behavioral and cognitive changes. A healthy and diverse microbiome, which may be achieved by a high fiber diet or probiotic or prebiotic treatments, is associated with improvements in cognition. Gut dysbiosis and a decrease in diversity of the microbiota, which may be caused by a western diet or antibiotic treatments, is associated with cognitive decline and decreased memory. There are many possible pathways through which these changes in the gut act to change cognition, including the immune system, the expression of brain derived neurotropic factor, metabolites such as short chain fatty acids, gut hormones, and neurotransmitters. If researchers can decipher which pathways are involved in modifying cognition, they may be able to identify treatments that can help improve memory and specifically decrease age-related cognitive decline.

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KOCZWARA, JUSTYNA BARBARA. "Oleoylethanolamide in the gut-brain axis." Doctoral thesis, 2019. http://hdl.handle.net/11573/1307548.

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Oleoylethanolamide (OEA), a PPAR-α agonist, is a mediator of satiety. After peripheral administration, OEA induces Fos expression and activation in areas of the CNS involved in the control of feeding behavior and energy homeostasis, such as the nucleus of the solitary tract (NST) and in the area postrema (AP) in the brainstem, the hypothalamic paraventricular (PVN), supraoptic (SON) and ventral tuberomammillary (vTMN) nuclei. Moreover, it is known to increase the noradrenergic trasmission in the NST and AP, by increasing the expression of the dopamine-β-hydroxylase (DBH). Visceral ascending fibers were hypothesized to mediate such effects, but recent findings demonstrate that abdominal vagal afferents are not necessary for the anorectic effect of OEA. In fact, OEA is able to decrease food intake both in rats that underwent a subdiaphragmatic vagal deafferentation (SDA), a surgical procedure that eliminates all abdominal vagal afferents but spares about 50% of the vagal efferents, and in SHAM controls. Thus, the aim of the present work was to better elucidate the role of abdominal vagal afferents in mediating OEA's effects on the CNS. To meet this aim, we subjected rats to SDA surgery, using SHAM rats as control. By using immunohistochemistry, Fos and DBH expression patterns were investigated in the NST, in the AP, and in the hypothalamus after OEA administration (10 mg kg -1). Consistently with the behavioral results, OEA increases Fos expression in the NST and in the AP. Moreover, in these nuclei, SDA did not cause any alteration of DBH expression. In the hypothalamus, in line with the behavioral results, OEA is able to increase Fos expression in the PVN and the vTMN, even though in the latter does not reach statistical significance. Overall, our findings indicate that vagal afferents are not strictly necessary for the satiety effect of OEA at both behavioral and neurochemical levels.

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Barros, João Tomás da Silva. "Changes in the Gut-Brain axis during aging." Master's thesis, 2020. http://hdl.handle.net/10316/93972.

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Dissertação de Mestrado em Biologia Celular e Molecular apresentada à Faculdade de Ciências e Tecnologia
Atualmente, pensa-se que inflamação sub-crónica e um microbioma intestinal alterado poderão estar subjacentes à patogénese de doenças neurodegenerativas, tais como na doença de Parkinson. O descrito aumento do número de citocinas pró-inflamatórias tanto no sangue, como em biópsias colónicas de doentes de Parkinson permitiu conectar, assim, imunidade gastrointestinal com inflamação. Uma vez que os pacientes desta doença muitas vezes apresentam disfunção intestinal acrescenta peso à importância da interação intestino-cérebro no desenvolvimento da neurodegeneração. Uma vez que perturbações gastrointestinais podem ocorrer até décadas antes do aparecimento de sintomas motores, mudanças no microbioma intestinal poderão ser identificadas como prognóstico antecipado. Assim, a disrupção entre bactérias comensais e patogénicas no intestino, tal como acontece com o envelhecimento, poderá aumentar a suscetibilidade à doença de Parkinson.Este estudo teve como objetivo verificar que as alterações que ocorrem no microbioma com o envelhecimento, deixam ratinhos mais suscetíveis ao desenvolvimento da doença de Parkinson. Mais, ponderamos que a acumulação de ferro no intestino durante o envelhecimento fosse a causa deste desequilíbrio, um processo que poderia ser reversível com terapia de quelantes de ferro, revertendo assim a inflamação intestinal. Este estudo procurou ainda descobrir se uma redução de ferro no intestino seria suficiente para reduzir a neuroinflamação mediada pelas interações intestino-cérebro, e, como tal, a severidade da doença de Parkinson em ratinhos.Ratinhos C57BL/6 foram usados como modelo pré-clínico de modo a alcançar os objetivos deste estudo. Comparações entre ratinhos relativamente novos (8-12 semanas) e velhos (52-60 semanas) foram realizadas de forma a analisar a inflamação intestinal e a acumulação de ferro, com ou sem a administração de terapias quelantes. As interações intestino-cérebro foram avaliadas associando os resultados obtidos no intestino com um aumento na neuroinflamação e acumulação de ferro no cérebro. Um modelo farmacológico da doença de Parkinson foi induzido através da administração de 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), uma neurotoxina exclusiva dos neurónios dopaminérgicos da substantia nigra cérebro. Transplantes fecais também foram efetuados para avaliar se a alteração do microbioma intestinal influencia o perfil neuro inflamatório de ratos velhos e, consequentemente, a severidade da doença.Dados preliminares a suportar a hipótese colocada já foram adquiridos pelo mesmo laboratorio, tendo sido crucial a sua validação com o plano experimental proposto. Esta tese almejou conseguir provar que as mudanças no microbioma com o envelhecimento são capazes de influenciar o fenótipo neuro-inflamatório de ratinhos velhos, aumentando a sua suscetibilidade à doença. Esperou-se também mostrar que os mecanismos moleculares subjacentes a este fenómeno, necessitavam de acumulação de ferro no intestino, um processo que aumenta a patogenicidade bacteriana e modula a resposta imune.
Low-grade chronic inflammation and altered composition of gut microbiota have been suggested to underlie the pathogenesis of neurodegenerative diseases, such as Parkinson’s disease (PD). An increased level of pro-inflammatory cytokines was found in both peripheral blood and colonic biopsies of PD patients, an observation that allowed linking gut immunity and inflammation. The notion that PD patients usually present intestinal dysfunction and constipation further strengthens the importance of a gut-brain interaction during the development of neurodegenerative diseases, like PD. Since gastro-intestinal (GI) manifestations often occur a decade before the appearance of severe motor deficits, changes in gut microbes can be identified as early PD symptoms. Hence, the disruption between commensal and pathogenic bacteria in the gut, as physiologically occurs during aging, is thought to favor an increased susceptibility to PD.This study aimed to verify that changes occurring in the gut microbiota during aging rendered mice more susceptible to PD. Moreover, we hypothesized that the accumulation of iron in the gut during aging was the underlying cause of this unbalance, a process that could be reversed with the administration of iron chelators that prevent these changes to trigger gut inflammation. This study was also able to assess whether a reduction of iron in the gut was capable to reduce the gut-brain axis-induced neuroinflammation and, as such, the severity of PD, in mice.C57BL/6 mice were used, as a pre-clinical animal model, to address the objectives of this study. Comparisons between relatively young (8-12-weeks old) and old (52-60-weeks old) mice was carried out, in terms of gut inflammation and iron accumulation, with or without the administration of iron chelation therapy. The gut-brain axis was evaluated by associating the results obtained in the gut with an increased neuroinflammation and iron accumulation in the brain. A pharmacological model of PD was induced by the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin known to target exclusively dopaminergic neurons in the substantia nigra of the brain. Fecal transplantation was also used to address whether changing the composition of the gut microbiota could influence the neuro-inflammatory profile of aged mice and, subsequently, the severity of PD.Preliminary data supporting the hypotheses put forth were already obtained in the laboratory, so it was crucial their validation with the experimental plan proposed to complete my studies. This research was expected to prove that changes in gut microbiota occurring during aging were capable to influence the neuro-inflammatory phenotype of older mice and to increase the severity of PD. Furthermore, it was also expected to show that the molecular mechanism underlying this phenomenon relied on the accumulation of iron in the gut, a process known to increase bacteria pathogenicity and to modulate the inflammatory response. Lastly this study also addressed the salutary effect of iron chelation therapy in PD, providing proof of concept that its beneficial effects were also due to its ability to diminish gut inflammation.
Outro - Investigator Programme (IF/01495/2015). Financiamento concedido pela Fundação pela Ciência e Tecnologia (FCT) para o projeto de investigação científica titulado: “Immunity and inflammation in Parkinson’s disease”.

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Borrelli, Luca. "THE MICROBIOTA-GUT-BRAIN AXIS. A STUDY IN ZEBRAFISH (DANIO RERIO)." Tesi di dottorato, 2015. http://www.fedoa.unina.it/10221/1/Borrell_Luca.pdf.

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The microbiota is essential in the host's physiology, development, reproduction, immune system, nutrient metabolism, in brain chemistry and behavior. The gut microbiota plays a crucial role in the bidirectional gut–brain axis, a communication that integrates the gut and central nervous system (CNS) activities, and thus, the concept of microbiota–gut–brain axis is emerging where the microbes have considered as signaling components in the gut-brain axis. Animal studies reveals, in particular, that gut bacteria influence the brain-derived neurotrophic factor (BDNF) levels, and behavior specially after probiotic administration. How this alterations in brain chemistry are related to specific behavioral changes is unclear but it will likely be a focus of future research efforts. Among these animal studies, to our knowledge, no studies on the microbiota–gut–brain axis in zebrafish (Danio rerio) have been carried out. We hypothesized that a continuous administration of an exogenous probiotic might also influence the host's behavior and neurochemical gene expression. The purpose of this study was to determine whether probiotic strain can modulate gut commensal bacteria influencing brain neurochemistry and behavior in zebrafish. Thus, we treated adult zebrafish for 28 days with Lactobacillus rhamnosus, a probiotic strain which is one of the main components of the commensal microflora of human intestinal tract and it is widely used as a probiotic in mammals to adult male and female AB wild tipe zebrafish. We established differences between treated with probiotic strain and control group in shoaling behavior pattern, using a Video Tracker software; we quantified brain-derived neurotrophic factor (BDNF) gene expression by using RT-qPCR; we at last analyzed the microbiota profiles within two experimental groups by sing the culture-independent methods such as Denaturing Gradient Gel Electrophoresis (DGGE) and Next-Generation Sequencing (NGS). The probiotic treated group, compared to the control group, showed a statistically significant near two-fold increase in BDNF gene expression, different shoaling behavioural pattern and a shift in microbiota composition with a significant increase of Firmicutes and a reduction of Proteobacteria. The results of each approach may support the existence of a microbiota–gut–brain axis, in adult zebrafish and in line with numerous animal studies we can speculate that microbiota manipulation could influence behavior and brain expression of BDNF.

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Ficara, Austin Charles. "Influence of the human gut microbiota on depression and anxiety." Thesis, 2019. https://hdl.handle.net/2144/38603.

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Depression and anxiety disorders affect upwards of one in six individuals at some point in their life making them the most prevalent mental illnesses today. Recent evidence has suggested a possible correlation between the human gut microbiota and the development of depressive and anxiety-like symptoms through a signaling pathway termed the microbiota-gut-brain axis. In both animals and individuals suffering from depression and anxiety-like symptoms, alterations in their gut microbial composition seem to compromise the function of this pathway. In addition to this microbiota-gut-brain axis, other microbiota-derived molecules have been linked to symptoms of depression and anxiety. Given this emerging role of the gut microbiome and gut–brain axis, it is crucial to understand the factors shaping our gut microbiome in order to determine potential therapeutic strategies to treat depression and anxiety. Following a concise review of the human microbiome, depression/anxiety, and the gut-brain axis, I will examine the gut microbiota role as a regulator of depression and anxiety. In addition, other biological markers associated with both the gut microbiome and these disorders will be reviewed. Lastly, I will evaluate the gut microbiome as a prospective therapeutic target for mental illnesses such as depression and anxiety.

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Mennella, Ilario. "STUDY OF DIETARY FACTORS FOR BODY WEIGHT CONTROL THROUGH GUT BRAIN-AXIS." Tesi di dottorato, 2016. http://www.fedoa.unina.it/11018/1/Mennella%20Ilario%20-%2027.pdf.

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The physiological systems underlying the appetite control involve associations between peripheral physiology and metabolism (glucose homeostasis and adiposity), which in turn are linked to various brain processes. All hormonal messengers released from enteroendocrine cells in the gut mucosa can inform the brain either through the circulation or via primary afferent neurons or both. Gut hormones and adipokines interact each other in the control of body weight. In particular, visceral fat accumulation causes chronic low-grade inflammation, which contributes to the initiation and progression of metabolic disorders. Chronic low-grade inflammation, caused by the constant higher release of pro-inflammatory adipokines from adipose tissue, disrupt the gut hormones signalling at central and peripheral leves in the control of appetite and body weight. In this scenario the experiments described in the present thesis investigated mechanisms involved in both gut and brain regulation of food intake. In the experiments described in the chapthers 2 and 3 we tested in animals and in humans the hypothesis that dietary whole grains (WG) fibers are able to control body weight through a mechanism involving appetite control and the reduction of infiammatory status. In charter 4 we described a method to mimic the WG slow release of antioxidant compounds using encapsulation. Finally, in charter 5 we tested the hypothesis that the fat taste can influence the cephalic phase of the digestion. From the studies described in the present thesis, it can be concluded that: 1. The consumption of WG in substitution of refined cereals reduce subclinical inflammation and this effect is strengthen when WG are combined with prebiotic fibre. In fact, together the consumption of WG resistant starch is able to modulate two main components of the GBA, helping to restabilising an healthier physiological condition: cytokines and gut-microbiota. This effect is mediated by the slow release of bound phenolic compounds which are released from the fibre matrix during the gut microbiota fermentation. Therefore, the addition of a prebiotic fibre able to stimulate the growth and the activity of the gut microbiota increase the release of phenols from WG cereals. 2. Novel ingredients can be designed using encapsulation to obtain a slow release of antioxidant compounds and increase their bioavailability. In fact, a key lesson from the study of phenolic compounds from WG is that the kinetic of their absorption follows a slow but constant pattern: this guarantee a stable antioxidant protection in the bloodstream. In the present thesis, we used curcuminoids as a natural antioxidant -ingredient well-know for their healthy properties and low-grade bioavailability. The same approach can be used for many others antioxidant compounds. 3. Food consumption can modulate the endocannabinoids system which in turn influence eating behaviour. During the cephalic phase of the digestion, when food is chewed and even before swallowing, a variation of the ECs in saliva and plasma already appear. This evidence suggest a main role of cephalic phase in the digestive processes related to meal initiation and meal termination.

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Rashid, Naureen. "Irritable bowel syndrome: analyzing the brain-gut axis and efficacy of psychological treatment." Thesis, 2017. https://hdl.handle.net/2144/23848.

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Irritable bowel syndrome (IBS) is the most common chronic functional gastrointestinal disorder that affects approximately 11% of the global population with a higher prevalence in women and those under the age of 50. IBS is characterized and diagnosed by the presence of a group of symptoms including abdominal pain, bloating or distension accompanied by altered bowel movements. A positive diagnosis of IBS can be made in the presence of well-defined, validated diagnostic criteria and in addition to the exclusion of organic disease with minimal testing. The lack of specific therapeutic targets makes treatment of IBS very difficult and its management is focused on symptom relief. IBS has a well-established high comorbidity with anxiety, depression, and psychosomatic disorders which contributes significantly to a substantial burden of illness. IBS patients exhibit a markedly decreased quality of life, decreased work productivity and increased absenteeism from work, and increased direct healthcare utilization (such as office visits, medical tests, and specialty referrals), resulting in a large economic burden for society. Despite this, effective pharmacologic and non-pharmacologic treatment options are limited and many patients with IBS do not achieve complete symptom relief long term and continue to suffer from IBS symptoms. Early pioneering in the study of this disease has called for a biopsychosocial model, a model in which psychological and social factors are also considered in IBS treatment. Through consideration of this model, it has been discovered that the disease has strong ties with early life environment, daily stress, and coping skills. Research in the past decades has established IBS as a disease of neurogastroenterology and involves disturbances in the brain-gut axis, the connection between the central nervous system and enteric nervous system. The brain-gut axis is organized in hierarchies with the first control level consisting of the enteric nervous system (ENS) sensory, muscular, and interneurons, all of which form reflex circuitry to control gastrointestinal (GI) motility and sensation among other functions. The central nervous system (CNS) synapses onto these circuits via vagal and spinal afferents. Information from the luminal GI tract is processed in the higher cortical structures of the brain, particularly in the hypothalamus, amygdala, anterior cingulage cortex (ACC) and prefrontal cortex (PFC). These structures are also important for homeostasis and regulation of attention, emotion, and behavior. Disturbances of these pathways result in peripheral and eventually central sensitization, the subject of this thesis. Sensitization in IBS includes visceral hypersensitivity, increased pain perception, and increased GI motility. Due to the cortical regions where this information is processed, these physical symptoms often have a complex interplay with psychological symptoms including anxiety, fear, and stress. The connection between the physical symptoms and psychological symptoms lies in the pain matrix and emotional motor system. This has been confirmed by many brain imaging studies comparing normal individuals with IBS patients testing visceral, somatic and cutaneous pain as well as anxiety and depression levels. IBS patients, unlike control subjects, have been found to have increased pain perception localizing to all these regions and they also rate the pain as more unpleasant, a psychological factor, than normal patients. In addition to increased cortical activation, IBS patients have increased corticotropin releasing factor in the amygdala promoting anxiety and increasing stress levels and GI symptoms. Of note is the fact that stress is both a cause and effect of IBS symptoms and often compounds symptoms due to the cyclical nature of stress and chronic pain. Because stress ties in with both the physical and psychological symptoms faced by IBS patients, implementation of psychological treatment in IBS management is of great importance and have demonstrated improved outcomes in IBS patients. Psychological treatments with empirical evidence are discussed in this thesis and include cognitive behavioral therapy, psychodynamic psychotherapy, hypnotherapy, and mindfulness/relaxation exercises. Whether these all treatments tie into the alterations in cortical processing in brain-gut function is a topic that is yet to be explored.

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Groot, Michael. "Evaluating the gut-brain axis of Parkinson's disease pathogenesis and exploring potential therapies." Thesis, 2019. https://hdl.handle.net/2144/36523.

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Parkinson’s Disease is a neurodegenerative illness of the central nervous system that impacts both cognitive and motor functioning. Current understanding dictates that these symptoms are caused by the death of dopaminergic neurons within the substantia nigra pars compacta of the basal ganglia. This neuronal death explains part of the symptoms, but large clumps of insoluble protein called Lewy Bodies are thought to also contribute. The α-synuclein (α-SN) protein is a major component of Lewy Bodies and has long been demonstrated to misfold and become aggregated. Classically, these Lewy Bodies first appear within the brainstem and spread upwards towards the cortex as the pathology progresses. While there have been some suggestions, the mechanism whereby α-SN misfolds in the brainstem is not currently understood. Additionally, the interplay between Lewy Bodies and dopaminergic neuronal death has not yet been discovered. One of the leading theories of α-SN misfolding is related to the gut-brain axis. Our gastrointestinal tract is innervated by the enteric nervous system, which sends signals to the brainstem via the vagus nerve. Curiously, α-SN is expressed within enteroendocrine cells of the intestine. These cells have connections to nerve fibers of the enteric nervous system at their basal lamina. The hypothesis reasons that some pathogenic agent can gain access to the cells of the intestine, cause α-SN to misfold, and cause this damaged protein to be transported within the vagus nerve. As the vagus nerve ultimately connects to the brainstem, this is where the Lewy Bodies are deposited to initiate Parkinson’s disease. Research has investigated this connection thoroughly but has yet to determine definitively if this gut-brain axis is truly causing pathology within the brainstem. This thesis attempts to provide an overview of the current literature relating to Parkinson’s disease as well as the current knowledge of the gut-brain axis. Then, this will evaluate the various entities proposed to be the unknown pathogen of the gut-brain axis and discuss some of the controversies in the literature. Finally, this thesis will discuss the therapies that have arisen from the concept of the gut-brain axis and the potential further directions that these therapies imply for research.

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Lama, Adriano. "Pharmacological and nutritional control of dysbiosis related to CNS disorders: gut-brain axis." Tesi di dottorato, 2018. http://www.fedoa.unina.it/12578/1/lama_adriano_31.pdf.

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'Leaky gut' syndrome has attracted much attention in recent years, and represents now a complementary/alternative target for several complex diseases characterized by this pathological condition. It is often described as an increase in the permeability of the intestinal mucosa, allowing bacteria, toxic digestive metabolites, bacterial toxins, and small detrimental molecules to 'leak' into the bloodstream. The microbiota-gut is an integral component of the gut–brain neuroendocrine metabolic axis and any microbiota-gut disruption that can occur, could distressed homeostasis and share an inflammatory response, affecting distal organs including the brain. It has been shown, indeed, that the gut can influence the blood brain barrier (BBB) through gastrointestinal-derived hormones, small molecule and metabolic co-factor production, or through cytokine synthesis and other inflammatory mechanisms. Therefore, the CNS is under constant attack or, conversely, advantage from a wide variety of neuro-psychotropic-modulating microbes, and their metabolites. So, the proper neurodevelopment and functioning of the CNS depends from an integrated, rather than opposing, cross-talk between gut-gut microbiota and brain. Several CNS disturbances were related to gastrointestinal dysfunction and 'leaky brain', underlining the need of identifying new integrative and multi-targeted approaches. These complex diseases, being multifactorial, could result, in fact, less responsive to targeted standard drugs, since poorly fits ‘one-disease one-target’ and ‘one-target one-compound’ paradigms in this context. Here, we focused on autism spectrum disorders (ASDs) and major depressive disorder (MDD), two brain disorders linked to a dysfunction of BBB and impacted by immune and inflammatory peripheral stimuli. Our aim has been to evaluate the possible therapeutic potential of modulating several aspects of these multifactorial disorders, in order to benefit of peripheral and central contributions, converging on an improvement of overall health. To this aim we used BTBR T+tf/J (BTBR) mice model of ASDs and high fat diet-induced MDD in young mice, and the possible pharmacological modulation by palmitoylethanolamide (PEA) was investigated. PEA, is an endogenous N-acyl-ethanolamine, biosynthesized to maintain cellular homeostasis when this is challenged by external stressors provoking inflammation, neuronal damage and pain. The interaction and activation of PPARα has been recognized as the main mechanism of the effects evoked by this acylethanolamide. In particular, the analgesic and anti-inflammatory effects of PEA were demonstrated to be mediated by PPARα activation, since it has no effect in PPARα null mice. Indeed, the discovery of PPARα in distinct areas of the brain, opened a new scenario to explore the possible activity of this acylethanolamide in the CNS. Recently it has been demonstrated that genetic inactivation of PPARα, particularly abundant in the CNS, leads to a behavioral and cognitive phenotype reminiscent of that of preclinical models of ASDs, i.e. mouse model BTBR T+tf/J (BTBR), which displays an improved repetitive behavior when autistic mice are treated with a synthetic PPARα agonist. These results, not only indicated a central role for this receptor in neurological functions associated with the behavior, but more interestingly highlighted PPARα as a potential pharmacological target to lessen ASDs symptoms. On the other side PEA activity at intestinal level has suggested a possible role of this acylethanolamide in modulating not only gut function, such as intestinal transit and permeability, but also gut-brain axis. Before evaluating the effect of PEA on BTBR mice, in the first part of this PhD programme, we performed a study, also evaluating sex influence, on gut microbiota composition, behavioral features, and intestinal integrity, inflammatory status and architecture of adult male and female BTBR mice. These gender characterizations arise from the well-known different clinical features of male and female autistic patients and the need to identify them in a mouse model of ASD. Consistently with gut-brain axis hypothesis, we showed that BTBR mice presented a profound intestinal dysbiosis compared to control strain, more marked in female than in male mice, indicating Bacteroides, Parabacteroides, Sutterella, Dehalobacterium and Oscillospira genera as key drivers of sex-specific gut microbiota profiles associated with altered behavior. Interestingly, we also showed that the dysbiosis was accompanied in BTBR mice by increased gut permeability and colon inflammation. Therefore, we have considered BTBR mice, as an idiopathic model of autism useful to investigate not only the correction of the autistic behavior, but also a starting point to investigate whether the reduction of intestinal inflammation and integrity, and possibly the restoration of gut microbiota balance may ameliorate pathological traits. Based on this background, the aim of this study was to investigate the pharmacological effects of PEA on autistic-like behaviour of BTBR T+tf/J mice and to shed light on the contributing mechanisms. PEA was able to revert the altered behavior of autistic mice. This effect was contingent to PPARα activation, since was blunted by PPARα blocking or deletion. At mechanistic level, PEA restored hippocampal BDNF signaling, improved mitochondrial dysfunction and reduced serum, hippocampal and colonic inflammation. These beneficial effects were related to the reduction of leaky gut in PEA-treated BTBR mice mediated by increased expression of colonic tight junctions. In addition, PEA modulated gut microbiota composition, underlining the strong link between gut and brain. In last years, the connection between modification in gut microbiota induced by obesity and the development of MDD has become more evident. High fat feeding causes the production of several inflammatory mediators that can compromise colonic epithelial barrier function, with the translocation of bacterial metabolites in CNS, evoking deleterious events. The modulation of PPARα, mostly expressed in hippocampus, has demonstrated to improve synaptic dysfunction and HFD-related pathological events in MDD. Here, we have addressed the effects of PEA in a mouse model of HFD-induced depression, focusing on converging mechanisms involved in its activity. In particular, we assessed PEA capability in modulating the gut-brain axis and ameliorating depressive behavior. The treatment with PEA improved the depressive-like behavior and memory deficit, shown by HFD animals, impacting on BDNF signaling pathway and reducing neuroinflammation, both in hypothalamus, hippocampus and prefrontal cortex. These beneficial effects of PEA, as PPARα agonist, were correlated to an increased expression of PPARα, its coactivator PGC1α, and the downstream gene FGF21. As in BTBR model, here PEA also modulated gut microbiota composition, reducing the amount of endotoxin-producer Desulfovibrio and increasing Clostridiales genus relative abundance, and consistently Clostridiales-producing metabolites, including short-chain fatty acids. In conclusion, PEA, a multifunctional compound, can represent a novel therapeutic approach for multifactorial disorders, such as ASDs and MDD, able to counteract the alteration of central and peripheral pathways involved in their onset and progression.

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Kosenkova, Inna. "Possible impact of the gut microbiota on the excitability of the brain." Doctoral thesis, 2018. http://hdl.handle.net/11562/978978.

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It is becoming increasingly evident that the role of the gut microbiota (GM) is not limited by the walls of the gastrointestinal tract (supporting the digestion, absorption of nutrients, intestinal motility and resistance to pathogens), but it also influences normal physiology of the whole organism and contribute to the broad range of diseases including those affecting the central nervous system (CNS). The growing appreciation of the role of intestinal bacteria in brain physiology has led to the establishment of so called “gut-brain axis”, or the “microbiota-gut-brain axis”, a bidirectional communication network between the gut and the brain. We hypothesized that gut microbiota form subjects affected by neural pathology can modulate in healthy subjects excitability in CNS and, finally, positively correlate with the level of seizure activity. The data obtained in this study suggests that mice received “pro-pathological” microbiota have compromised brain excitability. Microbiota composition of the donors with induced temporal lobe epilepsy (TLE) was characterized by the increase in Sutterella, Prevotella, Dorea, Coprobacillus and Candidatus Arthromitus in comparison with the baseline. These alterations, through the GBA, may possibly have an effect on the excitability of the brain and subsequently on the threshold for the seizure activity.

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Huang, Sheng-Fu, and 黃聖富. "The combined effects of probiotics and nutritional supplement containing fish oil on gut immune response and gut-brain axis." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/38370799085739248927.

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碩士
國立臺灣大學
生化科技學系
102
Day and night, gut immune system encounters numerous foreign antigens. As a primary site of immune response initiation, it is important for gut immune system to distinguish from self and non-self antigen and affect subsequent immune response properly. The target product of this research includes two popular dietary factor: probiotics and DHA. It has been shown that both of them have certain immunomodulatory and anti-inflammatory effects. Here we give the treatment of probiotics and nutritional supplement containing DHA, separately or combined, to clarify their effect on gut immune system. In addition, we will measure the serotonin content in both intestine and brain to elucidate the link between probiotics or DHA, serotonin and gut-brain axis preliminarily. In non-specific immune animal model, 6 week-old female BALB/c mice were divided into several groups randomly: Ctrl, Probio, Suppl, (P+S)-0.5x, (P+S)-1 xand (P+S)-5x. Animal were sacrificed after 6-week treatment. In OVA-specific immune model, 6 week-old female BALB/c mice were divided into groups as previous. The treat dosage of (P+S)-5 xgroup was adjusted to (P-S)-2x, which received 2X dosage. Mice were immunized by OVA Intraperitoneal injection and sacrificed after 9-week sample treatment. After sacrifice, we analyzed the cytokine production of Peyer’s Patch (PP) and mesenteric lymph node (MLN) primary cell culture and the immunomodulatory cell populations in PP, MLN and splenocyte (SPL). we additionally measured the serotonin content in the tissue homogenate of intestine and brain via ELISA. Although the percentages of regulatory cell population were not affected, combined or separate sample treatment of probiotics and nutrition supplement containing DHA can increase regulatory cytokine production, including IL-10 and TGFβ. This data implies that the product has certain immunoregulatory function. On the other hand, probiotics and nutrition supplement containing DHA also made some impacts on the serotonin content in intestine and brain. However, the precise effects and mechanisms of these two dietary components on gut-brain axis need further elucidations.

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Zünd, Daniela. "Amylin als wichtige Komponente der "Gut-Brain-Axis" : immunhistochemische Untersuchungen am Gehirn der Ratte /." 2004. http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&doc_number=013152891&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA.

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Roque, Ana Filipa Silva. "Internship Reports and Monograph entitled "The Influence of Gut Microbiota in the Development of Schizophrenia"." Master's thesis, 2020. http://hdl.handle.net/10316/93120.

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Relatório de Estágio do Mestrado Integrado em Ciências Farmacêuticas apresentado à Faculdade de Farmácia
O microbiota intestinal humano é constituído por um vasto número de microrganismos,maioritariamente bactérias, que se co-desenvolveram com o seu hospedeiro humano.Recentemente, neurocientistas começaram a apreciar a influência da interação dinâmica entreos micróbios intestinais e os sistemas gastrointestinal e nervoso do seu hospedeiro,atualmente conhecido por eixo microbiota-intestino-cérebro. Esta comunicação bidirecionalenvolve vias imunológicas, neuronais, endócrinas e metabólicas. Evidências de estudosrealizados nos últimos anos sugerem que o microbiota pode estar associado a doençasneuropsiquiátricas, em particular a esquizofrenia.Esta monografia resume e discute as informações atualmente disponíveis sobre ainfluência do ambiente gastrointestinal no sistema nervoso central, com foco no eixomicrobiota-intestino-cérebro, os mecanismos subjacentes à comunicação bidirecional entre omicrobiota intestinal e o cérebro, o impacto que o eixo microbiota-intestino-cérebro podeter na esquizofrenia e novas estratégias terapêuticas, de modo a estabelecer perspetivas parao futuro. Com efeito, estudos recentes relataram que distúrbios neuropsiquiátricos, como aesquizofrenia estão associados a alterações do microbiota intestinal, um fenómeno conhecidopor disbiose. Alterações no microbiota intestinal induzem a ativação anormal das principaisvias de comunicação do eixo microbiota-intestino-cérebro através de mecanismosimunológicos, neurais, endócrinos, metabólicos e epigenéticos, levando a uma inflamaçãoexacerbada da mucosa intestinal e a alterações nas respostas ao stress.Em jeito de conclusão, o eixo microbiota-intestino-cérebro emerge agora como umanova estratégia terapêutica para prevenção e tratamento de distúrbios neuropsiquiátricos,incluindo a esquizofrenia. No entanto, mais estudos são necessários para que a visãotradicional da etiologia das doenças neuropsiquiátricas seja alterada, revelando o papel real doeixo microbiota-intestino-cérebro e o seu potencial como alvo de novos tratamentos.
The human gut microbiota (GM) comprise a large number of microorganisms, mostlybacteria, which co-evolved together with their human host. Recently, neuroscientist began toappreciate the influence of the dynamic interaction between gut microbes and hostgastrointestinal and central nervous system, the now known microbiota-gut-brain (MGB) axis.This bidirectional communication involves immune, neural, endocrine and metabolic pathways.Recent evidences suggest that microbiota may be associated with the pathogeny ofneuropsychiatric diseases, in particular schizophrenia (SCZ).This document summarizes and discusses currently available information on theinteraction between the gastrointestinal and central nervous system, focusing on the MGBaxis, the mechanisms underlying the bidirectional communication between the GM and thebrain, the impact that MGB axis may have in SCZ and novel therapeutic strategies, to establishfuture perspectives. Indeed, recent studies reported that neuropsychiatric disorders, such asSCZ, are associated with changes in the GM, a phenomenon known as dysbiosis. Alterationsin the GM induce aberrant activation of key pathways of MGB axis communication, includingimmune, neural, endocrine, metabolic and epigenetic mechanisms, leading to exacerbatedintestinal mucosal inflammation and altered responses to stress.The MGB axis may provide a novel therapeutic strategy for the prevention andtreatment of neuropsychiatric disorders, including SCZ. However, further research is requiredto change the traditional view of neuropsychiatric diseases, revealing the feasibility andpotential of the of MGB axis as a target for novel treatment.

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Norris, DJ. "Biomarkers and depression in Multiple Sclerosis : a longitudinal pilot study." Thesis, 2022. https://eprints.utas.edu.au/47632/.

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Depression is the most common psychiatric symptom experienced by people with multiple sclerosis (pwMS). Pathological inflammation, a characteristic hallmark of multiple sclerosis, has shown to alter peripheral and brain biomarkers implicated in the development and perpetuation of depression. However, few studies have examined this relationship in pwMS. The first study cross-sectionally examined the relationship between inflammatory biomarkers and depression in pwMS compared to healthy participants. The results suggested: (1) pwMS have higher levels of depressive symptoms than healthy participants; (2) proinflammatory cytokines do not differ across pwMS and healthy participants; and (3) some kynurenine-pathway metabolites differ and are involved in depression in pwMS. The second study examined the relationship between inflammatory biomarkers and depression in pwMS cross-sectionally and longitudinally (5-to-6-year period). The results suggested: (1) there are moderate cross-sectional relationships between some proinflammatory cytokines and kynurenine-pathway metabolites in pwMS at baseline; (2) some proinflammatory cytokines increase in pwMS overtime; and (3) no detected relationships between proinflammatory cytokines and depression in pwMS. The contribution of these findings toward the current understanding of inflammatory biomarkers in the pathogenesis and treatment of depression in pwMS is discussed. Future studies examining the role of biomarkers in depression in pwMS are required.

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Dissertations / Theses on the topic 'Gut-brain axis'

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