Academic literature on the topic 'Gut microbiota, mental health, dysbiosis'

ABSTRACT Normally in health, the commensal gut microbiota lives in a perfectly symbiotic relationship with the host. Initial bacterial colonization occurs through the maternal vaginal/fecal flora and oral feeding. When this symbiotic relationship is lost due to several factors, the condition is known as “dysbiosis.” Dysbiosis is associated with the pathogenesis of intestinal disorders, such as inflammatory bowel disease, irritable bowel syndrome (IBS), and coeliac disease, but recent studies have shown that it has also been implicated in extraintestinal disorders, such as allergy, asthma, cardiovascular disease, obesity, autoimmune diseases, inflammatory diseases, and some mental disorders and cancers. The proposed mechanism for the development of such disorders is disruption of the pivotal mutual relationship between the gut microbiome, the metabolic products produced by them, and the host immune response. In this review article, we would like to highlight the role of gut microbiota in the development of extraintestinal diseases. How to cite this article: Chandra A, Ray AK, Chakraborty U, et al. Gut Microbiota and Extraintestinal Disorders: Are They Interrelated? Bengal Physician Journal 2020;7(1):8–11.

Breast cancer is the most frequently diagnosed cancer in women worldwide. The disease and its treatments exert profound effects on an individual’s physical and mental health. There are many factors that impact an individual’s risk of developing breast cancer, their response to treatments, and their risk of recurrence. The community of microorganisms inhabiting the gastrointestinal tract, the gut microbiota, affects human health through metabolic, neural, and endocrine signaling, and immune activity. It is through these mechanisms that the gut microbiota appears to influence breast cancer risk, response to treatment, and recurrence. A disrupted gut microbiota or state of ‘dysbiosis’ can contribute to a biological environment associated with higher risk for cancer development as well as contribute to negative treatment side-effects. Many cancer treatments have been shown to shift the gut microbiota toward dysbiosis; however, the microbiota can also be positively manipulated through diet, prebiotic and probiotic supplementation, and exercise. The objective of this review is to provide an overview of the current understanding of the relationship between the gut microbiota and breast cancer and to highlight potential strategies for modulation of the gut microbiota that could lead to improved clinical outcomes and overall health in this population.

Gut microbiota dysbiosis is a recognized contributing factor to many noncommunicable diseases, but more evidence is still needed to illustrate its causative impact on mental and brain health disorders and mechanism(s) for targeted mitigation.

Abstract The microbial communities colonizing the gastrointestinal tract of vertebrate hosts exist in symbiosis with their host, providing a wide array of functions that confer benefit to the collective superorganism. Intuitively, disruptions in microbial community structure can lead to deleterious host effects, and multiple associations have been made between gut inflammatory conditions and dysbiosis. Considering the myriad mechanisms of bi-directional communication between the gut microbiota and host autonomic nervous system, it is not surprising that the gut microbiota is now implicated as a factor in several behavioral, cognitive, and neuro-psychological conditions affecting people. While gut microbiomes have co-evolved with (and are very specific for) their cognate hosts, the functions provided by the communities are highly conserved, suggesting that the same microbiome-induced effects observed in people may also affect companion animals like horses. This presentation will show data generated in a range of host species including zebrafish, rodents, and horses, demonstrating the influence of the gut-brain axis on behavior, and physical and mental health. The objective is to provide listeners a new appreciation for the physiological, and perhaps clinical, influence of the gut microbiota, and implications for clinical practices such as antibiotic usage and feeding changes.

Depression is a highly common mental disorder, which is often multifactorial with sex, genetic, environmental, and/or psychological causes. Recent advancements in biomedical research have demonstrated a clear correlation between gut dysbiosis (GD) or gut microbial dysbiosis and the development of anxiety or depressive behaviors. The gut microbiome communicates with the brain through the neural, immune, and metabolic pathways, either directly (via vagal nerves) or indirectly (via gut- and microbial-derived metabolites as well as gut hormones and endocrine peptides, including peptide YY, pancreatic polypeptide, neuropeptide Y, cholecystokinin, corticotropin-releasing factor, glucagon-like peptide, oxytocin, and ghrelin). Maintaining healthy gut microbiota (GM) is now being recognized as important for brain health through the use of probiotics, prebiotics, synbiotics, fecal microbial transplantation (FMT), etc. A few approaches exert antidepressant effects via restoring GM and hypothalamus–pituitary–adrenal (HPA) axis functions. In this review, we have summarized the etiopathogenic link between gut dysbiosis and depression with preclinical and clinical evidence. In addition, we have collated information on the recent therapies and supplements, such as probiotics, prebiotics, short-chain fatty acids, and vitamin B12, omega-3 fatty acids, etc., which target the gut–brain axis (GBA) for the effective management of depressive behavior and anxiety.

IntroductionThere is a bi-directional biochemical communication pathway between the gastrointestinal tract and the central nervous system, referred to as the “gut–brain axis”. Studies show that bacteria in the gastrointestinal tract, including commensal, probiotic, or pathogenic, can affect brain’s function. Since there is a symbiotic relationship between gut microbiota and the brain, changes in its composition can lead to dysbiosis, which plays a role in many psychiatric disorders, such as depression and anxiety, and therefore becomes a potential therapeutic target.ObjectivesTo examine data from recent studies regarding the gut-brain axis and its relationship with psychiatric disorders, such as depression and anxiety.MethodsReview of the most recent literature regarding the gut-brain axis and its relationship with depression and anxiety disorders. The research was carried out through the MedLine, PubMed, UptoDate, ScienceDirect, SciELO and SpringerLink databases, using the terms “gut-brain axis”, “depression” and “anxiety”, until December 2020.Results There is a relationship between dysbiosis of microbiota and some psychiatric disorders, particularly depression. Symbiosis may be restored by purposefully manipulate the gut microbiota using therapies such as probiotics, therefore enhancing beneficial bacteria in the gastrointestinal tract and improving symptoms of depression.ConclusionsAlthough probiotics can be used in the treatment of depression, further research is needed in order to carefully determine parameters such as the duration of treatment, dosage and drug interactions. Nonetheless, a better understanding of the gut-brain axis may arise new approaches on how we prevent and treat mental illnesses.DisclosureNo significant relationships.

The gut microbiota is extremely important for the health of the host across its lifespan.Recent studies have elucidated connections between the gut microbiota and neurological diseaseand disorders such as depression, anxiety, Alzheimer’s disease (AD), autism, and a host of otherbrain illnesses. Dysbiosis of the normal gut flora can have negative consequences for humans,especially throughout key periods during our lifespan as the gut microbes change with age in bothphenotype and number of bacterial species. Neurologic diseases, mental disorders, and euthymicstates are influenced by alterations in the metabolites produced by gut microbial milieu. Weintroduce a new concept, namely, the mycobiota and microbiota-gut-brain neuroendocrine axis anddiscuss co-metabolism with emphasis on means to influence or correct disruptions to normal gutflora throughout the lifespan from early development to old age. These changes involveinflammation and involve the permeability of barriers, such as the intestine blood barrier, the blood–brain barrier, and others. The mycobiota and microbiota–gut–brain axis offer new research horizonsand represents a great potential target for new therapeutics, including approaches based aroundinflammatory disruptive process, genetically engineered drug delivery systems, diseased cellculling “kill switches”, phage-like therapies, medicinal chemistry, or microbial parabiosis to namea few.

Astrocytes are essential for maintaining the homeostasis of the central nervous system (CNS). Astrocytic dysfunction has been implicated in the progression of several neurodegenerative and psychiatric diseases; however, a multitude of factors and signals influencing astrocytic activity have not been entirely elucidated. Astrocytes respond to local signals from the brain, but are also indirectly modulated by gut microbiota. Previous studies revealed that most of the CNS diseases triggered by astrocytic dysfunction are closely associated with the dysbiosis of gut microbiome. Emerging data from preclinical and clinical studies suggest that the maturation and functioning of astrocytes rely on gut microbiota, which plays a pivotal role in the decrease of astrocytic activation and may alleviate symptoms of brain diseases. Herein, we discuss the most recent advances concerning the complex connections between astrocytes and gut microbiota, which are involved in the immune, neurotransmission and neuroendocrine pathways. Deciphering these pathways will facilitate a better understanding of how perturbed gut microbiota contributes to the dysfunction of astrocytes and open therapeutic opportunities for the treatment of brain diseases.

Abstract Background Chronic pain is frequently comorbid with depression in clinical practice. Recently, alterations in gut microbiota and metabolites derived therefrom have been found to potentially contribute to abnormal behaviors and cognitive dysfunction via the “microbiota–gut–brain” axis. Methods PubMed was searched and we selected relevant studies before October 1, 2019. The search keyword string included “pain OR chronic pain” AND “gut microbiota OR metabolites”; “depression OR depressive disorder” AND “gut microbiota OR metabolites”. We also searched the reference lists of key articles manually. Results This review systematically summarized the recent evidence of gut microbiota and metabolites in chronic pain and depression in animal and human studies. The results showed the pathogenesis and therapeutics of chronic pain and depression might be partially due to gut microbiota dysbiosis. Importantly, bacteria-derived metabolites, including short-chain fatty acids, tryptophan-derived metabolites, and secondary bile acids, offer new insights into the potential linkage between key triggers in gut microbiota and potential mechanisms of depression. Conclusion Studying gut microbiota and its metabolites has contributed to the understanding of comorbidity of chronic pain and depression. Consequently, modulating dietary structures or supplementation of specific bacteria may be an available strategy for treating chronic pain and depression.

This thesis investigates how air pollution, both natural and anthropogenic, affects changes in the proximal small intestine and ileum microbiota profile, as well as intestinal barrier integrity, histological changes, and inflammation. APO-E KO mice on a high fat diet were randomly selected to be exposed by whole body inhalation to either wood smoke (WS) or mixed vehicular exhaust (MVE), with filtered air (FA) acting as the control. Intestinal integrity and histology were assessed by observing expression of well- known structural components tight junction proteins (TJPs), matrix metallopeptidase-9 (MMP-9), and gel-forming mucin (MUC2), as well known inflammatory related factors: TNF-α, IL-1β, and toll-like receptor (TLR)-4. Bacterial profiling was done using DNA analysis of microbiota within the ileum, utilizing 16S metagenomics sequencing (Illumina miSeq) technique. Overall results of this experiment suggest that air pollution, both anthropogenic and natural, cause a breach in the intestinal barrier with an increase in inflammatory factors and a decrease in beneficial bacteria. This evidence suggests the possibility of air pollution being a potential causative agent of intestinal disease as well as a possible contributing mechanism for induction of systemic inflammation.

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2015
A composição e função da microbiota intestinal tem sido objecto de bastante escrutínio, primeiro através do uso de técnicas dependentes de cultura microbiológica e, mais recentemente, utilizando técnicas de sequenciação que vieram permitir um melhor conhecimento acerca dessa mesma composição e diversidade complexa microbiana. Estes avanços nas tecnologias metagenómicas permitiu saber a composição da flora intestinal mas pouco é ainda sabido sobre a fisiologia e o impacto da microbiota no hospedeiro humano e na saúde, inclusivamente no cérebro. Sem dúvida, entender a influência da microbiota gastrointestinal na saúde humana tem sido um dos temas mais entusiasmantes na medicina contemporânea. Tendo em conta a falta de uniformização no que diz respeito aos métodos utilizados nos diferentes estudos, os resultados díspares face a amostras reduzidas e a escassez de estudos em seres humanos, a autora propõe uma revisão dirigida à evidência já existente face ao impacto da flora gastrointestinal nos estados de humor e desenvolvimento neurocognitivo, assim como face ao uso de psicobióticos no tratamento ou profilaxia dessas mesmas condições. Resumir-se-ão a importância da microbiota humana, os principais mecanismos (imunológicos, endocrinológico e neurológicos), através dos quais a microbiota gastrointestinal influencia o Sistema Nervoso Central o papel do Sistema Nervoso Entérico nessa relação e o uso de probióticos, prebióticos como psicobióticos. Da exposição da evidência relativa a essas temáticas, tentar-se-ão tirar conclusões sobre o uso de psicobióticos como arma terapêutica no tratamento e/ou profilaxia de patologias psiquiátricas como a depressão major e as perturbações do espectro autista.
The composition and function of gut microbiota hás been object of intense scrutiny, first using techniques dependents of microbiological culture and, more recently, using sequencing techniques that made possible a better understanding of the gut microbial complex composition and diversity. These technical advances on metagenomics made able to know the gut flora composition but little is still known about the physiology and impact of microbiota on the human host and its health, including on the brain. There is no doubt that understanding the influence of gut microbiota on human health has been one subject of the most contemporary exciting in medicine. Taking in consideration the lack of uniformization in methods adopted by the different studies, the not concordant results, the small samples and the lack of studies in humans, the author purposes to review the existing evidence of the impact of gut microbiota on the humour states and neurocognitive development, and as well the use of psychobiotics in the treatment and prophilaxy of those conditions. Will be pointed out the significance of human gut microbiota, the main mechanisms (immunological, endocrinological and neurological) by which the gut microbiota influences the Central Nervous System, the role of Enteric Nervous System and the use of probiotics, prebiotics as psychobiotics. By the explanation of those subjects, we will try to take some conclusions about the use of psychobiotics as a therapeutical weapon on the treatment and/or prophilaxy of psychiatric pathologies as major depression and autistic spectrum pathologies.

En raison des avancées thérapeutiques, plus de 90% des enfants atteints de la leucémie lymphoblastique aiguë (LLA) survivent à la maladie. Cependant, plusieurs survivants sont à risque de développer des morbidités à long terme, causées par le cancer et ses traitements, surtout que ces derniers sont administrés pendant une période cruciale du développement. Les effets néfastes à long terme comprennent notamment des désordres cardiométaboliques tels que l’obésité, la dyslipidémie et le diabète de type 2. Bien que leur étiologie précise ne soit pas entièrement comprise, certains mécanismes sous-jacents au développement des complications à long terme ont été proposés. Étonnamment, peu d’études ont évalué la relation entre l’alimentation et les complications cardiométaboliques chez les survivants du cancer pédiatrique. Dans la population générale, de mauvaises habitudes alimentaires ont été associées à l’incidence des composantes du syndrome métabolique et de l’athérosclérose. Également, il a été démontré que le microbiote intestinal joue un rôle prépondérant dans la pathogenèse et la progression des perturbations cardiométaboliques dans la population générale. Ce rôle a été peu étudié dans la population survivante de cancer, alors que les traitements pourraient mener à des modifications importantes de la composition, de la diversité et de la fonction du microbiote intestinal. Nos travaux ont visé l’étude de l’état de santé cardiométabolique et nutritionnelle de survivants de la LLA de l’enfant et la détermination des associations entre les deux. De plus, nous avons exploré les mécanismes impliquant le microbiote intestinal dans le développement des complications cardiométaboliques. L’ensemble des travaux a été réalisé dans le cadre de l’étude PETALE (Prévenir les effets tardifs des traitements de la leucémie lymphoblastique aiguë) au Centre hospitalier universitaire Sainte-Justine à Montréal. Nos résultats ont mis en évidence la forte prévalence des complications cardiométaboliques chez les adolescents et les jeunes adultes survivants de la LLA pédiatrique. Ils ont aussi confirmé leur risque cardiovasculaire accru par rapport à la population générale canadienne, plus particulièrement ceux ayant été exposés à la radiothérapie crânienne. En outre, des altérations des profils des lipoprotéines et apolipoprotéines, indicateurs d’une augmentation du risque d’athérosclérose, ont été identifiées. Nous avons observé que les survivants respectent peu les recommandations alimentaires et leurs mauvaises habitudes alimentaires affectent leur état nutritionnel et métabolique. Nos résultats confirment l’association d’un régime alimentaire de qualité et une meilleure santé cardiométabolique des survivants. Nous avons identifié une association inverse entre un apport élevé de macro- et micronutriments spécifiques (protéines, sélénium, zinc, cuivre, riboflavine et niacine) ainsi que de viande et le risque de présenter des taux de HDL-C faibles chez les survivants tandis que la restauration rapide était associée positivement avec ce risque. Il est à noter que malgré un faible apport en vitamine D, la prévalence de l’insuffisance ou de la carence en vitamine D n’est pas plus importante chez les survivants que dans la population générale canadienne. Nous avons identifié des associations entre des biomarqueurs plasmatiques de l’inflammation viscérale et de l’endotoxémie et les complications cardiométaboliques chez les survivants de la LLA pédiatrique. Nous avons également mis en évidence la relation entre l’endotoxémie métabolique, l’inflammation et la présence de complications cardiométaboliques. Une revue de littérature a permis de détailler le rôles émergent de la dysbiose intestinale dans les complications métaboliques chez les survivants. Dans nos travaux exploratoires, nous avons constaté que, dans une grande proportion des survivants métaboliquement non sains, il y avait une abondance réduite de familles de bactéries ayant des rôles protecteurs envers l’endotoxémie métabolique. Nous avons aussi démontré la faisabilité d’utiliser un modèle murin xénogénique de LLA pour étudier les mécanismes du développement des complications cardiométaboliques. L’identification de biomarqueurs et de mécanismes biologiques ainsi qu’une meilleure compréhension de la manière dont le régime et les composantes alimentaires peuvent affecter les survivants de la LLA de l’enfant permettra le développement de stratégies de prévention pour minimiser les séquelles à long terme, améliorer le suivi des patients et optimiser la qualité de vie de cette population à haut risque.
As a result of therapeutic advances, more than 90% of children with acute lymphoblastic leukemia (ALL) survive the disease. However, many survivors are at risk of developing long-term morbidities caused by the cancer and its treatments, especially since these are administered during a crucial period of their development. Long-term adverse effects include cardiometabolic disorders such as obesity, dyslipidemia and type 2 diabetes. Although their precise etiology is not fully understood, some mechanisms underlying the development of long-term complications have been proposed. Surprisingly, few studies have evaluated the relationship between diet and cardiometabolic complications in childhood cancer survivors. In the general population, poor dietary habits are associated with the incidence of metabolic syndrome components and atherosclerosis. Also, the intestinal microbiota appears to play a major role in the pathogenesis and progression of cardiometabolic disturbances in the general population. This role has been poorly studied in cancer survivor populations, where treatments could lead to significant changes in intestinal microbiota composition, diversity and function. We studied the cardiometabolic and nutritional health status of childhood ALL survivors and determined the associations between the two. In addition, we explored the intestinal microbiota as an underlying mechanism of cardiometabolic complication development. This work was carried out as part of the PETALE (Preventing Late Effects of Acute Lymphoblastic Leukemia Treatments) study at the Centre hospitalier universitaire Sainte-Justine in Montreal. Our results highlighted the high prevalence of cardiometabolic complications in adolescent and young adult survivors of childhood ALL. They also confirmed their increased cardiovascular risk compared to the general Canadian population, particularly those exposed to cranial radiotherapy. In addition, alterations in lipoprotein and apolipoprotein profiles, indicative of an increased risk of atherosclerosis, were identified. We observed that survivors have poor compliance with dietary recommendations and that poor eating habits affect their nutritional and metabolic status. Our results confirm the association of diet quality and a better survivors’ cardiometabolic health. We identified an inverse association between a high intake of specific macro- and micronutrients (protein, selenium, zinc, copper, riboflavin and niacin) as well as meat and the risk of having low HDL-C levels in survivors, while fast food was positively associated with this risk. It should be noted that despite low vitamin D intake, the prevalence of vitamin D insufficiency or deficiency is no greater among survivors than in the general Canadian population. We identified associations between plasma biomarkers of visceral inflammation and endotoxemia and cardiometabolic complications in childhood ALL survivors. We also demonstrated the relationship between metabolic endotoxemia, inflammation and the presence of cardiometabolic complications. A review of the literature detailed the emerging role of intestinal dysbiosis in the metabolic sequelae found in survivors. In our exploratory work, we found that, in a large proportion of metabolically unhealthy survivors, there was a reduced abundance of bacteria families with protective role towards endotoxemia. We also demonstrated the feasibility of using a xenogenic mouse model of ALL to study the mechanisms explaining the development of cardiometabolic complications. The identification of biomarkers and biological mechanisms and a better understanding of how diet and nutritional components may affect survivors of childhood ALL will allow the development of prevention strategies to minimize long-term sequelae, improve patient follow-up and optimize the quality of life of this high-risk population.

A large body of research has shown the presence of a complex pathway of communication between gut and brain. It is now recognized that, through this pathway, microbiota can influence intestinal homeostasis and modulate brain plasticity in normal and pathological conditions. This chapter provides an overview of preclinical and clinical evidence supporting the possible mechanisms whereby microbiota can influence gastrointestinal function and stress-related behaviour. Since normalization of gut flora can prevent changes in behaviour, the authors further postulate that the gut–brain axis might represent a possible target for pharmacological and dietary strategies aimed at improving intestinal and mental health.

Colitis-associated cancers are a metastatic form of inflammatory bowel disease considered a vital health associated risk factor causing the death of approximately five lacs people every year throughout the world. There are trillions of bacteria that are associated with our gut as a part of our healthy microbiome. The microbiota plays a plethora of important role in determining the normal physiological processes of the cells and, subsequently, the body. The imbalance in microbiome diversity (dysbiosis) due to abnormal dietary habitats, hectic lifestyle, and other factors thus alters the normal physiological processes of the body, thereby causing several chronic diseases. Therefore, it is essential to maintain the homeostasis between the host and their gut microbiome. So, based on the facts mentioned above, this chapter is entirely devoted to providing an overview of colitis-associated cancer and their relation with the dysbiosis of a healthy microbiome. Moreover, the mechanism involved in the development of colorectal cancer and its preventive insights has also been addressed.

Non-alcoholic fatty liver disease (NAFLD) affects 20–30% of the population, with an increased prevalence in industrialized regions. Some patients with NAFLD develop an inflammatory condition termed non-alcoholic steatohepatitis (NASH) that is characterized by hepatocellular injury, innate immune cell-mediated inflammation, and progressive liver fibrosis. In clinical practice, abdominal imaging, which reveals hepatic steatosis, is sufficient for NAFLD diagnosis if other diseases have been rejected. However, a liver biopsy is needed to differentiate NASH from simple steatosis. Therapeutic strategies used to treat obesity and metabolic syndrome improve NAFLD, but there is no specific treatment effective for NASH. The gut microbiota (GM) is composed of millions of microorganisms. Changes in the GM have a significant impact on host health. Intestinal dysbiosis is an imbalance in the GM that can induce increased permeability of the epithelial barrier, with migration of GM-derived mediators through portal vein to the liver. These mediators, such as lipopolysaccharides, short-chain fatty acids, bile acids (BAs), choline, and endogenous ethanol, seem to be involved in NAFLD pathogenesis. Given this evidence, it would be interesting to consider GM-derived mediator determination through omics techniques as a noninvasive diagnostic tool for NASH and to focus research on microbiota modulation as a possible treatment for NASH.