Academic literature on the topic 'Irritable bowel syndrome - Homeopathic treatment'

Doctor of Philosophy<br>Nineteenth century philosophy and anatomy regarded the nervous system as the only pathway of communication between the brain and body but now, research in the field of psychoneuroimmunology (PNI) has provided evidence to prove the age-old belief that there is a connection between the mind (or mental/emotional states) and the body. Researchers in PNI have now shown that the communication between the nervous and immune systems is bi-directional – i.e. there is a psychological reaction to physical disease and a somatic presentation of psychological disorders - and that the immune system, the autonomic nervous system, the endocrine system and the neuropeptide systems all communicate with each other by means of chemicals called messenger molecules or ligands. This paper outlines research into the treatment of Irritable Bowel Syndrome (IBS) with hypnotherapy, taking into account the mind-body connection and treating both the patient’s physiological and emotional/psychological symptoms rather than treating the physiological symptoms only. In other words, using a more holistic approach to the treatment of IBS. IBS is probably the most common functional gastrointestinal disorder encountered by both gastroenterologists and physicians in primary care. It is estimated that from 10% to 25% of the general population suffer from this condition and that it comprises about 30-50% of the gastroenterologists’ workload, yet the aetiology of IBS is unknown and, so far, there is no cure. Researchers are beginning to view IBS as a multi-faceted disorder in which there appears to be a disturbance in the interaction between the intestines, brain, and autonomic nervous system, resulting in an alteration in the regulation of bowel motility and/or sensory function. Most researchers agree that a subset of IBS sufferers have a visceral hypersensitivity of the gut or, more specifically, an increased perception of sensations in the gut. To date, studies of IBS have proposed previous gastroenteritis, small intestine bacterial overgrowth, psychosocial factors, a genetic contribution, and an imbalance of neurotransmitters as either possible causes or playing a part in the development of IBS. It is generally agreed that a patient’s emotional response to stress can exacerbate the condition. In section 1 of the thesis, the introduction, a detailed description and background appropriate to the study undertaken are provided, including aspects of epidemiology, diagnostic symptom criteria and clinical relevance of the Irritable Bowel Syndrome. Previous studies of various forms of treatment for IBS are discussed with the main emphasis being on treatment with hypnotherapy. All these therapies have concentrated on either mind or body treatments whereas this study demonstrates how hypnotherapy, and the use of imagery, addresses both mind and body. Finally, the rationale for the current study and the specific aims of the thesis are outlined. In section 2, the methodology and assessment instruments used in the clinical trial are discussed, as well as recruitment processes, research plan and timetable, and treatment schedule. Statistical analyses are provided and the main outcomes measures of the clinical trial, its limitations and scientific implications are addressed.

Bloating and distension remain important and intrusive manifestations of Irritable Bowel Syndrome. Although much of previous literature has used the the terms bloating and distension interchangeably, epidemiological data suggest that (i) distension is seen more commonly in IBS with constipation (IBS-C) compared with IBS with diarrhoea (JBS-D) patients (ii) bloating and distension seem to "correlate predominantly but not exclusively in IBS-C.

Background The importance of interactions between the host and gut microbiota in the pathogenesis of irritable bowel syndrome (IBS) is becoming increasingly apparent. Probiotics offer a potential new therapy for the treatment of IBS, but current results with these products are conflicting, largely as a result of poorly designed trials and non-standardisation of outcome measures. Aims The objective of this study was to assess the efficacy and safety of a liquid, multi-strain probiotic in the treatment of IBS. Methods A single-centre, randomised, double-blind, placebo-controlled trial of adult patients with symptomatic IBS. Patients received 12 weeks of treatment with the probiotic or placebo (1ml/kg/day). The primary efficacy measure was a change in the IBS symptom severity score (IBS-SSS) from baseline to week 12. A secondary outcome measure was a change in the IBS quality of life (IBS-QOL) score. Results A total of 186 patients were randomised and 152 patients completed the study. The mean difference in change in IBS symptom severity scores between the two groups was statistically significant (-35.0 (95% CI; -62.03, -7.87); p=0.01). Adverse events were mild and transient and no serious adverse events were reported. Conclusion The multi-strain probiotic is associated with an improvement in overall symptom severity in patients with IBS, is well tolerated and has a good safety profile.

Background and aims Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by abdominal pain and altered bowel habits. The societal costs of the disorder are significant, as are its negative effects on quality of life. Medical treatment options are limited, but psychological treatments such as hypnotherapy have proven to be effective. Important pathophysiological mechanisms include disturbances in brain processing of visceral sensation and expectation of visceral sensation. Increased sensation of stimuli (hypersensitivity) is present in a subset of IBS patients to distensions in the lower part of the gastrointestinal tract, indicating a probable important pathophysiological mechanism in IBS. The overall aim of the thesis was to further study the central pathophysiological mechanisms involved in IBS. Specifically, we aimed to identify differences in brain response to standardized repeated rectal distensions and expectation of these stimuli between IBS patients (with or without perceptual rectal hypersensitivity), and healthy controls. Furthermore, we aimed to investigate IBS patients´ brain responses to standardized rectal distensions and expectation of these stimuli after either a successful course hypnotherapy or educational intervention. Methods Functional magnetic resonance imaging (fMRI) data were acquired and analyzed from 15 IBS patients with visceral hypersensitivity, and 18 IBS patients with normal visceral sensitivity (papers I and II). In paper III, fMRI data were analyzed from IBS patients who reported significant symptom reduction after either a course of hypnotherapy, or an educational intervention. FMRI data from IBS patients and healthy controls were also compared. Results The findings reported in papers I and II suggest, that the differences in brain response between IBS patients with and without rectal hypersensitivity, can be explained by changes in brain response during the course of the experiment. Even though the brain responses were similar between groups during the early phase of the experiment, they became substantially different during the late phase. The IBS patients with rectal hypersensitivity demonstrated increased brain response in several brain regions and networks involved in visceral sensation and processing. In contrast, IBS patients with normal rectal sensitivity exhibited reduced brain response during the late phase of the experiment. As reported in paper III, similar symptom reduction was achieved for both treatments. The symptomatic improvement was associated with a reduction of response in the anterior insula, indicating an attenuated awareness of the stimuli. The hypnotherapy group had a reduction of response in the posterior insula, indicating less input to the brain, possibly due to changed activity in endogenous pain modulatory systems. In patients who reported significant symptom reduction following treatment, the brain response to rectal distension got more similar to that observed in healthy controls. Conclusions The results from papers I and II indicate that a subpopulation of IBS patients lacks the ability to habituate to repeated rectal distensions and expectation of these stimuli. Results from paper III indicate that the abnormal processing of visceral stimuli in IBS can be altered, and that the treatments probably had a normalizing effect on the central processing abnormality of visceral signals in IBS.

Irritable bowel syndrome (IBS) is characterized by chronic abdominal pain/discomfort along with altered bowel habits, which accounts for a large proportion of gastrointestinal (GI) disorders worldwide. While psychiatric distress like depression is one of the most frequent comorbidities in IBS patients, which not only influences the quality of life, it also leads to a substantial economic burden and inefficient treatment in IBS patients. Inflammation, altered activities of the HPA axis, aberrant central neuroplasticity and neurotransmission have been highly regarded as pathogenic factors of the depression. Whereas, in recent years, dysfunctions in the gut microbial community has been increasingly discovered to provoke depression disorder. Considering that gut dysbiosis plays causal role in IBS progression, dysfunction of the gut microbiota has been speculated for contributing to the depressive symptoms in IBS (IBS-DP) patients. However, whether and how gut dysbiosis affecting IBS-DP patients remain unclear. We hypothesized that gut microbiota changes contribute to the development of IBS-DP and the change of gut microbiota-driven metabolites induces the structural and/or functional changes of the central nervous system (CNS), thus resulting in the development of IBS-DP. In this thesis, IBS patients with and without depression and animal models of IBS have been systematically studied, to investigate whether gut dysbiosis mediates depressive disorder in IBS. Firstly, we conducted a cross-sectional study involving the distribution of depressive disorder in the IBS population of Hong Kong. According to this survey, we found that there is 36.6% (135/369) of IBS patients showed symptoms of depression. The severity of depressive symptoms was positively associated with the harshness of visceral pain and bloating signatures in IBS patients. Secondly, in comparison to the non-depression of IBS (IBS-ND) group, faecal metagenomic results unveiled the disrupted gut microbiota in IBS-DP patients, mainly with the deficiency of several beneficial bacterial groups, including Akkermansia, Bifidobacterium and Eubacterium, whereas the gut microbiota profile between IBS-ND patients and healthy controls (HCs) showed no significant changes. Compared with HCs, enzyme-linked immunosorbent Assay (ELISA) results showed higher levels of serum IL-1β, IL-6, and TNF-a in IBS-DP patients, indicating a low-grade peripheral inflammation in IBS-DP patients. Moreover, the abundance of Akkermansia muciniphila (A. muciniphila), was negatively correlated with Hamilton Rating Scale for Depression (HAMD) score and Zung Self-Rating Depression Scale (SDS) score, IL-1β, TGF-β, and TNF-a in IBS-DP patients. These findings indicate that gut dysbiosis, especially deficiency in A. muciniphila, is related to the depressive symptoms and inflammation in IBS-DP patients. Thirdly, in a neonatal maternal separation (NMS) rat model, behavioural tests such as colorectal distention (CRD) test, open field test (OFT), forced swimming test (FST), and sucrose preference test (SPT) results showed visceral hypersensitivity and depression symptoms in rats. These results indicate that the model can successfully mimic the visceral hyperalgeisa and the depression-like behaviour of IBS-DP. Immunohistochemical analysis showed an altered morphology and decreased the quantity of astrocytes in the hippocampus of NMS rats when compared with that of controls. More importantly, the mRNA expressions of genes related to Astroglial glutamate transmission including glutamate transporters (GLTs), glutamate receptors, and also glutamate-related exchangers, as well as astrocyte biomarker glial fibrillary acidic protein (GFAP), which are mediated with chronic inflammation and/or stress, were decreased in NMS rats when compared with the control group. These results indicate that impaired astroglial glutamate neurotransmission in NMS rats. Furthermore, pseudo-GF rats with faecal microbiota transplantation (FMT) of NMS microbiota were also conducted, and results showed that the association of A. muciniphila deficiency, depressive-like behaviours and impaired astroglial glutamate neurotransmission were repeated in the rat recipients. These results indicate a causal relationship between NMS microbiota and depressive phenotype, involving dysfunction of the astrocyte- glutamate pathway. Fourthly, to further verify the role of A. muciniphila in NMS microbiota-induced depressive phenotype and impaired astrocytic glutamate pathway, we orally administered live and heat-killed A. muciniphila bacteria in NMS adult rats. A. muciniphila (108 CFU in 1mL PBS) was administered once-daily for four consecutive weeks. Besides, rifaximin and fluoxetine were also separately treated in NMS rats as control groups. Rifaximin is a broad-spectrum GI-specific antibiotic that is commonly used for IBS treatment, and fluoxetine, a selective serotonin re-uptake inhibitor, is one of the most frequently prescribed anti-depressants. The results showed that A. muciniphila efficiently improved depressive-like behaviours, attenuated the impaired astrocytic glutamate neurotransmission, as well as restored the normal morphology and number of astrocytes in the hippocampus of NMS rats. While rifaximin-treated rats only exhibited amelioration of visceral pain, and fluoxetine group mainly performed antidepressant effect, without any significant change in astrocytic glutamate neurotransmission impairment. These results demonstrate that A. muciniphila improves depressive symptoms in IBS phenotype and ameliorate astroglial-glutamatergic pathway dysfunction. Whether and how A. muciniphila modulates astroglial glutamate transmission, therefore leading to the improvement of depressive symptom in IBS, remains to be further investigated. Taken together, the works of this thesis, combining both clinical and animal studies reveal that gut dysbiosis, particularly deficiency of A. muciniphila, contributes to the development of IBS-DP via regulating the astroglial glutamatergic pathway. This study gives a different direction to microbial-guided therapy for the IBS-DP patients in the future

Irritable bowel syndrome (IBS) is a condition where abdominal pain, diarrhoea, constipation, gas distension and/or variability in the bowel habit are experienced. It has been suggested that the gut microflora may be involved in this condition and that an 'abnormal' colonic fermentation may provoke the symptoms ofIBS. In this study, the faecal flora of 11. IBS patients was compared with that of 11 healthy individuals quantitatively using fluorescence in situ hylJridisation (FISH) and· traditional plating techniques, as well as qualitatively using denaturating gradient gel electrophoresis (DGGE). It was found that IBS patients had lower total . . ./ bacterial counts, bifidobacteria, lactobacilli, bacteroides and clostridia than seen in healthy individuals. DGGE also showed differences between illS and healthy samples, especially in relation to stability ofthe microflora over time. A synbiotic version ofLactobacillus plantarum NCIMB 41114 with seven different prebiotics was tested in batch culture fermenters using faecal samples from IBS donors. From all the combinations GOS-synbiotic was chosen sirc~ it enhanced the . . growth of the probiotic and was found to be more effective in 'normalising' the . .~ faecal flora in IBS. This synbiotic combination was used in gut model· systems using faecal samples from donors belonging to different IDS subgroups. The results showed that administration of the synbiotic impacted the specific IBS subgroups .. differently, but modulated the rnicroflora towards selective stimulation of bifidobacteria and lactobacilli. In the last part of the study the amount of gas produced from IBS faecal flora during fermentation was compared to that ofhealthy faecal flora. The IDS flora produced more cumulative gas and had greater rates of production than the healthy flora. Administration of the synbiotic reduced gas production in all systems (IBS and healthy). Taken together, these observations help to define dietary management strategies, based on the gut flora and its activities, aimed towards improving IBS symptomology.

Background: IBS is the most common functional gastrointestinal disorders and affects approximately 10-20 % of the general population and is widespread in all societies and socio-economic groups. Although the disorder does not have a life-threatening course, it still seriously affects the patients in their everyday life. Aim: The general aims of this thesis were to estimate the occurrence of irritable bowel syndrome in the general population and to achieve a better understanding of present treatment of this disorder and impact on every-day life in those suffering from IBS. Material and methods: The LIPS study comprises two parts. Part I was a retrospective register study where the data collection was based on computerised medical records at three selected Primary Health Care centres in a defined region. Part II was a population based case-control study. The identified IBS cases from part I constitute the cases, while their control groups were randomly selected from the population census register in the same area as the cases. Data in part II were collected by means of a postal questionnaire to cases and controls. The study was conducted in Linköping, a city located in the south-east of Sweden with 135 000 inhabitants. Results: The female IBS patients reported lower influence on planning their work and working hours as well as fewer opportunities to learn new things at their work compared to their controls, even after adjustments in multiple logistic regressions for potential confounders like; mood, sleeping problems and perceived health. The female IBS patients had considerably lower HRQOL in all dimensions compared to their controls, even when compared to male patients. Younger female IBS cases (18-44 years) reported lower mental health on the SF-36 scale than the older IBS female cases (p=0.015). In the multivariate analysis these variables, lack of influence on planning the work, family history of IBS, anxiety and sleeping disturbance displayed an association with being diagnosed with IBS in women. In men, lack of influence on working pace, family history of IBS was associated with an IBS diagnosis.The consultation incidence of IBS in part I was 3.4 (95% CI 3.20-3.70) per 1000 person-years for all IBS cases, among females; the incidence rate was 4.6 per 1000 person-years (95% CI 4.16-4.97) and males; 2.3 per 1000 person-years (95% CI 2.01-2.59). The dominating pharmacological treatment prescribed for abdominal complaints were fibre and bulking laxatives agents as well as acid suppressive drugs. These variables had an independent impact on the probability of a follow-up consultation; diagnosed co-morbidity besides the IBS diagnosis, rectoscopy ordered and laboratory tests ordered. Conclusions: IBS patients identified in primary care are significantly affected in their working-life compared to individuals in the general population. Especially female IBS-patients report lower decision latitude at work and they also appear to have a particularly impaired psychosocial functioning in their every day life and impaired HRQOL. Factors associated with IBS diagnosis among females are anxiety as well as family history of IBS and lack of co-determination at work. The incidence rate of IBS was 3.4 per 1000 person-years which increased with age and with an overrepresentation of females. IBS patients did not appear to be heavy utilisers of primary care and those who attended were treated by their GP without further consultation. The strongest predictors for having a follow-up consultation were diagnosed co-morbidity, rectoscopy and laboratory tests ordered<br>Figure on page 8 reprinted from Lancet 360(9332), Nicholas, J Talley and Robin Spiller, "Irritable bowel syndrome: a little understood organic bowel disease?", pp. 555-564, Copyright 2006 with permission from Elsevier. On the day of the public defence of the doctoral thesis, the status of articles III and IV was Submitted.