Gut microbiota and irritable bowel syndrome

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that poses a significant health concern. Although its etiology remains unknown, there is growing evidence that gut dysbiosis is involved in the development and exacerbation of IBS. Previous studies have reported altered microbial diversity, abundance, and composition in IBS patients when compared to controls. However, whether dysbiosis or aberrant changes in the intestinal microbiota can be used as a hallmark of IBS remains inconclusive. We reviewed the literatures on changes in and roles of intestinal microbiota in relation to IBS and discussed various gut microbiota manipulation strategies. Gut microbiota may affect IBS development by regulating the mucosal immune system, brain–gut–microbiome interaction, and intestinal barrier function. The advent of high-throughput multi-omics provides important insights into the pathogenesis of IBS and promotes the development of individualized treatment for IBS. Despite advances in currently available microbiota-directed therapies, large-scale, well-organized, and long-term randomized controlled trials are highly warranted to assess their clinical effects. Overall, gut microbiota alterations play a critical role in the pathophysiology of IBS, and modulation of microbiota has a significant therapeutic potential that requires to be further verified.     

Bacterial flora in irritable bowel syndrome: role in pathophysiology, implications for management

Irritable bowel syndrome (IBS) may, in part at least, result from a dysfunctional interaction between the indigenous flora and the intestinal mucosa which, in turn, leads to immune activation in the colonic mucosa. Some propose a role for bacterial overgrowth as a common causative factor in the pathogenesis of symptoms in IBS; other evidence points to more subtle qualitative changes in the colonic flora; both hypotheses remain to be confirmed but the likelihood that bacterial overgrowth will prove to be a major factor in IBS now seems remote. Nevertheless, short-term therapy with either antibiotics or probiotics does seem to reduce symptoms among IBS patients. It seems most likely that the benefits of antibiotic therapy are mediated through subtle and, perhaps, localized, quantitative and/or qualitative changes in the colonic flora. How probiotics exert their effects remain to be defined but an anti-inflammatory effect seems likely. While this approach to the management of IBS is in its infancy, it is evident that manipulation of the flora, whether through the administration of antibiotics or probiotics, deserves further attention in IBS.     

Post-infectious irritable bowel syndrome in patients with Shigella infection

BACKGROUND AND AIMS: Bacterial gastroenteritis has been known as a risk factor of irritable bowel syndrome (IBS). Several risk factors of post-infectious IBS (PI-IBS) have been documented. The aims of this study were to verify the role of bacterial gastroenteritis in the development of IBS and the risk factors for the development of PI-IBS. The clinical course of PI-IBS was also investigated. METHODS: We recruited 143 patients with shigellosis during its outbreak and 113 controls. Both groups were followed up for 12 months. Bowel symptoms were evaluated by use of questionnaires at 3, 6 and 12 months after the initial recruitment. RESULTS: Complete data were obtained from 101 patients (70.6%) and 102 healthy controls (90.3%). At 12 months, 15 patients and six controls had IBS (adjusted OR; 2.9, 95% CI; 1.1-7.9). Of the 15 patients, five had IBS symptoms consistently for 12 months, three did not have IBS symptoms initially and seven had fluctuating bowel symptoms. The duration of diarrhea was an independent risk factor of PI-IBS. CONCLUSIONS: Bacterial gastroenteritis is a risk factor of IBS and the duration of diarrhea as the index of severity of initial illness is an independent risk factor of PI-IBS. The clinical course of PI-IBS is variable over the 1 year of follow-up.     

Differences of microbiota in small bowel and faeces between irritable bowel syndrome patients and healthy subjects

Objective Several studies suggested that colonic microbiota have impacts on irritable bowel syndrome (IBS) patients. However, the knowledge about the association of small intestine (SI) microbiota with IBS is limited. We aimed to investigate the gut microbiota composition of SI and stool in IBS patients. Materials and methods Biopsies of jejunum mucosa by balloon-assisted enteroscopy and faecal samples from 28 IBS patients and 19 healthy controls were analysed by next-generation sequencing method. Results The three major phyla in SI microbiota of case/control groups were Proteobacteria (32.8/47.7%), Bacteroidetes (25.2/15.3%), and Firmicutes (19.8/11.2%), and those of stool were Bacteroidetes (41.3/45.8%), Firmicutes (40.7/38.2%), and Proteobacteria (15.4/7.1%). Analysis based on the family level, IBS patients had a higher proportion of Veillonellaceae (mean proportion 6.49% versus 2.68%, p?=?0.046) in stool than controls. Prevotellaceae was more abundant in IBS patients than in control group (14.27% versus 6.13%, p?=?0.023), while Mycobacteriaceae (0.06% versus 0.17%, p?=?0.024) and Neisseriaceae (6.40% versus 8.94%, p?=?0.038) was less abundant in IBS patients’ jejunal mucosa than those in controls. This less abundant jejunal Neisseriaceae was associated with more severe IBS (p?=?0.03). The ratio of Firmicutes to Bacteroidetes in the stool of IBS-diarrhoea type patients was approximately three-fold higher, and the ratio of Firmicutes to Actinobacter in SI of IBS-mixed type patients was about nine-fold higher than healthy subjects. Conclusion Higher abundance of colonic Veillonellaceae and SI Prevotellaceae, and lower amount of oral cavity normal flora in proximal SI were found in IBS patients. We may manipulate these bacteria in IBS patients in future studies (ClinicalTrial.gov Number NCT01679730).     

Effect of Lactobacillus plantarum 299v on colonic fermentation and symptoms of irritable bowel syndrome

A number of recent clinical trials have promoted the use of probiotic bacteria as a treatment for irritable bowel syndrome (IBS). The recent demonstration of abnormal colonic fermentation in some patients with this condition provides an opportunity for the objective assessment of the therapeutic value of these bacteria. This study was designed to investigate the effects of Lactobacillus plantarum 299V on colonic fermentation. We conducted a double-blind, placebo-controlled, cross-over, four-week trial of Lactobacillus plantarum 299V in 12 previously untreated patients with IBS. Symptoms were assessed daily by a validated composite score and fermentation by 24-hr indirect calorimetry in a 1.4-m³ canopy followed by breath hydrogen determination for 3 hr after 20 ml of lactulose. On placebo, the median symptom score was 8.5 [6.25–11.25 interquartile range (IQR)], the median maximum rate of gas production was 0.55 ml/min (0.4–1.1 IQR), and the median hydrogen production was 189.7 ml/24 hr (118.3–291.1 IQR). On Lactobacillus plantarum 299V the median symptom score was 8 (6.75–13.5 IQR), the median maximum rate of gas production 0.92 ml/min (0.45–1.5 IQR), and the median hydrogen production 208.2 ml/24 hr (146–350.9 IQR). There was no significant difference. Breath hydrogen excretion after lactulose was reduced by the probiotic (median at 120 min, 6 ppm; placebo, 17 ppm; P = 0.019). In conclusion, Lactobacillus plantarum 299V in this study did not appear to alter colonic fermentation or improve symptoms in patients with the irritable bowel syndrome.     

A prospective assessment of bowel habit in irritable bowel syndrome in women: defining an alternator

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is subtyped as IBS with diarrhea (IBS-D) or IBS with constipation (IBS-C) based on Rome II guidelines. The remaining group is considered as having mixed IBS (IBS-M). There is no standard definition of an alternator (IBS-A), in which bowel habit changes over time. Our aim was to use Rome II criteria to prospectively assess change in bowel habit for more than 1 year to understand IBS-A. METHODS: Female patients (n=317) with IBS entering a National Institutes of Health treatment trial were studied at baseline with questionnaires and 2-week daily diary cards of pain and stool frequency and consistency. Studies were repeated at the end of treatment (3 months) and at four 3-month intervals for one more year. Algorithms to classify subjects into IBS-D, IBS-C, and IBS-M groups used diary card information and modified Rome II definitions. Changes in bowel habit at 3-month intervals were then assessed using these surrogate diary card measures. RESULTS: At baseline, 36% had IBS-D, 31% IBS-M, and 34% IBS-C. Except for stool frequency, there were no differences between groups. While the proportion of subjects in each subgroup remained the same over the year, most individuals (more than 75%) changed to either of the other 2 subtypes at least once. IBS-M was the least stable (50% changed out by 12 weeks). Patients were more likely to transition between IBS-M and IBS-C than between IBS-D and IBS-M. Notably, only 29% switched between the IBS-D and IBS-C subtypes over the year. CONCLUSIONS: While the proportion of subjects in each of the IBS subtypes stays the same, individuals commonly transition between subtypes, particularly between IBS-M and IBS-C. We recommend that IBS-A be defined as at least one change between IBS-D and IBS-C by Rome II criteria over a 1-year period.     

The epidemiology of irritable bowel syndrome in a random population: prevalence,incidence, natural history and risk factors

Abstract. Objectives . The aim of the study was to assess prevalence, incidence, recovery, and risk factors of irritable bowel syndrome according to different definitions in a large random population. Design . A 5 year follow-up study of a sex- and age-stratified random sample of 4581 Danes interviewed about abdominal symptoms. Setting . The Glostrup Populations Studies Unit at Glostrup County Hospital. Main outcome measures . Prevalence, incidence, recovery, and the association of risk factors to irritable bowel syndrome (IBS). The percentage of subjects common to the populations selected by the various definitions of IBS. Results . According to various definitions, the prevalence of IBS varied from 5 to 65% and the incidence varied from 1 to 36%. At the 5 year follow-up only 5% of subjects with IBS were completely free of all symptoms. Psychological vulnerability and the experience of having problems were strongly associated with prevalence and incidence of IBS, whereas lifestyle factors only showed a very weak or no relationship to IBS. Populations defined as suffering from IBS according to the various definitions had less than 50% of the subjects in common. Conclusions . Irritable bowel syndrome is frequent but fluctuating in the general population. Psychological factors seem to be of greater aetiological importance to IBS than lifestyle factors. However, a generally accepted and precise definition is essential to make future studies comparable and to allow general conclusions to be drawn. Furthermore, it still needs to be verified whether the syndrome is a disease entity or just an acceptable, common life-condition.     

Fermentable oligosaccharides,disaccharides, monosaccharides and polyols: role in irritable bowel syndrome

Irritable bowel syndrome (IBS) was previously left poorly treated despite its high prevalence and cost. Over the past decade, significant research has been conducted providing new dietary strategies for IBS management. The ‘low fermentable oligosaccharides, disaccharides, monosaccharides and polyols diet’ has shown symptom improvement in 68–76% of patients. Randomized, controlled trials have now proven its efficacy. The diet, low in poorly absorbed and fermentable carbohydrates, uses dietary restriction and re-challenge to determine individual tolerance to various short-chain carbohydrates. However there may be potential detrimental effects of the diet in the long term, due to potential changes to the gastrointestinal microbiota. Appropriate dietary education and management of the diet is imperative. Future research should focus on the relevance of changes to the microbiota and ways to liberalize the dietary restrictions.     

Guidelines on the irritable bowel syndrome: mechanisms and practical management

Background

IBS affects 5–11% of the population of most countries. Prevalence peaks in the third and fourth decades, with a female predominance.

Aim

To provide a guide for the assessment and management of adult patients with irritable bowel syndrome.

Methods

Members of the Clinical Services Committee of The British Society of Gastroenterology were allocated particular areas to produce review documents. Literature searching included systematic searches using electronic databases such as Pubmed, EMBASE, MEDLINE, Web of Science, and Cochrane databases and extensive personal reference databases.

Results

Patients can usefully be classified by predominant bowel habit. Few investigations are needed except when diarrhoea is a prominent feature. Alarm features may warrant further investigation. Adverse psychological features and somatisation are often present. Ascertaining the patients'' concerns and explaining symptoms in simple terms improves outcome. IBS is a heterogeneous condition with a range of treatments, each of which benefits a small proportion of patients. Treatment of associated anxiety and depression often improves bowel and other symptoms. Randomised placebo controlled trials show benefit as follows: cognitive behavioural therapy and psychodynamic interpersonal therapy improve coping; hypnotherapy benefits global symptoms in otherwise refractory patients; antispasmodics and tricyclic antidepressants improve pain; ispaghula improves pain and bowel habit; 5‐HT₃ antagonists improve global symptoms, diarrhoea, and pain but may rarely cause unexplained colitis; 5‐HT₄ agonists improve global symptoms, constipation, and bloating; selective serotonin reuptake inhibitors improve global symptoms.

Conclusions

Better ways of identifying which patients will respond to specific treatments are urgently needed.     

复方枸橼酸阿尔维林合用四磨汤治疗腹泻型肠易激综合征的疗效评价

目的 为观察复方枸橼酸阿尔维林合用四磨汤治疗肠易激综合征的近期疗效。方法 采用随机对照方法，将90例IBS病人随机分为治疗组（45例）和对照组（45例），15天观察疗效。结果 治疗组的显效率和总有效率分别为57.8％和96.6％，对照组则分别为26．7％和66．6％，差异非常显著性。结论 复方枸橼酸阿尔维林合用四磨汤可以有效缓解腹泻型IBS病人的临床症状，近期疗效明显。     

Rifaximin for the treatment of diarrhea-predominant irritable bowel syndrome

Irritable bowel syndrome (IBS) is a chronic, functional bowel disorder characterized by abdominal pain or discomfort and altered bowel habit. The pathophysiology is unclear, but may include altered gut motility, visceral hypersensitivity, abnormal central pain processing, chronic low-grade intestinal inflammation, or disturbances in the gut microbiome. These etiological mechanisms, alongside environmental factors such as stress and anxiety, vary between individuals and represent potential targets for treatment. Rifaximin is a poorly absorbed oral antibiotic proposed to act on the gut microenvironment, used in the treatment of travelers’ diarrhea and hepatic encephalopathy. Clinical trials suggest the drug can reduce global IBS symptoms and improve bloating, abdominal pain, and stool consistency in some patients with non-constipated IBS, leading to Food and Drug Administration approval in the United States. This article considers the pharmacology of rifaximin, the evidence for its use in IBS, and the safety and tolerability of the drug.     

Effect of a calcium channel blocker and antispasmodic in diarrhoea-predominant irritable bowel syndrome

BACKGROUND: Irritable bowel syndrome (IBS) is a colonic function disorder. Both pinaverlum bromide (a selective calcium channel blocker) and mebeverine (an antispasmodic) are reported to be effective in the long-term (12-16 weeks) treatment of IBS patients. Their efficacy in the short-term treatment of IBS patients and colonic transit time is unclear. Furthermore, substance P and neuropeptide Y have either excitatory or inhibitory effects on colonic motility. Whether the efficacy of both drugs is mediated through these neuropeptides remains unknown. METHODS AND RESULTS: A clinical trial was conducted with 91 patients with diarrhoea-predominant IBS. After basal measurement of the total colonic transit time, IBS patients were randomized to receive either pinaverlum bromide (50 mg, t.i.d.) or mebeverine (100 mg, t.i.d.) for 2 weeks. The symptomatic scores regarding defaecation, total colonic transit time and serum levels of substance P and neuropeptide Y were measured before and after treatments. The daily defaecation frequency was markedly decreased after treatment (pinaverlum bromide, 2.9+/-1.2 vs 2.0+/-1.0, P< 0.05; mebeverine, 2.7+/-1.1 vs 2.1+/-1.0, P< 0.05). The stool consistency became well formed after both treatments (P< 0.05). Both drugs similarly improved the global well-being in these IBS patients (pinaverlum bromide vs mebeverine 73.4 vs 71.8%, P> 0.05). The total colonic transit time was significantly prolonged only after pinaverlum bromide treatment (21.4+/-15.5 vs 30.8+/-14.8 h, P< 0.01). Neither substance P nor neuropeptide Y serum level was significantly changed after either treatments. CONCLUSION: Pinaverlum bromide and mebeverine have similar therapeutic efficacies on diarrhoea-predominant IBS patients. Prolonged colonic transit time may be one of the factors responsible for the efficacy of pinaverlum bromide on the IBS patients. Substance P and neuropeptideY appear less important in the pathogenesis of diarrhoea-predominant IBS.     

Gender-related differences in visceral perception in health and irritable bowel syndrome

BACKGROUND: Irritable bowel syndrome (IBS) is more common in female subjects, and IBS patients generally exhibit reduced pain thresholds to rectal distension. The aim of the present paper was to determine gender-related differences in rectal perception in both healthy controls and IBS patients. METHODS: Fifty-nine IBS patients (age 20-65 years; mean, 39.2 years; 31 women, 28 men) with symptoms that fulfilled Rome-II criteria and 21 healthy controls (age 25-58 years; mean, 37.8 years; 11 women, 10 men) were recruited. Participants completed a questionnaire regarding bowel symptoms and psychological distress, and maximal tolerable pressures were evaluated via barostat tests. RESULTS: Although healthy women appear to have lower perception thresholds than men, significant gender differences in pain sensitivity were not detected (P > 0.05). In addition, female patients with IBS also exhibited no enhanced colorectal perception, as compared with male IBS patients (P > 0.05). CONCLUSIONS: No gender differences in visceral perception were determined to exist between the healthy controls and the IBS patients. Therefore, the increased prevalence of IBS in women may be related to another set of pathophysiological factors, and not to gender-related differences in visceroperception.     

肠易激综合征的治疗进展

肠易激综合征（irritable bowel syndrome,IBS）作为消化系统疾病中较为常见的功能性胃肠病,由于发病机制未 明,临床上缺乏行之有效的治疗手段,其临床诊治一直以来是研究的热点和难点。而近年来,相关药物的研发及诊疗 策略的更新,使得IBS的诊疗得到了进一步发展。文章就目前IBS的治疗进展做一论述,以期为IBS的临床诊治提供 指导,使更多的IBS患者从中获益。     

Visceral perception in irritable bowel syndrome

We wished to determine if visceral perception in the rectum and stomach is altered in patients with irritable bowel syndrome and to evaluate the effects on visceral sensation of 5-HT₃ receptor blockade. Twelve community patients with diarrhea-predominant irritable bowel syndrome and 10 healthy controls were studied in a double-blind, randomized, placebo-controlled study. Using two barostats, the stomach and rectum were distended, with pressure increments of 4 mm Hg, from 10 to 26 mm Hg; visceral perception was measured on an ordinal scale of 0–10. Personality traits were measured using standard psychological methods, and somatic pain was evaluated by immersion of the nondominant hand in cold water. The effect of 5-HT₃ antagonism was tested with a single intravenous dose of ondansetron at 0.15 mg/kg. Gastric perception was higher in irritable bowel syndrome, but rectal distension was perceived similarly in irritable bowel syndrome and controls. Pain tolerance to cold water was also similar in irritable bowel syndrome and controls. Ondansetron induced rectal relaxation and increased rectal compliance but did not significantly alter gastric compliance or visceral perception. Psychological test scores were similar in patients and controls. We conclude that in this group of psychologically normal patients with irritable bowel syndrome, who were not chronic health-care seekers, visceral perception was normal. Ondansetron did not alter gut perception in health or in irritable bowel syndrome.This work was supported in part by grants AG09440, DK32121, and RR585 from the National Institutes of Health.     

Systematic review with meta-analyses: does the pathogen matter in post-infectious irritable bowel syndrome?

Objective: Acute gastroenteritis (AGE) is a risk factor for post-infectious irritable bowel syndrome (PI-IBS). This systematic review evaluates the prevalence and risk-factors of PI-IBS after AGE by specific pathogens.

Materials and methods: Medline (1966–2019) and Embase (1974–2019) were searched for studies evaluating PI-IBS minimum 3 months after AGE with Campylobacter spp., Salmonella spp., Shigella spp., Escherischia coli, Clostridium difficile, norovirus, rotavirus, Cryptosporidium spp. or Giardia intestinalis using validated criteria for IBS. Pooled prevalence (PP), odds ratios (OR) and risk factors were determined for single pathogens, groups of bacteria, viruses and parasites, and overall for AGE caused by any pathogen. Random-effect models were used for meta-analyses.

Results: A total of 34 articles were included. PP of PI-IBS after Campylobacter spp. was 12% (confidence interval 95% [CI]: 10–15%), Salmonellosis 12% (CI: 9–15%), Shigellosis 11% (CI: 8–15%), C. difficile 14% (CI: 4–29%) and E. coli spp. 12% (CI: 5–20%). OR of PI-IBS after salmonellosis was 5.5 (CI: 2.3–12.8) and after shigellosis 13.8 (CI: 4.2–45.4). Bacterial AGE overall showed OR 5.8 (CI: 4.0–8.3) and AGE caused by any pathogen OR 4.9 (CI: 3.9–6.1). Few studies exist on viral and parasitic gastroenteritis.

Conclusions: Current literature show similar risks for bacterial pathogens. Studies are limited for viral and parasitic pathogens. The evaluated risk-factors for PI-IBS varied among the included studies and the existing evidence is insufficient to identify pathogen-specific risk factors.     

Irritable bowel syndrome,the microbiota and the gut-brain axis

Irritable bowel syndrome is a common functional gastrointestinal disorder and it is now evident that irritable bowel syndrome is a multi-factorial complex of changes in microbiota and immunology. The bidirectional neurohumoral integrated communication between the microbiota and the autonomous nervous system is called the gut-brain-axis, which integrates brain and GI functions, such as gut motility, appetite and weight. The gut-brain-axis has a central function in the perpetuation of irritable bowel syndrome and the microbiota plays a critical role. The purpose of this article is to review recent research concerning the epidemiology of irritable bowel syndrome, influence of microbiota, probiota, gut-brain-axis, and possible treatment modalities on irritable bowel syndrome.