Microbial signatures in post-infectious irritable bowel syndrome – toward patient stratification for improved diagnostics and treatment

Irritable bowel syndrome (IBS) is a multifactorial and heterogeneous disorder estimated to affect over 10% of the Western population. A subset of the patients reports the start of the disease after an episode of gastroenteritis. The alterations in the intestinal microbiota of the post-infectious IBS (PI-IBS) patients were recently investigated in a British cohort and shown to differentiate from the healthy controls and resemble that of diarrhea-predominant IBS (IBS-D) patients. The altered 27 genus-like groups created a microbial signature, which could be used to objectively stratify patients and healthy controls. In this addendum, we combine the microbiota data derived from the British cohort with that of a recently reported Swedish PI-IBS cohort. Remarkably, robust and reproducible microbiota signatures were observed in these PI-IBS patients. We discuss these results with attention on the emerging role of microbiota in the classification, development and treatment of PI-IBS.     

When is irritable bowel syndrome not irritable bowel syndrome? Diagnosis and treatment of chronic functional abdominal pain

Functional abdominal pain syndrome (FAPS) is a distinct chronic gastrointestinal (GI) pain disorder characterized by the presence of constant or frequently recurring abdominal pain that is not associated with eating, change in bowel habits, or menstrual periods. The pain experience in FAPS is predominantly centrally driven as compared to other chronic painful GI conditions such as inflammatory bowel disease and chronic pancreatitis where peripherally acting factors play a major role in driving the pain. Psychosocial factors are often integrally associated with the disorder and can pose significant challenges to evaluation and treatment. Patients suffer from considerable loss of function, which can drive health care utilization. Treatment options are limited at best with most therapeutic regimens extrapolated from pain management of other functional GI disorders and chronic pain conditions. A comprehensive approach to management using a biopsychosocial construct and collaboration with pain specialists and psychiatry is most beneficial to the management of this disorder.     

Physicians’ attitudes and practices in the evaluation and treatment of irritable bowel syndrome

Objective. Irritable bowel syndrome (IBS) is a common disorder characterized by abdominal discomfort and disordered bowel habits. Despite the high prevalence of IBS, little is known about how physicians perceive this condition. The aims of our study were to measure physicians’ understanding of IBS, to assess their attitudes towards patients with IBS, and to determine whether there are differences in the way Internal Medicine physicians (IM), Family Practice physicians (FP), and Gastroenterology physicians (GI) evaluate and treat IBS patients. Material and methods. A survey was sent to 3000 physicians nationwide, 1000 each to IM, FP, and GI. The survey contained 35 questions assessing demographics, the etiology and pathophysiology of IBS, the use of diagnostic tests, and practice patterns and attitudes. Results. Of the deliverable questionnaires, 501 were returned completed; 472 of the respondents interviewed only adult patients, representing the cohort for this analysis. The mean age of all respondents was 47; most were men (80%). IM and FP made a new diagnosis of IBS 1.3–1.6 times each week, while GI made a new diagnosis 5.4 times each week (p<0.0001). Compared with the perceptions of FP and IM, GI felt that IBS patients were less sick than other patients (p<0.001), although they required more time per visit. More GI compared with FP and IM stated that prior infection and a history of abuse were the causes of IBS (p<0.01), while FP were more likely to believe that diet was a cause of IBS (p<0.01). GI felt a new diagnosis of IBS could be made without further testing 42% of the time. FP and IM felt that one-third of IBS patients needed referral to a GI. Conclusions. The attitudes and practice patterns of physicians towards patients with IBS differ depending on practice specialty. This may be due to differences in training, the ability to perform specialized tests, and/or differences in referral patterns. Further training may improve the ability of physicians in all specialties confidently to diagnose and treat patients with IBS.     

A role for inflammation in irritable bowel syndrome?

Attention has been directed to the putative role of low grade mucosal inflammation in irritable bowel syndrome (IBS) on the basis of evidence showing that some patients with IBS have an increased number of inflammatory cells in the colonic and ileal mucosa. Previous episodes of infectious enteritis, genetic factors, undiagnosed food allergies, and changes in bacterial microflora may all play a role in promoting and perpetuating this low grade inflammatory process. Human and animal studies support the concept that inflammation may perturb gastrointestinal reflexes and activate the visceral sensory system even when the inflammatory response is minimal and confined to the mucosa. Thus abnormal neuroimmune interactions may contribute to the altered gastrointestinal physiology and hypersensitivity that underlies IBS. A brief review of the human and animal studies that have focused on the putative role of intestinal inflammation and infections in the pathogenesis of IBS is given.     

Serotonin transporter gene polymorphisms in irritable bowel syndrome and their impact on tegaserod treatment

Objective To investigate the serotonin reuptake transporter (SERT) genetic polymorphisms in the 5 -hydroxytryptamine (5-HT) transporter gene-linked polymorphic region (5-HTTLPR) and the variable number tandem repeats (VNTRs) in intron 2 among Chinese people, and their relationship to the pathogenesis of irritable bowel syndrome (IBS);and to investigate the im-     

Inflammation in irritable bowel syndrome: Myth or new treatment target?

Low-grade intestinal inflammation plays a key role in the pathophysiology of irritable bowel syndrome(IBS), and this role is likely to be multifactorial. The aim of this review was to summarize the evidence on the spectrum of mucosal inflammation in IBS, highlighting the relationship of this inflammation to the pathophysiology of IBS and its connection to clinical practice. We carried out a bibliographic search in Medline and the Cochrane Library for the period of January 1966 to December 2014, focusing on publications describing an interaction between inflammation and IBS. Several evidences demonstrate microscopic and molecular abnormalities in IBS patients. Understanding the mechanisms underlying low-grade inflammation in IBS may help to design clinical trials to test the efficacy and safety of drugs that target this pathophysiologic mechanism.     

The gut–brain axis in irritable bowel syndrome and inflammatory bowel disease

Research increasingly demonstrates the bidirectional communication between gut microbiota and the brain, enhancing the role of gut microbiota modulation in the treatment of central nervous system (CNS) disorders. The first five years of life are extremely important as it affects the development of gut microbiota, immune system and, consequently, the onset of psychometric alterations, particularly in genetically predisposed individuals.In this review, we focus on the link between specific microbial genera, gastrointestinal (GI) disorders, anxiety and depression and on the effects of different therapeutic strategies for mood disorders on gut microbiota.     

Probiotics for irritable bowel syndrome: a light in the darkness?

Probiotics have been used with apparent success for several gut disorders, so it is not surprising they have been tried in the treatment of irritable bowel syndrome (IBS). However, the pathogenesis of this disease is unknown, and opinions about how probiotics might work are speculative. Nevertheless, two small trials suggest they might benefit patients with IBS, particularly those suffering from pain and bloating. This possibility deserves further study. It is important though, that future trials employ criteria-identified subjects, be sufficiently powered and strictly double blind, and select a suitable outcome measure. Until state-of-the-art trials of probiotics are available, their use should remain in the experimental arena.     

Effectiveness and safety of herbal medicines in the treatment of irritable bowel syndrome： A systematic review

AIM： To explore the efficacy and safety of herba medicines （HM） in the treatment of irritable bowe syndrome （IBS）. METHODS： A computer-based as well as manual literature search was performed. We reviewed randomized controlled trials on the treatment of IBS with and without HM. RESULTS： A total of 22 studies with 25 HMs met the inclusion criteria. Four of these studies were of good quality, while the remaining 18 studies involving 17 Chinese herbal medicine （CHM） formulas were of poor quality. Eight of these reports using 9 HMs showed global improvement of IBS symptoms, 4 studies with 3 HMs were efficacious in diarrhea-predominant IBS, and 2 studies with 2 HMs showed improvement in constipation- predominant IBS. Out of a total of 1279 patients, 15 adverse events in 47 subjects were reported with HM. No serious adverse events or abnormal laboratory tests were observed. The incidence of the adverse events was low （2.97%; 95% CI： 2.04%-3.90%）. CONCLUSION： Herbal medicines have therapeutic benefit in IBS, and adverse events are seldom reported in literature. Nevertheless, herbal medicines should be used with caution. It is necessary to conduct rigorous, well-designed clinical trials to evaluate their effectiveness and safety in the treatment of IBS.     

Double-blind placebo-controlled study of mesalamine in post-infective irritable bowel syndrome – a pilot study

Abstract

Objective. Post-infective irritable bowel syndrome (PI-IBS) is characterized by continuing symptoms of irritable bowel syndrome, typically diarrhea-predominant, following an episode of acute gastroenteritis. There is often an increase in sub-epithelial inflammatory and neuroendocrine cells on colonic mucosal biopsy. Mesalamine is an anti-inflammatory agent, effective in the treatment of inflammatory bowel disease. The goal of this study was to compare mesalamine to placebo on symptoms and quality-of-life (QOL) in PI-IBS. Material and methods. Twenty patients who developed diarrhea-predominant IBS after gastroenteritis were randomized to receive mesalamine (Asacol®) 1.6 gm b.i.d. or placebo for 12 weeks in a double-blind placebo-controlled study. QOL was assessed using the IBS-QOL questionnaire. Stool frequency, stool consistency, urgency, severity of abdominal pain, severity of bloating, and global-improvement scale were recorded in daily diaries for 7 days at baseline and every 4 weeks. Data were analyzed by comparing the change from baseline to last follow-up. Results. One patient withdrew after randomization; data were incomplete in two patients. Thus, data were analyzed from 17 patients (11 men and 6 women, median age: 27 years, range 22–45 years). Mesalamine was not associated with significant improvement in global symptoms, abdominal pain, bloating, stool urgency, frequency, or consistency (all p ≥ 0.11) or QOL (p ≥ 0.16). Conclusions. There was no significant improvement in global symptoms or overall QOL with mesalamine in patients with PI-IBS.     

Is lactose intolerance implicated in the development of post-infectious irritable bowel syndrome or functional diarrhoea in previously asymptomatic people?

OBJECTIVE: The relationship between lactose intolerance and post-infectious irritable bowel syndrome (IBS) in adults is uncertain. Bowel symptoms may persist after bacterial gastroenteritis and as post-infectious IBS. Acquired lactose intolerance may follow viral enteric infections in children. We compared the frequency of lactose intolerance after bacterial gastroenteritis in adults with and without symptoms of IBS or functional diarrhoea at 3-6-months' follow-up. DESIGN: A prospective cohort study was conducted. METHODS: All subjects with bacterial gastroenteritis confirmed by stool culture from the microbiology laboratory and without prior IBS or functional diarrhoea were eligible to participate. IBS and functional diarrhoea were diagnosed via self-completed Rome II modular questionnaires. Lactose intolerance was determined from a rise in breath hydrogen and plasma glucose and symptoms. RESULTS: One hundred and twenty-eight subjects with bacterial gastroenteritis were followed prospectively, from which a smaller cohort of 42 subjects took part in this study. The cohort was comprised of 24/25 subjects who developed post-infectious IBS (n = 16) or functional diarrhoea (n = 8) (9 male, 15 female) and 18 random controls (8 male, 10 female) chosen from the group without IBS or functional diarrhoea. The mean age of the subjects was 44.4 years (range 25-76 years). In the group with functional diarrhoea or IBS, four subjects had failure of the plasma glucose to rise but none had abnormal glucose hydrogen breath tests. In the control subjects, one had a positive combined test and six had failure of plasma glucose to rise alone. No subject developed symptoms during the test. CONCLUSIONS: Bacterial gastroenteritis did not cause persistent lactose intolerance in our study population. Lactose intolerance does not appear to be implicated in the aetiology of post-infectious bowel symptoms, including IBS. Advice to avoid dairy products in patients presenting with post-infectious IBS on the basis that they may have lactose intolerance appears unnecessary in patients from northern England.