Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome

Abstract

Ringel Y, Maharshak N.Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol 305: G529-G541, 2013. First published July 25, 2013; doi:10.1152/ajpgi.00207.2012.-The pathophysiology of irritable bowel syndrome (IBS) is believed to involve alterations in the brain-gut axis; however, the etiological triggers and mechanisms by which these changes lead to symptoms of IBS remain poorly understood. Although IBS is often considered a condition without an identified "organic" etiology, emerging evidence suggests that alterations in the gastrointestinal microbiota and altered immune function may play a role in the pathogenesis of the disorder. These recent data suggest a plausible model in which changes in the intestinal microbiota and activation of the enteric immune system may impinge upon the brain-gut axis, causing the alterations in gastrointestinal function and the clinical symptoms observed in patients with IBS. This review summarizes the current evidence for altered intestinal microbiota and immune function in IBS. It discusses the potential etiological role of these factors, suggests an updated conceptual model for the pathogenesis of the disorder, and identifies areas for future research.inflammation; gastrointestinal; microbiota IRRITABLE BOWEL SYNDROME (IBS) is the most common and best studied condition of a larger group of functional gastrointestinal (GI) disorders. Functional GI disorders refer to the presence of a variable combination of chronic or recurrent GI symptoms not explained by structural or biochemical abnormalities (130,159). IBS is characterized by chronic or recurring abdominal pain or discomfort that is associated with altered bowel habits (53, 99). The condition is often associated with other GI symptoms (e.g., bloating, distention, and gas), other functional GI disorders (e.g., functional dyspepsia), other non-GI disorders (e.g., fibromyalgia, interstitial cystitis, migraine headache), and psychological disorders (e.g., depression, anxiety, somatization) (96,146,167). Traditionally, IBS has been subtyped on the basis of the patient's predominant symptom/stool pattern (99). These subtypes include diarrhea predominant (IBS-D), constipation predominant (IBS-C), and mixed type (IBS-M), in which patients experience alternating periods of diarrhea and constipation. Unlike other conditions that can be associated with abdominal pain and abnormal bowel patterns such as inflammatory bowel diseases (IBD), IBS is not associated with any overt histopathology, structural, or biochemical abnormalities. IBS has been generally considered to be caused by alterations in the brain-gut axis (the bidirectional communication network involving the enteric nervous system, the autonomic nervous system, and the central nervous system) (60,108,125), and the pathophysiological mechanisms behind this condition remain unclear. Traditionally, IBS is considered to be a multifactorial condition in which multiple environmental, genetic, physiological, ...

Gut/brain axis and the microbiota

“…However, there is considerable controversy over the magnitude as well as the sites, pathways, and molecular mechanisms within the gut/brain axis that are responsible for these alterations. The intestinal microbiota and its metabolites have been shown to be involved in modulating GI functions, given their ability to affect intestinal permeability (8)(9)(10)(11), mucosal immune function (9)(10)(11)(12)(13)(14), intestinal motility (15) and sensitivity (14,16), and activity in the enteric nervous system (ENS) (reviewed in ref. 17).…”

Alteration of Fecal Microbiota in Patients With Postinfectious Irritable Bowel Syndrome (Gut 2014;63:1737-1745)

“…[1][2][3] Despite its high prevalence, the pathogenesis of IBS is still very little understood, and seems to be multi-factorial disease. [1][2][3] Many factors have been proposed to contribute to the pathogenesis of IBS, including visceral hypersensitivity, gastrointestinal dysmotility, activation of mucosal immune system, alterations of the gut microbiota, and impaired intestinal barrier function, as well as psychosocial distress. [1][2][3] Recently, a newly identified cause for IBS is infectious gastroenteritis.…”

“…[1][2][3] Many factors have been proposed to contribute to the pathogenesis of IBS, including visceral hypersensitivity, gastrointestinal dysmotility, activation of mucosal immune system, alterations of the gut microbiota, and impaired intestinal barrier function, as well as psychosocial distress. [1][2][3] Recently, a newly identified cause for IBS is infectious gastroenteritis. [1][2][3] About 10% of patients with IBS develop the symptoms consistent with diarrhea-predominant IBS (IBS-D) after an episode of infectious gastroenteritis and these patients are designated as postinfectious IBS (PI-IBS).…”

“…[1][2][3] Recently, a newly identified cause for IBS is infectious gastroenteritis. [1][2][3] About 10% of patients with IBS develop the symptoms consistent with diarrhea-predominant IBS (IBS-D) after an episode of infectious gastroenteritis and these patients are designated as postinfectious IBS (PI-IBS). …”

“…[1][2][3] Until now, there has been increasing interest in trying to identify potential mechanisms in IBS because of its heterogeneity in symptoms and clinical phenotypes, and this endeavor has been driven by recent evidence that gut microbiota composition is altered in IBS patients compared to HC and this alteration influences the clinical phenotypes and host immune response in IBS patients. 8,9 PI-IBS is a functional gastrointestinal disorder which begins after an acute episode of infectious gastroenteritis.…”