Immune Activation and Gut Microbes in Irritable Bowel Syndrome

Abstract

Irritable bowel syndrome (IBS) is a highly prevalent disorder that is characterized by chronic abdominal pain and altered bowel habit. The diagnosis of IBS has traditionally been made by matching the complaints of the patient with established clinical criteria, since the underlying pathophysiology was not known. Various new findings have recently been reported in IBS patients that challenge our concept of IBS as a syndrome with no explanation. While the florid inflammation characteristic of inflammatory bowel disease is absent in IBS, changes suggesting immune activation are present in nearly all IBS patients. Is IBS an autoimmune disease, or is the immune activation responding to a trigger? In this review we present evidence that points to a state of immune activation in IBS and show data that suggest that small intestinal bacterial overgrowth triggers immune activation in IBS. (Gut and Liver 2009;3:14-19)

Revisiting concepts of visceral nociception in irritable bowel syndrome

“…Intestinal infection, on the other hand, can also cause alterations in gut microbiota by a loss of containment of the indigenous colonic microbial community or small intestinal bacterial overgrowth, which can also contribute to visceral afferent sensitization in IBS (Al‐Khatib and Lin, ), possibly also through interference with the intestinal barrier function (Rescigno, ). Further studies are needed to establish the role of these peripheral processes and to which extent they can contribute to alterations in pain perception in IBS.…”

Changes in Enteric Neurons of Small Intestine in a Rat Model of Irritable Bowel Syndrome with Diarrhea

“…The etiology of IBS is complex and appears to be multi-factorial, including altered gastrointestinal (GI) motility, visceral hypersensitivity, heredity, inflammation, and psycho-social factors. 1,2 Nevertheless, the etiology of IBS remains unknown.…”

Experimental endotoxemia as a model to study neuroimmune mechanisms in human visceral pain

“…Indicators of immune activation have also been documented in IBS patients without the onset of an acute infection, including alterations in mucosal cytokine production, mast cell activation, increased numbers of enterochromaffin cells and intraepithelial lymphocytes, low‐grade infiltration of T cells in the myenteric plexus with neuronal degeneration, increased fecal concentrations of the antimicrobial peptide beta‐defensin‐2, and increased capsaicin receptor TRPV1‐expressing sensory fibers in rectal biopsies, along with data suggesting a genetic predisposition favoring an increased production of tumor necrosis factor (TNF)‐α (reviewed in Refs. 9 and 21). The putative role of gut microbiota in disturbances of the brain–gut axis in IBS patients is increasingly recognized, and dysbiosis may play a critical role in immune activation and low‐grade inflammation in a proportion of patients 22 …”

“…Local inflammation of the intestine may indeed result in systemic immune activation, 12,15,23,24 likely mediated by an increased permeability of the intestinal mucosa 24 . Studies in IBS patients without a history of an infection revealed low‐grade activation of the innate immune system, including systemic increases in inflammatory markers such as TNF‐α, interleukin (IL)‐1β, IL‐6, and IL‐8 9,21 . Importantly, levels of proinflammatory cytokines, analyzed in the serum of IBS patients, have been found to be associated with IBS symptom score 25 .…”