Pimentel M¹, Lembo A². Dig Dis Sci. 2020 Feb 5. doi: 10.1007/s10620-020-06109-5. [Epub ahead of print]

Author information

1 Medically Associated Science and Technology (MAST) Program, Cedars-Sinai Medical Center, Los Angeles, CA, USA. pimentelm@cshs.org.

2 Division of Gastroenterology, Beth Israel Deaconess Hospital, Boston, MA, USA.

Abstract

Irritable bowel syndrome (IBS) is an extremely common and often very debilitating chronic functional gastrointestinal disorder. Despite its prevalence, significant associated healthcare costs, and quality-of-life issues for affected individuals, our understanding of its etiology remained limited. However, it is now evident that microbial factors play key roles in IBS pathophysiology. Acute gastroenteritis following exposure to pathogens can precipitate the development of IBS, and studies have demonstrated changes in the gut microbiome in IBS patients. These changes may explain some of the symptoms of IBS, including visceral hypersensitivity, as gut microbes exert effects on the host immune system and gut barrier function, as well as the brain-gut axis. Microbial differences also appear to underlie the two main functional categories of IBS: diarrhea-predominant IBS (IBS-D) is associated with small intestinal bacterial overgrowth, which can be diagnosed by a positive hydrogen breath test, and constipation-predominant IBS (IBS-C) is associated with increased levels of methanogenic archaea, which can be diagnosed by a positive methane breath test. Mechanistically, the pathogens that cause gastroenteritis and trigger subsequent IBS development produce a common toxin, cytolethal distending toxin B (CdtB), and antibodies raised against CdtB cross-react with the cytoskeletal protein vinculin and impair gut motility, facilitating bacterial overgrowth. In contrast, methane gas slows intestinal contractility, which may facilitate the development of constipation. While antibiotics and dietary manipulations have been used to relieve IBS symptoms, with varying success, elucidating the specific mechanisms by which gut microbes exert their effects on the host may allow the development of targeted treatments that may successfully treat the underlying causes of IBS.