Bugs and Irritable Bowel Syndrome: The Good, the Bad and the Ugly

Uday C Ghoshal; Hyojin Park; Kok-Ann Gwee


J Gastroenterol Hepatol. 2010;25(2):244-251. 

In This Article

How could Normal or Abnormal Gut Flora Affect GI Sensorimotor Functions?

Gut flora could affect the sensorimotor functions of the gut in three ways: (i) end products of bacterial fermentation and metabolism; (ii) neuroendocrine factors; and (iii) immune mediators.

Bacterial chemotactic peptides, such as formyl–methionyl–leucyl–phenylalanine, stimulate the enteric nervous system and afferent nerves, while endotoxin (lipopolysaccharide) may affect gut motility.[3] Short-chain fatty acids (SCFA), such as butyrate, acetate, and propionate have important roles in gut health and motility and may contribute to pathogenesis of gastrointestinal diseases.[83,84] SCFA are important nutrients to maintain healthy colonocytes.[83] They stimulate absorption of water and electrolytes and thereby prevent diarrhea.[83] Colonic acidification by SCFA may increase its motility.[85] In contrast, motility of proximal gut by SCFA is reduced due to induction of the ileal brake;[84] as a result, reduced proximal gut motility may predispose to SIBO. Bacteria in the small intestine in patients with SIBO produce SCFA and deconjugate bile acids.[86] These may contribute to diarrhea in patients with SIBO.

Bacterial fermentation and production of various gases may contribute to the pathogenesis IBS and its symptoms. A study by Pimentel et al. from the USA reported that 12 (39%) of 31 constipation-predominant IBS patients excreted methane, whereas none of 34 diarrhea-predominant patients were methane excreters.[87] This led to a hypothesis that methane gas produced by bacteria may contribute to the development of constipation in patients with IBS.[88] In dogs, luminal methane infusion compared with room air infusion significantly reduced intestinal transit.[17] Exposing tissues to methane also increased the force of contractions in response to mucosal stimulation; the authors therefore suggested that methane predisposes to constipation via promotion of segmental, non-propagating contractions.[17]

In a study in guinea pigs, the amplitude of peristaltic contraction was significantly decreased when hydrogen was infused, whereas it was significantly increased in the methane infusion group.[89] Further, peristaltic velocity was significantly delayed after methane infusion.[89] The area under curve of intra-luminal pressure was also markedly increased after infusion of methane. These results support the concept that methane promotes non-propagating or segmental contractions of the small bowel. This study provides an experimental basis for verifying that there is a significant correlation between methane producers and constipation-predominant IBS.[89] Some authors have hypothesized that methanogenic flora may reduce flatulence; as one molecule of carbon dioxide combines with four molecules of hydrogen to produce one molecule of methane, it may result in reduction of total volume of gas in the gut.[58] In an Indian study, predominant methanogenic flora (fasting methane concentration > 10 ppm) was present in 50/345 (14.5%) patients with IBS diagnosed by Rome II criteria as compared with 88/254 (34.6%) of healthy controls.[58] These studies suggest that the gut flora and the gas produced by it may play a role in the pathogenesis of IBS symptoms, but more studies are needed to resolve this issue.

Neuroendocrine factors are important mechanisms of control of sensorimotor functions by the gut flora. Ileal brake is a physiological phenomenon, in which the presence of fat or products of its digestion such as fatty acids reduces motility of proximal small intestine. Colonic flora produces SCFA, reflux of which into the ileum liberates peptide YY, neurotensin and glucagon-like peptide-1 that inhibits proximal gut motility (ileal brake).[90] SCFA produced by gut flora influences serotonin, motilin and somatostatin containing enteroendocrine cells in the colon and ileum;[91] these are key mediators of gut motility.

Gut flora is also important in normal development of the intestinal immune system and lymphoid tissue.[3] The gut immune system, which includes the cytokine profile, determines the degree and duration of inflammation in response to microbial challenge of the intestine.[92] Since gut inflammation is an important determinant of its sensorimotor functions and development of functional bowel disease, the importance of the immune system in regulating gut sensorimotor function cannot be underestimated.[92]

A study in an animal model illustrated the role of inflammation induced by infection on gut motility, which could have a bearing on development of functional bowel disorders complicating to infection.[93] Authors developed an animal model of persistent gut hypercontractility following acute gastrointestinal infection and studied the mechanisms of persistent hypercontractility. NIH Swiss mice were infected with Trichinella spiralis. Jejunal longitudinal muscles from these mice were incubated with or without cytokines. Subsequently, muscle contraction and cytokine mRNA and cytokine expression were examined.[93] During acute infection, IL-4 or IL-13, transforming growth factor (TGF)-β1, and cyclooxygenase (COX)-2 expressions were increased in intestinal smooth muscle. Following infection, Th2 cytokine expression returned to normal, but TGF-β1 expression remained high in the muscle layer. Exposure of muscle cells to IL-4 or IL-13 increased TGF-β1, COX-2 protein, and prostaglandin (PG)E2. Exposure of muscle cells to TGF-β1 increased PGE2 and COX-2 protein. Incubation of tissue with IL-4, IL-13, TGF-β1, or PGE2 increased carbachol-induced muscle contractility. COX-2 inhibitor attenuated TGF-β1-induced hypercontractility of the muscles. The authors suggested that Th2 cytokines induce muscle hypercontractility during infection by a direct action on smooth muscle. The maintenance of hypercontractility results from Th2 cytokine-induced expression of TGF-β1 and the subsequent upregulation of COX-2 and PGE 2 at the level of the smooth muscle cell.


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