Effect of altered gut microbiota on visceral hypersensitivity of postinfectious irritable bowel syndrome mice.

Abstract

Irritable bowel syndrome (IBS) is a common functional bowel disorder characterized with visceral hypersensitivity. Previous studies indicated gut microbiota alteration associated short-chain fatty acids (SCFAs) dysregulation is associated with IBS development. The aim of the study is to explore the potential role of microbiota dysbiosis mediated visceral hypersensitivity in postinfectious-IBS (PI-IBS) mouse model. Four-week-old NIH mice were randomly allocated into four groups: control mice, PI-IBS mice, PI-IBS mice co-housing with normal mice, and PI-IBS mice were administrated with a cocktail of antibiotics. Trichinella spiralis infection established PI-IBS mouse model. Microbiota in cecal contents and feces were analyzed by 16S rDNA sequencing. SCFAs were detected by gas chromatography. 5-hydroxytryptamine (5-HT) was evaluated by ELISA, and N-methyl-D-aspartate receptors (NMDARs) were examined by western blot. Visceral sensitivity was determined by abdominal withdrawal reflex in response to colorectal distention. Increased SCFAs were observed in cecal contents and feces in PI-IBS mice accompanied with higher 5-HT and NMDAR subunits expressions in ileum and colon. Visceral hypersensitivity was observed in PI-IBS mice compared to control mice. When administrated with antibiotics cocktails and co-housing with normal mice, PI-IBS mice showed decreased SCFAs, 5-HT, NMDAR subunits expressions, and improved visceral hypersensitivity. Gut microbiota alteration induced increased SCFAs, 5-HT and NMDAR subunits expressions were associated with visceral hypersensitivity in PI-IBS mice. The critical role of gut microbiota in improving visceral hypersensitivity was further identified by treatment of antibiotics cocktail and co-housing.