Alterations in gut microbiota are postulated to be an etiologic factor in the pathogenesis of irritable bowel syndrome (IBS). To determine whether IBS patients in China exhibited differences in their gut microbial composition, fecal samples were collected from diarrhea-predominant IBS (IBS-D) and healthy controls and evaluated by 16S ribosomal RNA gene sequence and quantitative real-time PCR. A mouse model of postinfectious IBS (PI-IBS) was established to determine whether the altered gut microbiota was associated with increased visceral hypersensitivity. The results indicated that there were significant differences in the bacterial community profiles between IBS-D patients and healthy controls. Prevotella was more abundant in fecal samples from IBS-D patients compared with healthy controls (p < 0.05). Meanwhile, there were significant reductions in the quantity of Bacteroides, Bifidobacteria, and Lactobacillus in IBS-D patients compared with healthy controls (p < 0.05). Animal models similarly showed an increased abundance of Prevotella in fecal samples compared with control mice (p < 0.05). Finally, after the PI-IBS mice were cohoused with control mice, both the relative abundance of Prevotella and visceral hypersensitivity of PI-IBS mice were decreased. In conclusion, the altered intestinal microbiota is associated with increased visceral hypersensitivity and enterotype enriched with Prevotella may be positively associated with high risk of IBS-D.

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Inflammatory cytokines produced by activated macrophages largely contribute to the pathological signs of inflammatory bowel disease (IBD). Interleukin-10 (IL-10) is the predominant anti-inflammatory cytokine in the intestine, and its therapeutic efficacy for IBD has been clinically tested. Nevertheless, how the function of IL-10 is regulated in the intestinal microenvironment remains unknown, which largely hinders the further development of IL-10–based therapeutic strategies. Here, we found that the expression of phosphatase Shp2 was increased in colonic macrophages and blood monocytes from IBD patients compared with those from healthy controls. Shp2 deficiency in macrophages protects mice from colitis and colitis-driven colon cancer. Mechanistically, Shp2 disrupts IL-10–STAT3 signaling and its dependent anti-inflammatory response in human and mouse macrophages. Furthermore, a Shp2-inducing role of TNF-α is unveiled in our study. Collectively, our work identifies Shp2 as a detrimental factor for intestinal immune homeostasis and hopefully will be helpful in the future exploitation of IL-10 immunotherapy for IBD.