The intestinal mucosal barrier, which is composed of epithelial cells and mucus layers secreted by goblet cells and contains commensal bacteria, constitutes the first line of defense against pathogenic gut microbiota. However, homeostasis between the microbiota and mucus layer is easily disrupted by certain factors, resulting in alteration of the gut microbiota and entry of pathogens to the intestinal mucosal barrier. In this review, we describe the structures and functions of the mucus layer, expound several crucial influencing factors, including diet styles, medications and host genetics, and discuss how pathogenic microorganisms interact with the mucus layer and commensal microbiota, with the understanding that unraveling their complex interactions under homeostatic and dysbiosis conditions in the colon would help reveal some underlying pathogenic mechanisms and thus develop new strategies to prevent pathogenic microbiological colonization.

Fecal microbiota transplantation (FMT) induces remission in ulcerative colitis (UC). However, the treatment effect of FMT diminishes over time. Maintaining the diversity of the gut flora for long periods may improve the effects of FMT in UC. Pectin, which can be fermented by gut microbiota into short-chain fatty acids, is postulated to shape the composition and maintain the balance of gut microbiota following transplantation. This study investigated whether pectin could enhance the effects of FMT in UC patients. Three FMT patients and four FMTP patients achieved the primary outcome. The Mayo scores of the FMTP group were lower than those of the FMT group at weeks 4 and 12 (P = 0.042 and P = 0.042, respectively). There were no differences in the diversity of the gut flora between the two groups at weeks 4 and 12; however, the composition of the gut flora of the FMTP group was more similar than the FMT group to that of the donor at all-time points post-treatment. Pectin decreased the Mayo score by preserving the diversity of the gut flora following FMT for UC. Current Controlled Trial NCT02016469 . Registered 10 November 2013

High levels of immunoglobulin A (IgA)-coated bacteria may have a role in driving inflammatory bowel disease (IBD). We therefore investigated the effect of sodium butyrate on microbiota in IBD prone interleukin (IL)-10^−/− mice. At 8 weeks of age, mice were allocated into three groups (n = 4/group): normal (C57BL/6), IL-10^−/−, and IL-10^−/− treated with sodium butyrate (100 mM). Severity of colitis, inflammatory cytokine and short-chain fatty acid (SCFA) concentration in proximal colon contents, the percentage of IgA-coated bacteria and microbiota composition by 16S ribosomal RNA assessment of stool were measured after 4 weeks of treatment. Sodium butyrate ameliorated histological colitis and decreased levels of tumor necrosis factor (TNF)-α and IL-6 in IL-10^−/− mice compared with those without treatment. At the phylum level, a reduction in Bacteroidetes and an increase in Firmicutes in IL-10^−/− mice treated with sodium butyrate were observed. Additionally, Prevotellaceae species were reduced in IL-10^−/− mice treated with sodium butyrate as compared with those without treatment. The level of biodiversity was slightly increased and the amount of IgA-coated bacteria decreased in IL-10^−/− mice treated with sodium butyrate compared with those without treatment. Our results indicate that sodium butyrate protects against colitis, possibly through modifying the gut microbiota, enriching biodiversity and reducing the amount of colitogenic IgA-coated bacteria in IL-10^−/− mice.

Background: Inflammatory cytokine interleukin‐6 (IL‐6) plays a pivotal role in skeletal muscle degradation after intra‐abdominal sepsis (IAS), with mechanism remained to be elucidated. Indoleamine 2,3‐dioxygenase 1 (IDO‐1), a key enzyme in converting tryptophan into kynurenine, could be activated by IL‐6, and kynurenine has been shown to be involved in muscle degradation. We hypothesized that IL‐6 could promote muscle degradation via tryptophan–IDO‐1–kynurenine pathway in IAS patients.Methods: Serum and rectus abdominis (RA) were obtained from IAS or non‐IAS patients. Mouse model of IAS‐induced muscle wasting was generated by caecal ligation and puncture (CLP) and lipopolysaccharide (LPS) injection. IL‐6 signalling was blocked by anti‐mouse IL‐6 antibody (IL‐6‐AB), and the IDO‐1 pathway was blocked by navoximod. To elucidate the role of kynurenine in muscle mass and physiology, kynurenine was administered to IAS mice treated with IL‐6‐AB.Results: Compared to non‐IAS patients, kynurenine levels in serum (+2.30‐fold vs. non‐IAS, P < 0.001) and RA (+3.11‐fold vs. non‐IAS, P < 0.001) were elevated, whereas tryptophan levels in serum (−53.65% vs. non‐IAS, P < 0.01) and RA (−61.39% vs. non‐IAS, P < 0.01) were decreased. Serum IL‐6 level of the IAS group was significantly higher compared to non‐IAS patients (+5.82‐fold vs. non‐IAS, P = 0.01), and muscle cross‐sectional area (MCSA) was markedly reduced compared to non‐IAS patients (−27.73% vs. non‐IAS, P < 0.01). In animal experiments, IDO‐1 expression was up‐regulated in the small intestine, colon and blood for CLP or LPS‐treated mice, and there was correlation (R² = 0.66, P < 0.01) between serum and muscle kynurenine concentrations. Navoximod significantly mitigated IAS‐induced skeletal muscle loss according to MCSA analysis (+22.94% vs. CLP, P < 0.05; +23.71% vs. LPS, P < 0.01) and increased the phosphorylated AKT (+2.15‐fold vs. CLP, P < 0.01; +3.44‐fold vs. LPS, P < 0.01) and myosin heavy chain (+3.64‐fold vs. CLP, P < 0.01; +2.13‐fold vs. LPS, P < 0.01) protein expression in myocytes. In the presence of anti‐IL‐6 antibody, a significantly decreased IDO‐1 expression was observed in the small intestine, colon and blood in CLP or LPS mice (all P < 0.01), whereas the decrease of MCSA was alleviated (+37.43% vs. CLP + IgG, P < 0.001; +30.72% vs. LPS + IgG, P < 0.001). In contrast, additional supplementation of kynurenine decreased the MCSA in septic mice treated with IL‐6‐AB (both P < 0.01).Conclusions: This study provided novel insights into the tryptophan–IDO‐1–kynurenine‐dependent mechanisms that underlie inflammatory cytokine‐induced skeletal muscle catabolism during intra‐abdominal sepsis.