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Abstract Maintaining the mucus layer is crucial for the innate immune system. Urolithin A (Uro A) is a gut microbiota-derived metabolite; however, its effect on mucin production as a physical barrier remains unclear. This study aimed to elucidate the protective effects of Uro A on mucin production in the colon. In vivo experiments employing wild-type mice, NF-E2-related factor 2 (Nrf2)-deficient mice, and wild-type mice treated with an aryl hydrocarbon receptor (AhR) antagonist were conducted to investigate the physiological role of Uro A. Additionally, in vitro assays using mucin-producing cells (LS174T) were conducted to assess mucus production following Uro A treatment. We found that Uro A thickened murine colonic mucus via enhanced mucin 2 expression facilitated by Nrf2 and AhR signaling without altering tight junctions. Uro A reduced mucosal permeability in fluorescein isothiocyanate-dextran experiments and alleviated dextran sulfate sodium-induced colitis. Uro A treatment increased short-chain fatty acid-producing bacteria and propionic acid concentration. LS174T cell studies confirmed that Uro A promotes mucus production through the AhR and Nrf2 pathways. In conclusion, the enhanced intestinal mucus secretion induced by Uro A is mediated through the actions of Nrf-2 and AhR, which help maintain intestinal barrier function.

Abstract Colonic mucus layers protect intestinal tissues against intestinal bacteria. We investigated the effects of dietary fiber and its metabolites on mucus production in the colonic mucosa. Mice were fed a partially hydrolyzed guar gum (PHGG)-containing diet and a fiber-free diet (FFD). The colon mucus layer, fecal short-chain fatty acid (SCFA) levels, and gut microbiota were evaluated. Mucin 2 (MUC2) expression was assessed in SCFA-treated LS174T cells. The role of AKT in MUC2 production was investigated. The mucus layer in the colonic epithelium was significantly increased in the PHGG group compared with that in the FFD group. In the PHGG group, an increase in Bacteroidetes in the stool was observed, and fecal acetate, butyrate, propionate, and succinate levels were significantly increased. However, MUC2 production was significantly increased only in succinate-stimulated LS174T cells. The succinate-induced MUC2 production was associated with AKT phosphorylation. Succinate mediated the PHGG-induced increase in the colon mucus layer.

Introduction: Although the efficacy of 5-aminosalicylic acid (ASA) suppositories for ulcerative colitis (UC) has been reported in many studies, many studies have also described poor adherence to 5-ASA suppository regimens. We aimed to identify the clinical background factors that influence adherence to 5-ASA suppositories to improve adherence and efficacy of the treatment. Methods: We conducted a retrospective cohort study of 61 patients with active UC who were using 5-ASA suppositories. All patients underwent endoscopy and rectal biopsy for histological diagnosis prior to 5-ASA suppository treatment. The efficacy of 5-ASA suppository treatment was compared in relation to clinical background factors (sex, age, disease duration, disease type, clinical activity, Ulcerative Colitis Endoscopic Index of Severity, histological activity, serum C-reactive protein level, concomitant use of immunomodulators, history of steroid use, and dose of oral 5-ASA). Results: The efficacy of 5-ASA suppositories was significantly related to low Lichtiger Colitis Activity Index (LCAI) scores and proctitis type prior to its use. In terms of sex, females tended to show higher efficacy. Multivariate logistic regression analysis using these three factors showed high predictive value for the efficacy of 5-ASA suppositories (AUC, 0.788; sensitivity, 87.2%; and specificity, 63.7%). Conclusion: This study is the first to extract clinical background factors for predicting the efficacy of 5-ASA suppositories. The use of 5-ASA suppositories in patients who are expected to show efficacy will be effective in improving patient co-operation.

Abstract Background Nonalcoholic fatty liver disease is characterized by excessive hepatic fat accumulation. Some individuals frequently present elevated gamma-glutamyl transferase (GGT) levels without fatty liver ultrasound images and other abnormal liver enzymes levels. However, whether these individuals are at an elevated risk for developing fatty liver is unclear. We compared fatty liver change rates and risk factors between individuals with frequently elevated GGT levels and those with normal levels. Methods We designed a retrospective cohort study on the basis of complete medical checkup records. One group of individuals had presented normal serum GGT levels during the observation period (Normal-GGT group, n = 2713). Another group had had abnormal elevated serum GGT levels frequently (Abnormal-GGT group, n = 264). We determined the fatty liver change incident rates before and after propensity score matching. We explored confounding factors affecting fatty changes in each group using univariate and multivariate Cox models. Results The change incidence rates were 5.80/1000 and 10.02/1000 person-years in the Normal-GGT and Abnormal-GGT groups, respectively. After propensity score matching, the incidence rates were 3.08/1000 and 10.18/1000 person-years in the Normal-GGT and Abnormal-GGT groups, respectively (p = 0.026). The factors associated with fatty liver changes in the Normal-GGT group included body mass index (BMI), hemoglobin, alanine aminotransferase (ALT), albumin, triglyceride (TG), fasting blood sugar, and high-density lipoprotein levels. Those in the Abnormal-GGT group were platelet counts and TG. In our multivariable analysis, BMI, ALT, albumin, and TG levels were independent predictors of fatty changes in the Normal-GGT group, and high TG level was the only independent predictor in the Abnormal-GGT group. Conclusions The incidence rate of fatty liver change in the Abnormal-GGT group was higher than that in the Normal-GGT group. Consecutive elevated GGT levels increase the risk for fatty liver, and high TG levels in those individuals further independently increase the risk.