The present study aimed to determine if metformin exerts anti-inflammatory and mucus-protective effects via the gut microbiota. Metformin has extensive benefits including anti-inflammatory effects. Previous studies showed that metformin changed the gut microbiota composition and increases the number of goblet cells. Intestinal dysbiosis and goblet cell depletion are important features of ulcerative colitis (UC). The underlying mechanism and whether metformin can improve the mucus barrier in UC remain unclear. Metformin (400 mg/kg/day) was administered to mice with dextran sulfate sodium (DSS)-induced UC for 2 wk to investigate the effects of metformin on the intestinal mucus barrier. The gut microbiota was depleted, using antibiotics, to explore its role in the mucus-protecting effects of metformin. Akkermansia muciniphila (A. muciniphila), which was enriched in metformin-treated mice, was administered to mice to investigate the effects of the bacteria on UC and the mucus barrier. Metformin attenuated DSS-induced UC in mice, as evidenced by the alleviation of diarrhea, hematochezia, and the decrease in body weight. The expression of mucin2, a prominent mucus barrier protein, was increased in the metformin-treated group compared to the DSS-treated group. Furthermore, fecal 16S rRNA analysis showed that metformin treatment changed the gut microbiota composition by increasing the relative abundance of Lactobacillus and Akkermansia species while decreasing Erysipelatoclostridium at the genus level. Antibiotic treatment partly abolished the anti-inflammatory and mucus-protecting effects of metformin. Administration of A. muciniphila alleviated the colonic inflammation and mucus barrier disruption. Metformin alleviated DSS-induced UC in mice and protected against cell damage via affecting the gut microbiota, thereby providing a new mechanism for the therapeutic effect of metformin in patients with UC. This study also provides evidence that A. muciniphila as a probiotic has potential benefits for UC.
Background: Viable probiotics have shown effects on the eradication of Helicobacter pylori, but the role of non-viable probiotics in H. pylori eradication is unclear. This study aimed to evaluate the effects of non-viable Lactobacillus reuteri DSM17648 combining with 14-day standard triple therapy on H. pylori eradication.
Materials and Methods:Two hundred treatment-naive H. pylori-positive adult patients were randomized equally to receive non-viable L. reuteri DSM17648 (LR group) or placebo for 4 weeks, with the latter 2 weeks treated together with triple therapy.The Gastrointestinal Symptom Rating Scale (GSRS) was completed before and after treatment. Stool samples were collected for 16S rRNA gene sequencing at week0, week2, and week8.
Results:Eradication rates in the LR group and the placebo group were 81.8% and 83.7% in ITT analysis (p = 0.730), 86.2% and 87.2% in PP analysis (p = 0.830), respectively. After treatment, the mean GSRS score decreased significantly in the LR group as compared with the placebo group (1.9 ± 0.2 vs. 2.7 ± 0.3; p = 0.030). Significantly less patients in the LR group as compared with the placebo group reported abdominal distention (5.1% vs. 16.3%; p = 0.010) and diarrhea (11.1% vs. 23.5%; p = 0.022).The relative abundance of Proteobacteria phylum and Escherichia-Shigella genus in the placebo group was about 4.0-fold and 8.1-fold of that in the LR group at wk2, respectively. Significant changes of diversity and enhancements of Fusicatenibacter, Subdoligranulum, and Faecalibacterium were observed in the LR group compared with the placebo group.Conclusions: Supplementation of non-viable L. reuteri DSM17648 with triple therapy did not improve the eradication rate of H. pylori, but it helped to build up a beneficial microbial profile and reduced the frequencies of abdominal distention, diarrhea, and the GSRS score.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.