Lactobacillus plantarum alleviates the symptoms of type 2 diabetes mellitus mice induced by high-fat diet through modulating the gut microbiota and bile acids secretion

Type 2 diabetes mellitus (T2DM) caused by high-fat diets (HFD) is a globally prevalent and severe metabolic disorder. Although probiotic intervention has been proposed as a therapeutic strategy for T2DM, the mechanisms underlying the strain specific therapeutic effects remain unclear. Thus, elucidating the strain dependent mechanisms and identifying effective probiotic strains for T2DM management are critically needed. In this study, Lactobacillus plantarum was administered to HFD-induced T2DM mice to evaluate its effects on fasting blood glucose (FBG), body weight (BW), gut microbiota composition, gut metabolites, and liver gene expression. We found that L. plantarum supplementation significantly reduced FBG, insulin levels, and BW, while ameliorating liver and pancreatic damage in T2DM mice. Furthermore, L. plantarum altered gut microbiota composition by suppressing detrimental bacteria such as Lactobacillus johnsonii, Bacteroides acidifaciens, Alistipes sp, and bacterium D1676, while enriching beneficial strains including Lactobacillus acidophilus, Enterorhabdus sp P55, and Bacteroides caecimuris. Besides, the administration of L. plantarum significantly increased the concentrations of glycocholic acid, arachidonic acid, L-tryptophan, and palmitic acid, while concurrently reducing chenodeoxycholic acid level. This modulation is accompanied by the upregulation of Hmgcr and Ugt1a5 mRNA expression, it led to increase in G protein-coupled bile receptor (TGR5) and Glucagon-like peptide-1 receptor (GLP1R) gene level. Transcriptomic and metabolomic analyses confirmed that L. plantarum alleviates T2DM caused by HFD-induced by upregulating the bile acid secretion pathway. These findings suggest that L. plantarum holds promise in ameliorating T2DM and may serve as a potential probiotics supplement for patients with T2DM.