UNLABELLED: Type 2 diabetes mellitus (T2DM) mainly induced by high-fat diets (HFD) is becoming a prevalent and serious metabolic disease worldwide. Although probiotics are considered a treatment for T2DM, the underlying mechanisms and therapeutic effects of the specific strain remain unclear. Thus, elucidating the strain-dependent mechanisms and identifying effective probiotic strains for T2DM management are critically needed. In this study,was administered to HFD-induced T2DM mice to evaluate its effects on fasting blood glucose (FBG), body weight (BW), gut microbiota (GM) composition, gut metabolites, and liver gene expression. We found thatsupplementation significantly reduced FBG, insulin levels, and BW, while ameliorating liver and pancreatic damage in T2DM mice. Furthermore, shifts in gut microbial composition were observed followingintervention, characterized by the suppression of,,sp., and bacterium D1676, along with enrichment of beneficial strains, such as,sp. P55, and. Besides,administration significantly increased the concentrations of glycocholic acid, arachidonic acid, L-tryptophan, and palmitic acid while decreasing chenodeoxycholic acid concentration. This modulation is accompanied by the upregulation ofandmRNA expression, leading to increased levels of(G protein-coupled bile receptor) and(Glucagon-like peptide-1 receptor). Transcriptomic and metabolomic analyses confirmed thatalleviates T2DM caused by HFD through upregulating the bile acid secretion pathway. The results demonstrate thatameliorates symptoms in T2DM mice through the gut-liver axis. Lactobacillus plantarum L. plantarum L. plantarum Lactobacillus johnsonii Bacteroides acidifaciens Alistipes L. acidophilus Enterorhabdus Bacteroides caecimuris L. plantarum Hmgcr Ugt1a5TGR5GLP1R L. plantarum L. plantarum
IMPORTANCE: T2DM is becoming a global health problem linked to poor diet and metabolic disorders. The probioticoffers a promising natural approach by targeting two key factors: gut bacteria balance and bile acid function. In HFD-fed mice, this treatment helps restore healthy gut microbes and improves bile acid signaling, which together lower blood glucose, reduce inflammation, and protect against liver damage. Unlike many diabetes medications,works with the body's natural systems, potentially providing a safer, long-term solution. This research highlights how probiotics could complement existing therapies, offering novel therapeutic strategies for diabetes treatment through the gut-liver axis. L. plantarum L. plantarum
