Synbiotic Intervention with Inulin and Lactiplantibacillus plantarum LPm77 Attenuates Type 2 Diabetes via Enhanced TUDCA Metabolism and Gut–Liver Axis Modulation

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by inflammation and immune dysregulation, with the gut–liver axis playing a crucial role in immunometabolic balance. While dietary fibers show therapeutic potential, their mechanisms in T2DM remain unclear. This study investigates the effects of synbiotic intervention combining inulin and Lactiplantibacillus plantarum LPm77 on T2DM, focusing on the gut–liver axis. After 7 weeks of synbiotic treatment, significant improvements in hyperglycemia, insulin resistance, and hepatic steatosis were observed in T2DM mice. Inulin promoted L. plantarum LPm77 colonization, enhancing the gut microbiota balance and restoring the intestinal barrier function. It also regulated bile acid levels in the enterohepatic circulation. The synbiotic promoted tauro-ursodeoxycholic acid (TUDCA) biosynthesis, improving hepatic lipid metabolism and activating TGR5. TGR5 activation suppressed M1 macrophage polarization via the TGR5-TLR4-NF-κB pathway, reducing pro-inflammatory cytokines and increasing IL-10, thus alleviating systemic inflammation. This study highlights a novel therapeutic approach targeting immune-metabolic dysregulation in T2DM.