Li Minghan, Guo Jialin, Meng Jinxin, Wang Xueting, Pan Tianxu, Zhao Dongyu, Li Hongye, Gao Ruyi, Wang Ya, Li Hechun, Li Songyang, Wang Jiagan, Huang Haibin, Wang Nan, Yu Shuyuan, Guan Jiayao, Liu Mingxiao, Wang Chunfeng, Yang Guilian
College of Veterinary Medicine, Jilin Agricultural University, Changchun, Jilin 130118, China.
Jilin Provincial Engineering Research Center of Animal Probiotics, and Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Jilin Agricultural University, Changchun, Jilin 130118, China.
J Agric Food Chem. 2025 Aug 6;73(31):19442-19459. doi: 10.1021/acs.jafc.5c03515. Epub 2025 Jul 25.
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 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 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.
2型糖尿病（T2DM）是一种以炎症和免疫失调为特征的代谢紊乱疾病，其中肠-肝轴在免疫代谢平衡中起关键作用。虽然膳食纤维具有治疗潜力，但其在T2DM中的作用机制尚不清楚。本研究调查了菊粉与LPm77联合合生元干预对T2DM的影响，重点关注肠-肝轴。经过7周的合生元治疗，T2DM小鼠的高血糖、胰岛素抵抗和肝脂肪变性有显著改善。菊粉促进了LPm77的定殖，增强了肠道微生物群平衡并恢复了肠道屏障功能。它还调节了肠肝循环中的胆汁酸水平。合生元促进了牛磺熊去氧胆酸（TUDCA）的生物合成，改善了肝脏脂质代谢并激活了TGR5。TGR5激活通过TGR5-TLR4-NF-κB途径抑制M1巨噬细胞极化，减少促炎细胞因子并增加IL-10，从而减轻全身炎症。本研究突出了一种针对T2DM免疫代谢失调的新型治疗方法。
