Meng Yan, Dandan Pan, Libang Chen, Jiale Pang, Yuting Shao, Qian Cheng, Ying Liu, Zeyuan Yin, Zhenzhou Jiang, Pian Sha, Yuqian Huang, Yilin Fan, Sitong Qian, Tao Wang, Qian Lü, Tingting Yang
Probiotic supplementation was a novel therapeutic approach for treating metabolic related diseases via "gut-liver" axis. However, the effect of Clostridium butyricum (CB) supplementation on type 2 diabetes mellitus (T2DM)-associated steatohepatitis was unknown. This study revealed that CB alleviated liver damage and hepatitis in 18 weeks-old db/db mice. Targeted metabolomics analysis showed that the dysregulated short chain fatty acids (SCFAs) metabolism homeostasis was regained by CB in the colon content of db/db mice, especially butyric acid. Treatment with sodium butyrate (NaB) significantly attenuated steatosis, inflammation, and fibrosis of db/db mice, and high glucose (HG) and free fatty acid (FFA) co-treated HepG2 cells. In-depth mechanism research suggested that the hepatoprotective effects of CB on T2DM was associated with the suppression of IκB-α/β-arrestin2/NF-κB signaling pathway via intestinal butyrate-medicated hepatic Takeda G-protein-coupled receptor 5 (TGR5). Overall, our results demonstrated a potential novel mechanism for CB as effective nutritional intervention for T2DM-related steatohepatitis via "gut-liver" axis.