Protective Effects of Microbiome-Derived Inosine on Lipopolysaccharide-Induced Acute Liver Damage and Inflammation in Mice via Mediating the TLR4/NF-κB Pathway

This research assessed the anti-inflammatory and hepatoprotective properties of inosine and the associated mechanism. Inosine pretreatment significantly reduced the secretion of several inflammatory factors and serum alanine transaminase (ALT) and aspartate amino transferase (AST) levels in a dose-dependent manner compared with the lipopolysaccharide (LPS) group. In LPS-treated mice, inosine pretreatment significantly reduced the ALT and malondialdehyde (MDA) concentration and significantly elevated the antioxidant enzyme activity. Furthermore, inosine pretreatment significantly altered the relative abundance of the genera, Bifidobacterium, Lachnospiraceae UCG-006, and Muribaculum. Correlation analysis showed that Bifidobacterium and Lachnospiraceae UCG-006 were positively related to the cecal short-chain fatty acids but negatively related to the serum IL-6 and hepatic AST and ALT levels. Notably, inosine pretreatment significantly modulated the hepatic TLR4, MYD88, NF-kappa B, iNOS, COX2, AMPK, Nfr2, and I kappa B-alpha expression. These results suggested that inosine pretreatment alters the intestinal microbiota structure and improves LPS-induced acute liver damage and inflammation through modulating the TLR4/NF-kappa B signaling pathway.

Automated summary

The research assessed the protective effects of inosine on liver injury and inflammation by modulating the intestinal microbiota structure and TLR4/NF-kappa B signaling pathway in LPS-treated mice. Inosine pretreatment significantly reduced inflammatory factors secretion, ALT and AST levels, and improved antioxidant enzyme activity and relative abundance of certain genera. The results suggest that inosine pretreatment has the potential for preventing LPS-induced acute liver damage through its regulatory effects on both intestinal microbiota and hepatic signaling pathways.