Targeting Catenibacterium mitsuokai with icariin modulates gut microbiota and improves hepatic lipid metabolism in intrauterine growth restriction

ISME J. 2025 Jul 3:wraf141. doi: 10.1093/ismejo/wraf141. Online ahead of print.

Abstract

Male offspring with intrauterine growth restriction exhibit more pronounced hepatic lipid metabolism abnormalities than females, necessitating earlier intervention. Icariin has been shown to effectively modulate hepatic lipid metabolism in male piglets with intrauterine growth restriction. However, the role of gut microbiota in this process remains to be elucidated. This study aimed to explore the influence of gut microbiota on icariin-induced enhancement of hepatic lipid metabolism. By examining changes in microbiota composition and hepatic lipid metabolism following icariin intervention, the study demonstrated an association between microbial alterations and hepatic lipid regulation through fecal microbiota transplantation. The impact of Catenibacterium on gut microbiota structure and hepatic lipid metabolism was assessed in vivo, and the direct effect of icariin on Catenibacterium was explored in vitro. Results revealed that icariin intervention modified fecal, ileal, and colonic microbiota in male piglets with intrauterine growth restriction, enhanced gut morphology and barrier function, and normalized the expression of hepatic peroxisome proliferator-activated receptor (PPAR) signaling pathway-related genes. Fecal microbiota transplantation from piglets with intrauterine growth restriction impaired intestinal barrier function and led to hepatic lipid deposition, whereas transplantation from icariin-treated donors showed no pathological changes, an outcome associated with reduced abundance of Catenibacterium. Mechanistically, icariin inhibits adenosine triphosphate synthesis to suppress Catenibacterium, remodels gut microbiota, reduces lipopolysaccharide production and translocation, and activates the hepatic PPARα/CD36 axis. In conclusion, icariin intervention alleviates hepatic lipid metabolic disorders in male offspring with intrauterine growth restriction by suppressing Catenibacterium, restoring gut microbial balance, and enhancing intestinal barrier integrity to limit lipopolysaccharide translocation.

Keywords: Catenibacterium; IUGR; Piglet; cariin; icrobiota; ipid metabolism.