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

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