PP205 - CURCUMIN IMPROVED SEPSIS-RELATED MUSCLE INJURY VIA "INTESTINE-BILE ACID-FXR" AXIS

PP205

CURCUMIN IMPROVED SEPSIS-RELATED MUSCLE INJURY VIA "INTESTINE-BILE ACID-FXR" AXIS

N. Lin^1,*, J. LIU¹

¹Clinical Nutrition, The General Hospital Of Western Theater Command, Chengdu, China

Rationale: This study aims to investigate the effects of curcumin on sepsis-related skeletal muscle injury and elucidate its potential mechanism of action on skeletal muscle via the "gut-bile acid-FXR" axis.

Methods: C57BL/6J mice were intraperitoneally injected with LPS to establish a sepsis-related muscle injury mouse model.  Curcumin was administered orally at a dose of 150 mg/kg for 14 days, while the model group received an equivalent volume of physiological saline. Fecal samples were subjected to metagenomic analysis. Non-targeted metabolomics and bile acid-targeted metabolomic analysis were conducted. Furthermore, a pseudo-germ-free mouse model was created to verify of role gut microbiota played. The protein expression of FXR and FGF15/19 in the ileum and ERK1/2 and p90RSK in the skeletal muscle were detected.

Results: Curcumin intervention could improve the forelimb grip strength and decrease the expression of muscle atrophy markers Murf1 and Fbx32, with an increase of the amount of muscle fibers and alteration of the composition ratio of type I and type II fibers. Curcumin increased the abundance of beneficial bacteria. Tests in pseudo-germ-free mouse model showed that the protective effect of curcumin relied on gut microbiota. Non-targeted metabolomics indicated that metabolites were enriched in bile acid metabolism pathways and bile acid-targeted metabolomic results revealed that curcumin could also alter the composition of bile acids in mice, especially those act as endogenous antagonists of FXR. Curcumin could upregulate the expression of FXR in the ileum, activated the production of FGF15/19 in the ileal epithelium. The ERK1/2 signaling pathway was enhanced and its downstream factor p90RSK was also activated. 

Conclusion: Our research results indicate that curcumin has the effect of improving sepsis-related muscle injury, which is dependent on gut microbiota via bile acid metabolism.

Disclosure of Interest: None declared