문서현 (서울대학교)

문서현 (서울대학교)

Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with gut microbiota dysbiosis, and modulation of the gut-liver axis has emerged as a promising therapeutic approach. In this context, live biotherapeutic products (LBPs) are being investigated as adjuncts to glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy. However, the metabolic responses to this combination is still remain as blackbox. To address this, we performed untargeted LC-MS/MS metabolomics to characterize tissue-specific metabolic alterations following co-administration of semaglutide and two LBP candidates (BZ5 and BZ10131) in a high-fat, high-fructose diet-induced MASLD mouse model.

Metabolomic analysis of liver, brown adipose tissue (BAT), and white adipose tissue (WAT) were analyzed using PCA, PLS-DA, univariate analysis, and multiple linear regression. In the liver, co-treatment with semaglutide and BZ10131 was associated with distinct interaction-related metabolomic changes. In BAT, BZ5 and BZ10131 induced strain-specific metabolic alterations, whereas WAT exhibited metabolic changes associated with both LBP treatment and co-treatment with semaglutide.

Overall, these findings suggest that LBP-GLP-1 combination therapy may induce tissue-specific metabolic responses beyond those observed with individual treatments. The metabolomic signatures identified across liver, BAT, and WAT provide a basis for future phenotypic and multi-omics investigations.