Gut microbiota-derived metabolite pantetheine modulates host lipid metabolism to protect against obesity

ABSTRACT:

Obesity is intricately linked to the gut microbiota, yet the microbial effectors and molecular mechanisms that mediate this association remain poorly defined. Fecal microbiome analysis revealed a consistent depletion of the commensal bacterium Roseburia inulinivorans in obese individuals, with its relative abundance inversely correlating with adiposity. This inverse correlation was recapitulated in diet-induced obese mice. Supplementation with R. inulinivorans or its encapsulated form in these mice attenuated high-fat diet-induced weight gain and improved metabolic parameters. Subsequent metabolomic profiling of murine samples identified pantetheine as a key metabolite derived from R. inulinivorans. Administration of pantetheine alone was sufficient to recapitulate the anti-obesity effects observed with bacterial supplementation. Mechanistically, pantetheine modulates adrenergic receptor signaling and directly inhibits lipid droplet accumulation in adipocytes. These findings establish a causal gut-adipose axis wherein R. inulinivorans-derived pantetheine regulates host lipid metabolism to protect against obesity, revealing a novel target for microbiome-based metabolic therapeutics.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase

PROVIDER: MTBLS13142 | MetaboLights | 2025-10-15

REPOSITORIES: MetaboLights