Clostridium sporogenes and its tryptophan metabolite indole -3- propionic acid repair antibiotic-induced muscle atrophy in mice.

Antibiotic-induced dysbiosis of the gut microbiota disrupts essential nutrient metabolism and bioactive compound production, contributing to systemic health deterioration including skeletal muscle atrophy. This study assessed the reparative effects of Clostridium sporogenes (CS) and its metabolite indole-3-propionic acid (IPA) on antibiotic-induced muscle atrophy in mice. A 14-day antibiotic treatment resulted in approximately a 90% reduction of gut microbiota in the mice, leading to an 11.92% decrease in grip strength and muscle atrophy characterized by a 31.22% reduction in myofiber diameter. After an 18-day intervention, both CS and IPA treatments effectively reversed these impairments, achieving over 60% grip strength recovery, near-normal muscle mass weight, and morphology. Notably, CS demonstrated superior myofiber recovery, with a diameter recovery rate of 31.74%, approximately double that of IPA-treated mice. Mechanistically, both CS and IPA enriched short-chain fatty acid (SCFA)-producing gut microbes such as Lachnospiraceae and Lactobacillaceae, positively reconstructing the microbiota and improving metabolic profiles. Specifically, the treatments restored IPA homeostasis, activated amino acid metabolic pathways including tryptophan and glutamate, and reduced toxic metabolites like chlorobenzene. Additionally, the expression of myogenic factors (Myf5, Pax3, Pax7) and atrophy-related genes (Atrogin-1, MuRF-1) returned to baseline levels in treated mice. These findings highlight the therapeutic potential of CS and IPA as nutritional interventions to mitigate antibiotic-associated muscle loss through microbial restoration, modulation of key metabolic pathways, and preservation of protein homeostasis.