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Lactobacillus reuteri ATG-F4-Mediated Amelioration of Muscle Atrophy: Role of Gut Microbiota Composition and Short-Chain Fatty Acids

Daeyoung Lee*, Young-Sil Lee, Gun-Seok Park, Juyi Park, Seung-Hyun Ko, You-Kyung Lee, Do Yeun Jeong, Yong Hyun Lee, Jihee Kang

Probiotics offer a promising avenue for combating muscle atrophy, a debilitating condition associated with disuse, aging and disease. This study investigated the anti-atrophic potential of Lactobacillus reuteri ATG-F4, a human gutderived bacterium, in a staple-induced immobilization mouse model. ATG-F4 administration significantly preserved muscle mass and improved grip strength and endurance, compared to disused controls. Mechanistically, ATG-F4 activated mammalian Target of Rapamycin (mTOR) signalling, promoting protein synthesis, while downregulating MuRF1, a key atrophy factor. Furthermore, ATG-F4 treatment demonstrably altered the gut microbiota composition, favoring the Muribaculaceae family and decreasing Lachnospiraceae and Lactobacillaceae. This regulation suggests that it may increase serum levels of the Short-Chain Fatty Acids (SCFAs) butyrate and acetate. These SCFAs are known to possess anti-inflammatory and muscle-beneficial properties. Therefore, this study suggests a novel mechanism for ATG-F4's anti-atrophic muscle: Enhancing muscle protein synthesis, suppressing protein degradation and modulating the gut microbiota-SCFA axis. These findings highlight the potential of ATG-F4 as a promising prophylactic or therapeutic agent for combating muscle atrophy.