Limosilactobacillus reuteri ATG-F4 Ameliorates Dexamethasone-Induced Muscle Atrophy through Modulation of Gut Microbiota

TL;DR

A gut bacterium called Limosilactobacillus reuteri ATG-F4 helps prevent muscle atrophy in mice by improving gut health and muscle metabolism.

Contribution

This study identifies a novel probiotic strain that mitigates muscle atrophy through gut microbiota modulation and metabolic pathways.

Findings

ATG-F4 preserved muscle mass and strength in mice treated with dexamethasone.

The probiotic suppressed muscle atrophy-related genes and activated mitochondrial biogenesis.

ATG-F4 improved gut barrier integrity and increased branched-chain amino acids in muscles.

Abstract

Sarcopenia is a progressive age-related degenerative disorder characterized by the loss of muscle mass, strength, and functional capacity. Although several probiotics have been reported to attenuate muscle atrophy, the underlying mechanisms remain unclear. This study investigated the anti-atrophic potential of Limosilactobacillus reuteri ATG-F4, a human gut-derived bacterium, in a mouse model of dexamethasone (DEX)–induced muscle atrophy. Oral administration of ATG-F4 significantly preserved skeletal muscle mass, improved grip strength, and prevented a decrease in muscle fiber size in DEX-treated mice. Mechanistically, ATG-F4 administration was associated with the downregulation of the expression of Atrogin-1, a major muscle atrophy-related factor, consistent with the suppression of FOXO signaling in the quadriceps femoris (QF). Concurrently, ATG-F4 treatment was associated with the activation of AMPK signaling and increased mitochondrial biogenesis markers (PGC1-α, mtTFA). In addition, ATG-F4 administration prevented DEX-induced disruption of ileal barrier integrity and was associated with changes in the composition of the gut microbiota, with concomitant increases in the levels of branched-chain amino acids (BCAAs) in the cecum and muscle. These results suggest that ATG-F4 may enhance systemic BCAA availability and is associated with the activation of BCAA-mediated energy metabolism and mitochondrial function in skeletal muscles. Overall, these findings highlight the potential of ATG-F4 as a prophylactic or therapeutic agent to prevent or mitigate muscle atrophy.

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