Limosilactobacillus fermentum ANC4 (KCTC 15072BP) Mitigates Dexamethasone-Induced Muscle Atrophy and Improves Overall Skeletal Muscle Function.

Glucocorticoid-induced muscle atrophy involves accelerated protein breakdown and impaired regeneration. We evaluated the protective effects of heat-killed and live Limosilactobacillus fermentum ANC4 against dexamethasone (Dex)-induced muscle wasting in C57BL/6 mice. Oral administration of L. fermentum ANC4 significantly improved grip strength and treadmill endurance while specifically preserving the mass of the gastrocnemius (GCM), a fast-twitch-dominant muscle. Mechanistically, L. fermentum ANC4 downregulated the glucocorticoid receptor (GR) and E3 ubiquitin ligases, including muscle RING-finger protein-1 (MuRF-1) and Atrogin-1, thereby mitigating catabolic signaling. Simultaneously, it up-regulated myogenic regenerative markers, including myogenic differentiation 1 (MyoD), myogenin, and myosin heavy chain (MyHC). Histological analysis confirmed that muscle fiber size restored and reduced fibrosis. Notably, the heat-killed form effectively increased MyHC, while the live form strongly suppressed Atrogin-1. These findings suggest that L. fermentum ANC4 prevents muscle atrophy by balancing catabolic signaling and myogenic repair, highlighting its potential as a probiotic or postbiotic therapy for preserving muscle mass and function.