Lactobacillus gasseri CBT LGA2 alleviates muscle protein degradation and inflammation in immobilization-induced mouse.

2026-01-07
Frontiers in microbiology 16

PubMed: 41574345
DOI: 10.3389/fmicb.2025.1728172

Study Design

Population: C2C12 myotubes and RAW264.7 macrophages; hindlimb immobilization mouse model
Methods: Five probiotic strains were screened in C2C12 myotubes and RAW264.7 macrophages to assess anti-proteolytic and anti-inflammatory activities; whole-genome sequencing was conducted; in vivo efficacy was evaluated using a hindlimb immobilization mouse model administered with Lactobacillus gasseri CBT LGA2 (1 × 10^8 CFU/kg/day, 3 weeks), followed by assessments of muscle mass, grip strength, fiber morphology, and molecular markers

Introduction

Hindlimb immobilization rapidly induces skeletal muscle atrophy by reducing mechanical loading and accelerating proteolytic activity. This atrophy is further exacerbated by inflammatory signaling, which amplifies FOXO3a-driven expression of Atrogin-1 and MuRF1 and suppresses myogenic capacity. Emerging evidence suggests that specific probiotic strains may counteract these catabolic and inflammatory responses, prompting the evaluation of Lactobacillus gasseri CBT LGA2 (LGA2) in this study.

Methods

In the present study, five probiotic strains were screened in C2C12 myotubes and RAW264.7 macrophages to assess anti-proteolytic and anti-inflammatory activities. Whole-genome sequencing was conducted to determine genetic safety and functional gene profiles. In vivo efficacy was evaluated using a hindlimb immobilization mouse model administered with LGA2 (1 × 10^⁸ CFU/kg/day, 3 weeks), followed by assessments of muscle mass, grip strength, fiber morphology, and molecular markers.

Results

LGA2 showed the strongest suppression of dexamethasone-induced muscle protein degradation and lipopolysaccharides-induced inflammatory responses among the screened strains. Genomic analysis identified genes related to antioxidant defense, immune modulation, and muscle protection. In immobilized mice, LGA2 significantly improved grip strength, preserved muscle mass, and restored muscle fiber cross-sectional area. Mechanistically, LGA2 maintained FOXO3a phosphorylation, reduced Atrogin-1 and MuRF1 expression, and recovered myogenin and MyHC isoforms (IIa, IIx, IIb). Additionally, LGA2 lowered TNF-α, IL-6, iNOS, and COX-2 levels while restoring IL-10 in muscle and serum.

Discussion

These findings demonstrate that LGA2 mitigates disuse-induced muscle atrophy through coordinated anti-inflammatory, anti-proteolytic, and pro-myogenic mechanisms. Its genomic safety and multifunctional efficacy support LGA2 as a promising probiotic intervention for muscle health.

Research Insights

Supplement	Dose	Health Outcome	Effect Type	Effect Size	Source
Lactobacillus gasseri	—	Reduced Inflammation	Beneficial	Moderate	View source Additionally, LGA2 lowered TNF-α, IL-6, iNOS, and COX-2 levels while restoring IL-10 in muscle and serum.