Composition of gut microbiota involved in alleviation of dexamethasone-induced muscle atrophy by whey protein

Skeletal muscle atrophy is a condition associated with increased morbidity and mortality. While the concept of the gut-muscle axis has been proposed, the role of gut microbiota in dexamethasone (DEX)-induced skeletal muscle atrophy remains largely unknown, limiting its clinical applications. In this study, we found that administration of DEX caused a shift in the gut microbiota of mice, characterized by an increased ratio of Firmicutes/Bacteroidota and a reduction in alpha diversity. We also identified 480 new operational taxonomic units (OTUs), while 1168 specific OTUs were lost. Our Spearman correlation analysis revealed 28 key taxonomic genera of bacteria that were positively or negatively associated with skeletal muscle strength and weight (r: −0.881 to 0.845, p < 0.05). Moreover, supplementation with whey protein reshaped the gut microbiota structure in DEX-treated mice, making it more similar to that of the control group. Importantly, we further utilized a stepwise regression model to identify two enterotypes capable of predicting skeletal muscle function and weight. Notably, Ileibacterium and Lachnospiraceae_UCG-001 played significant roles in predicting both skeletal muscle function and weight. Our findings suggest that DEX causes shifts in the gut microbiota, which can be reversed by whey protein intervention. The enterotypes identified by our stepwise regression models predict muscle function and weight, underscoring the potential role of gut microbiota in modulating muscle atrophy and emphasizing the therapeutic opportunities of microbiota-altering interventions.