Bovine colostrum-derived exosomes alleviate muscle degeneration by modulating gut microbiota and metabolic homeostasis in atrophy models
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Sarcopenia, a condition characterized by chronic systemic inflammation and a significant decline in the quality of life, is primarily associated with aging and degenerative diseases. Several studies have shown that milk exosomes contain a substantial number of miRNAs that are involved in immunity, inflammation, osteoporosis, and gut microbiota regulation. This study aimed to evaluate the potential functional role of bovine colostrum-derived exosomes (BCE) in reducing muscle atrophy. BCE treatment enhanced the viability of C2C12 myotube and stimulated myogenic differentiation, while inhibiting muscle atrophy markers MuRF1 and atrogin-1 that were upregulated by dexamethasone (DEX) exposure. In Caenorhabditis elegans, BCE supplementation significantly prolonged lifespan and upregulated key myogenic structural genes, such as myo-3 and unc-54. BCE also modulated gut microbiome composition by significantly increasing Lachnospiraceae abundance while promoting an increase in Muribaculaceae and a decrease in Bacteroidaceae levels. These microbial changes were associated with a reduction in cholesterol levels in DEX-treated mice. Furthermore, BCE restored metabolic homeostasis by reversing DEX-induced alterations in succinic acid and L-Alanine levels, both of which are critical for muscle metabolism and lipid regulation. Taken together, our findings support the role of BCE in modulating gut microbiota and metabolites, highlighting the therapeutic potential of BCE in counteracting muscle atrophy.
Abstract
Sarcopenia, a condition characterized by chronic systemic inflammation and a significant decline in the quality of life, is primarily associated with aging and degenerative diseases. Several studies have shown that milk exosomes contain a substantial number of miRNAs that are involved in immunity, inflammation, osteoporosis, and gut microbiota regulation. This study aimed to evaluate the potential functional role of bovine colostrum-derived exosomes (BCE) in reducing muscle atrophy. BCE treatment enhanced the viability of C2C12 myotube and stimulated myogenic differentiation, while inhibiting muscle atrophy markers MuRF1 and atrogin-1 that were upregulated by dexamethasone (DEX) exposure. In Caenorhabditis elegans, BCE supplementation significantly prolonged lifespan and upregulated key myogenic structural genes, such as myo-3 and unc-54. BCE also modulated gut microbiome composition by significantly increasing Lachnospiraceae abundance while promoting an increase in Muribaculaceae and a decrease in Bacteroidaceae levels. These microbial changes were associated with a reduction in cholesterol levels in DEX-treated mice. Furthermore, BCE restored metabolic homeostasis by reversing DEX-induced alterations in succinic acid and L-Alanine levels, both of which are critical for muscle metabolism and lipid regulation. Taken together, our findings support the role of BCE in modulating gut microbiota and metabolites, highlighting the therapeutic potential of BCE in counteracting muscle atrophy.