Myostatin gene deletion alters gut microbiota stimulating fast-twitch glycolytic muscle growth

Abstract

The host genome may influence the composition of the intestinal microbiota, and intestinal microbiota performs an important role in muscle growth and development. Here, we showed that Myostatin (MSTN), a key factor for muscle growth, deletion alters muscularis, plica, and intestinal barrier in pigs. Mice transplanted with MSTN−/− pig intestinal flora showed increase in the cross-sectional area of myofibers and fast-twitch glycolytic muscle mass. The microbes responsible for the production of short chain fatty acids (SCFAs) were enriched in both MSTN−/− pigs and recipient mice, and SCFAs levels were elevated in the colon contents. We demonstrated that valeric acid can stimulate type IIb myofiber growth by activation of the Akt/mTOR pathway via GPR43 and improve muscle atrophy induced by dexamethasone. This is the first study to identify the MSTN gene-gut microbiota-SCFA axis and its regulatory role in fast-twitch glycolytic muscle growth.

Revitalizing the Gut Microbiome in Chronic Kidney Disease: A Comprehensive Exploration of the Therapeutic Potential of Physical Activity

“…As MSTN inhibits the formation of skeletal muscles, large increases in muscle mass and strength have been seen in animals lacking MSTN [ 139 ]. MSTN is mostly expressed in skeletal muscles [ 139 ], although it is also present in smooth muscles, such as the gut, where it is involved in a number of metabolic activities [ 140 ]. Pei et al showed that the gut microbiota composition in MSTN mutant pigs is altered [ 141 ].…”

“…Pei et al showed that the gut microbiota composition in MSTN mutant pigs is altered [ 141 ]. Similarly, Luo et al discovered that deletion of the MSTN gene modifies the gut microbiome, promoting the formation of fast-twitch glycolytic muscle in mice [ 140 ]. Interestingly, resistance training for a minimum of five weeks was found to be beneficial in lowering myostatin levels in healthy people [ 142 ].…”

“…CKD is associated with increased expression of myostatin [ 139 ]. This is significant because lower myostatin levels have a beneficial effect on the gut microbiota [ 140 , 141 ]. Therefore, it can be stated that an increase in this myokine negatively influences the gut microbiome.…”

When Less Is More: Targeting the Myostatin Gene in Livestock for Augmenting Meat Production

“…One of these MSTN -edited models, its progeny, or its crosses were further investigated . These include investigations on fiber-type distribution and expression of myosin heavy chain isoforms; shift from slow- to fast-twitch muscle fibers in skeletal muscle; internal organ size; semen quality and fertilization ability; reproductive trait characterization in MSTN -edited crosses; collagen-related pathological features (umbilical hernia and tippy toe standing); regulation of body fat deposition; fibrinogen levels and fibrin clot structure; esophageal striated muscle development and regulation of muscle fiber types; extraocular muscles; cardiac extracellular matrix; growth of smooth muscle in uterine horns of MSTN mutant gilts; smooth muscle content in corpus cavernosum of MSTN mutant boars; erythrocyte osmotic fragility, hematological parameters, and fatty acid composition of serum and erythrocyte membranes; miR-455-3p regulation of myoblast differentiation; composition and alteration of gut microbiota; analysis of meat and fatty acids characteristics; and development of a restriction enzyme-mediated PCR-RFLP assay for genotyping MSTN mutant pigs …”