Sodium Butyrate Limits Skeletal Muscle Stem Cells Activation Induced By Gut Microbiota Disturbance

Although antibiotics are widely used to treat many life-threatening infections and study of symbiotic microbiota,our understanding of their effects on hosts is still very limited,especially on muscles.Skeletal muscle,as a metabolic,thermogenic and endocrine organ,plays an important role in maintaining the energy balance and metabolism of the body.Myofibers are the functional contractile units of skeletal muscle.Skeletal muscle stem cells located between the muscle cell membrane and the muscle fiber basement membrane and have the potential of self-renewal and regeneration function.Skeletal muscle stem cells are the basis of muscle injury and repair.However,the relationship between the status of skeletal muscle stem cells and intestinal microorganisms and their metabolites is still unknown.In order to explore the relationship between the state of skeletal muscle stem cells and gut microbiota disturbance with Antibiotics of mice and better understand the interaction between microbiota,antibiotics and hosts,we added penicillin,kanamycin,neomycin,penicillin,vancomycin,Gentamicin(0.3mg/ml)to mice.The effect of antibiotics and microbial metabolism on the activation of skeletal muscle stem cells was discussed by changing the important metabolite of microflora,sodium butyrate.The body weight of mice was measured continuously and fecal samples were collected.DNA was extracted from fecal samples and the V3-4 region of 16s rDNA gene was sequenced.The sequences of quality filtering are processed by QIIME and analyzed in R statistical environment.Myofibers of extensor digitorum longus were isolated and skeletal muscle stem cells and their activation were analyzed by immunofluorescence staining.Total RNA,was extracted to analyze the transcription level of differentiation marker MyoD(Myogenic Differentiation)and MyoG(Myogenin)in different type of skeletal muscle.We have shown that antibiotics treatment activates some quiescent skeletal muscle stem cells.After the application of antibiotics,the gut microbiota of mice was disordered,the diversity of gut microbiota was significantly decreased,and the distribution of community was significantly changed.Random forest algorithm predicted that Bacteroides acidifaciens may be the key gut microbiota after antibiotic treatment.It was shown that the administration of Bacteroides acidifaciens can lead to the reduction of butyrate in feces.Our targeted metabolomics data confirmed the change of butyrate.We found that the addition of sodium butyrate inhibited the differentiation of skeletal muscle stem cells,but had no significant effect on the proliferation of skeletal muscle stem cells,resulting in an increase in the number of skeletal muscle stem cells.The addition of sodium butyrate can partially reverse the activation state of mouse skeletal muscle stem cells induced by antibiotics,suggesting that the activation of skeletal muscle stem cells induced by antibiotics may be related to the metabolism of sodium butyrate.