LPS-related muscle loss is associated with the alteration of Bacteroidetes abundance,systemic inflammation,and mitochondrial morphology in a weaned piglet model  

作　　者：Jiayi Yu Changbing Zheng Qiuping Guo Yulong Yin Yehui Duan Fengna Li 

机构地区：[1]CAS Key Laboratory of Agro-ecological Processes in Subtropical Region,Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process,National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production,Institute of Subtropical Agriculture,Chinese Academy of Sciences,Changsha 410125,China [2]University of Chinese Academy of Sciences,Beijing 100049,China [3]College of Animal Science and Technology,Hunan Agricultural University,Changsha 410128,China

出　　处：《Science China(Life Sciences)》2024年第9期1970-1988,共19页中国科学（生命科学英文版）

基　　金：supported by the National Natural Science Foundation of China(32372925);the Science and Technology Innovation Program of Hunan Province(2022RC1159);the Changsha Natural Science Funds for Distinguished Young Scholar(kq2009020);the National Key Research and Development Programs of China(2022YFD1300503);the China Agriculture Research System of MOF and MARA(CARS35)。

摘　　要：We previously demonstrated that lipopolysaccharide(LPS)injection-induced immune stress could impair muscle growth in weaned piglets,but the precise mechanisms behind this remain elusive.Here,we found that chronic immune stress induced by LPS resulted in a significant reduction of 36.86%in the total muscle mass of piglets at 5 d post-treatment compared with the control group.At 1 d,prior to muscle mass loss,multiple alterations were noted in response to LPS treatment.These included a reduction in the abundance of Bacteroidetes,an increase in serum concentrations of pro-inflammatory cytokines,compromised mitochondrial morphology,and an upregulation in the expression of dynamin-related protein 1(Drp1),a critical protein involved in mitochondrial fission.We highlight a strong negative correlation between Bacteroidetes abundance and the levels of serum pro-inflammatory cytokines,corroborated by in vivo intervention strategies in the musculature of both pig and mouse models.Mechanistically,the effects of Bacteroidetes on inflammation and muscle mass loss may involve the signaling pathway of the tauro-β-muricholic acid-fibroblast growth factor 15.Furthermore,the induction of overexpression of inflammatory cytokines,achieved without LPS treatment through oral administration of recombinant human IL-6(rh IL-6),led to increased levels of circulating cytokines,subsequently causing a decrease in muscle mass.Notably,pre-treatment with Mdivi-1,an inhibitor of Drp-1,markedly attenuated the LPS-induced elevation in reactive oxygen species levels and rescued the associated decline in muscle mass.Collectively,these data indicate that LPS-induced muscle mass loss was linked to the reduction of Bacteroidetes abundance,increased inflammation,and the disruption of mitochondrial morphology.These insights offer promising avenues for the identification of potential therapeutic targets aimed at mitigating muscle mass loss.

关 键 词：BACTEROIDETES inflammation mitochondrial morphology muscle mass loss PIGLETS 

分 类 号：S852[农业科学—基础兽医学]