机构:[1]Sichuan Univ, West China Hosp, Natl Clin Res Ctr Geriatr, Chengdu, Peoples R China四川大学华西医院[2]Sichuan Univ, West China Hosp, Dept Geriatr, Chengdu, Peoples R China四川大学华西医院[3]Sichuan Univ, West China Hosp, West China Biomed Big Data Ctr, West China Sch Med, Chengdu, Peoples R China四川大学华西医院[4]Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands[5]Chengdu Univ Tradit Chinese Med, Dept Basic Med, Chengdu, Peoples R China[6]Southwest Med Univ, Affiliated Tradit Chinese Med Hosp, Luzhou, Sichuan, Peoples R China[7]Sichuan Univ, West China Hosp, Canc Ctr, Collaborat Innovat Ctr Biotherapy, Chengdu, Peoples R China四川大学华西医院[8]Univ Elect Sci & Technol, Sichuan Canc Hosp & Inst, Sichuan Canc Ctr, Dept Med oncol,Med Sch, Chengdu, Peoples R China四川省肿瘤医院[9]Sichuan Univ, Medx Ctr Informat, Chengdu, Peoples R China[10]Sichuan Univ, Coll Life Sci, Chengdu, Peoples R China[11]Univ Groningen, Univ Med Ctr Groningen, Dept Pediat, Groningen, Netherlands[12]Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Chengdu, Peoples R China四川大学华西医院
BackgroundThe gut microbiome and fecal metabolites have been found to influence sarcopenia, but whether there are potential bacteria that can alleviate sarcopenia has been under-investigated, and the molecular mechanism remains unclear. MethodsTo investigate the relationships between the gut microbiome, fecal metabolites and sarcopenia, subjects were selected from observational multi-ethnic study conducted in Western China. Sarcopenia was diagnosed according to the criteria of the Asian Working Group for Sarcopenia 2014. The gut microbiome was profiled by shotgun metagenomic sequencing. Untargeted metabolomic analysis was performed to analyse the differences in fecal metabolites. We investigated bacterium with the greatest relative abundance difference between healthy individuals and sarcopenia patients, and the differences in metabolites associated with the bacteria, to verify its effects on muscle mass and function in a mouse model. ResultsThe study included 283 participants (68.90% females, mean age: 66.66 years old) with and without sarcopenia (141 and 142 participants, respectively) and from the Han (98 participants), Zang (88 participants) and Qiang (97 participants) ethnic groups. This showed an overall reduction (15.03% vs. 20.77%, P = 0.01) of Prevotella copri between the sarcopenia and non-sarcopenia subjects across the three ethnic groups. Functional characterization of the differential bacteria showed enrichment (odds ratio = 15.97, P = 0.0068) in branched chain amino acid (BCAA) metabolism in non-sarcopenia group. A total of 13 BCAA and their derivatives have relatively low levels in sarcopenia. In the in vivo experiment, we found that the blood BCAA level was higher in the mice gavaged with live P. copri (LPC) (P < 0.001). The LPC mice had significantly longer wire and grid hanging time (P < 0.02), longer time on rotor (P = 0.0001) and larger grip strength (P < 0.0001), indicating better muscle function. The weight of gastrocnemius mass and rectus femoris mass (P < 0.05) was higher in LPC mice. The micro-computed tomography showed a larger leg area (P = 0.0031), and a small animal analyser showed a higher lean mass ratio in LPC mice (P = 0.0157), indicating higher muscle mass. ConclusionsThe results indicated that there were lower levels of both P. copri and BCAA in sarcopenia individuals. In vivo experiments, gavage with LPC could attenuate muscle mass and function decline, indicating alleviating sarcopenia. This suggested that P. copri may play a therapeutic potential role in the management of sarcopenia.
基金:
National Natural Science
Foundation of China (No. 82101653 and No. 32100927),
Project of the Sichuan Province Science and Technology (No.
2021YFS0158), National Clinical Research Center for Geriatric,
West China Hospital, Sichuan University (Z2018B09), West
China Hospital Postdoctoral Fund (2020HXBH011), 1.3.5 Project for Disciplines of Excellence,West China Hospital, Sichuan
University, Project of Max Cynader Academy of Brain Workstation,WCHSCU (HXYS19005), Chengdu Science and Technology
Bureau Major Science and Technology Application Demonstration Project (2019YF0900083SN), China Scholarship Council (CSC 202108510037), Dutch Heart Foundation IN-CONTROL
(CVON2018-27), the ERC Consolidator Grant (grant agreement
No. 101001678), NWO-VICI Grant (VI.C.202.022), and The
Netherlands Organ-on-Chip Initiative, an NWO Gravitation
Project (024.003.001).
语种:
外文
被引次数:
WOS:
PubmedID:
中科院(CAS)分区:
出版当年[2023]版:
大类|1 区医学
小类|1 区老年医学1 区医学:内科
最新[2023]版:
大类|1 区医学
小类|1 区老年医学1 区医学:内科
JCR分区:
出版当年[2023]版:
Q1GERIATRICS & GERONTOLOGYQ1MEDICINE, GENERAL & INTERNAL
最新[2023]版:
Q1GERIATRICS & GERONTOLOGYQ1MEDICINE, GENERAL & INTERNAL
第一作者机构:[1]Sichuan Univ, West China Hosp, Natl Clin Res Ctr Geriatr, Chengdu, Peoples R China[2]Sichuan Univ, West China Hosp, Dept Geriatr, Chengdu, Peoples R China
共同第一作者:
通讯作者:
通讯机构:[1]Sichuan Univ, West China Hosp, Natl Clin Res Ctr Geriatr, Chengdu, Peoples R China[2]Sichuan Univ, West China Hosp, Dept Geriatr, Chengdu, Peoples R China[3]Sichuan Univ, West China Hosp, West China Biomed Big Data Ctr, West China Sch Med, Chengdu, Peoples R China[9]Sichuan Univ, Medx Ctr Informat, Chengdu, Peoples R China[*1]National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 37, Guo Xue Xiang Renmin Nan Lu Chengdu 610041, Sichuan, China[*2]West China Biomedical Big Data Center, West China Hospital/West China School of Medicine, Sichuan University, Chengdu 610041, China.
推荐引用方式(GB/T 7714):
Liu Xiaolei,Wu Jiqiu,Tang Jingyi,et al.Prevotella copri alleviates sarcopenia via attenuating muscle mass loss and function decline[J].JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE.2023,doi:10.1002/jcsm.13313.
APA:
Liu, Xiaolei,Wu, Jiqiu,Tang, Jingyi,Xu, Zhigang,Zhou, Bailing...&Dong, Birong.(2023).Prevotella copri alleviates sarcopenia via attenuating muscle mass loss and function decline.JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE,,
MLA:
Liu, Xiaolei,et al."Prevotella copri alleviates sarcopenia via attenuating muscle mass loss and function decline".JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE .(2023)