Bone loss with aging is independent of gut microbiome in mice  

作　　者：Xiaomeng You Jing Yan Jeremy Herzog Sabah Nobakhti Ross Campbell Allison Hoke Rasha Hammamieh R.Balfour Sartor Sandra Shefelbine Melissa A.Kacena Nabarun Chakraborty Julia F.Charles 

机构地区：[1]Department of Orthopaedic Surgery,Brigham and Women’s Hospital,Harvard Medical School,Boston,MA 02115,USA [2]National Gnotobiotic Rodent Resource Center,Center for Gastrointestinal Biology and Disease,University of North Carolina at Chapel Hill,Chapel Hill,NC 27599,USA [3]Department of Mechanical and Industrial Engineering,Northeastern University,Boston,MA 02115,USA [4]The Geneva Foundation,Walter Reed Army Institute of Research,Silver Spring,MD 20910,USA [5]Medical Readiness Systems Biology,Walter Reed Army Institute of Research,Silver Spring,MD 20910,USA [6]ORISE,Walter Reed Army Institute of Research,Silver Spring,MD 20910,USA [7]Department of Orthopaedic Surgery,Indiana University School of Medicine,Indianapolis,IN 46202,USA [8]Richard L.Roudebush VA Medical Center,Indianapolis,IN 46202,USA [9]Division of Rheumatology,Brigham and Women’s Hospital,Harvard Medical School,Boston,MA 02115,USA

出　　处：《Bone Research》2024年第4期980-993,共14页骨研究(英文版)

基　　金：supported by NIH grants R01 AG046257 (JFC);the Orthopaedic Scholar Fund;the Department of Orthopaedic Surgery,Brigham and Women’s Hospital,P30 AR075042;the Joint Biology Consortium funded by P30-AR070253;performed at National Gnotobiotic Rodent Resource Center at University of North Carolina at Chapel Hill,funded by P40-OD010995,P30-DK034987;Crohn’s and Colitis Foundation;supported with resources and the use of facilities at the Richard L.Roudebush VA Medical Center,Indianapolis,IN:VA Merit#BX003751。

摘　　要：Emerging evidence suggests a significant role of gut microbiome in bone health.Aging is well recognized as a crucial factor influencing the gut microbiome.In this study,we investigated whether age-dependent microbial change contributes to age-related bone loss in CB6F1 mice.The bone phenotype of 24-month-old germ-free(GF)mice was indistinguishable compared to their littermates colonized by fecal transplant at 1-month-old.Moreover,bone loss from 3 to 24-month-old was comparable between GF and specific pathogen-free(SPF)mice.Thus,GF mice were not protected from age-related bone loss.16S rRNA gene sequencing of fecal samples from 3-month and 24-month-old SPF males indicated an age-dependent microbial shift with an alteration in energy and nutrient metabolism potential.An integrative analysis of 16S predicted metagenome function and LC-MS fecal metabolome revealed an enrichment of protein and amino acid biosynthesis pathways in aged mice.Microbial S-adenosyl methionine metabolism was increased in the aged mice,which has previously been associated with the host aging process.Collectively,aging caused microbial taxonomic and functional alteration in mice.To demonstrate the functional importance of young and old microbiome to bone,we colonized GF mice with fecal microbiome from 3-month or 24-month-old SPF donor mice for 1 and 8 months.The effect of microbial colonization on bone phenotypes was independent of the microbiome donors’age.In conclusion,our study indicates age-related bone loss occurs independent of gut microbiome.

关 键 词：METABOLISM AGING ALTERATION 

分 类 号：R580[医药卫生—内分泌]