Transplantation of gut microbiota from old mice into young healthy mice reduces lean mass but not bone mass

References

• Janssen I, Shepard DS, Katzmarzyk PT, Roubenoff R. The healthcare costs of sarcopenia in the United States. J Am Geriatr Soc. 2004;52(1):80–15. doi:10.1111/j.1532-5415.2004.52014.x.
   PubMed Web of Science ®Google Scholar
• Hernlund E, Svedbom A, Ivergard M, Compston J, Cooper C, Stenmark J, McCloskey EV, Jönsson B, Kanis JA. Osteoporosis in the European Union: medical management, epidemiology and economic burden. A report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Arch Osteoporos. 2013;8(1–2):136. doi:10.1007/s11657-013-0136-1.
   PubMed Web of Science ®Google Scholar
• Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyere O, Cederholm T, Cooper C, Landi F, Rolland Y, Sayer AA, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019;48(1):16–31. doi:10.1093/ageing/afy169.
   PubMed Web of Science ®Google Scholar
• Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464(7285):59–65. doi:10.1038/nature08821.
   PubMed Web of Science ®Google Scholar
• Antonopoulos DA, Huse SM, Morrison HG, Schmidt TM, Sogin ML, Young VB. Reproducible community dynamics of the gastrointestinal microbiota following antibiotic perturbation. Infect Immun. 2009;77(6):2367–2375. doi:10.1128/IAI.01520-08.
   PubMed Web of Science ®Google Scholar
• Dethlefsen L, Relman DA. Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proc Natl Acad Sci USA. 2011;108(Suppl 1):4554–4561. doi:10.1073/pnas.1000087107.
   PubMed Web of Science ®Google Scholar
• Kau AL, Ahern PP, Griffin NW, Goodman AL, Gordon JI. Human nutrition, the gut microbiome and the immune system. Nature. 2011;474(7351):327–336. doi:10.1038/nature10213.
   PubMed Web of Science ®Google Scholar
• Conlon MA, Bird AR. The impact of diet and lifestyle on gut microbiota and human health. Nutrients. 2014;7(1):17–44. doi:10.3390/nu7010017.
   PubMed Web of Science ®Google Scholar
• Claesson MJ, Jeffery IB, Conde S, Power SE, O’Connor EM, Cusack S, Harris HMB, Coakley M, Lakshminarayanan B, O’Sullivan O, et al. Gut microbiota composition correlates with diet and health in the elderly. Nature. 2012;488(7410):178–184. doi:10.1038/nature11319.
   PubMed Web of Science ®Google Scholar
• Jackson MA, Jeffery IB, Beaumont M, Bell JT, Clark AG, Ley RE, O’Toole PW, Spector TD, Steves CJ. Signatures of early frailty in the gut microbiota. Genome Med. 2016;8(1):8. doi:10.1186/s13073-016-0262-7.
   PubMed Web of Science ®Google Scholar
• Glatt V, Canalis E, Stadmeyer L, Bouxsein ML. Age-related changes in trabecular architecture differ in female and male C57BL/6J mice. J Bone Miner Res. 2007;22(8):1197–1207. doi:10.1359/jbmr.070507.
   PubMed Web of Science ®Google Scholar
• Tavoian D, Lozier NR, de Lacalle S, Anderson RM. Age of peak performance differs by functional task in mice tracked over 2 years. J Gerontol A Biol Sci Med Sci. 2021;76(7):1179–1183. doi:10.1093/gerona/glab048.
   PubMed Web of Science ®Google Scholar
• Sjogren K, Engdahl C, Henning P, Lerner UH, Tremaroli V, Lagerquist MK, Bäckhed F, Ohlsson C. The gut microbiota regulates bone mass in mice. J Bone Miner Res. 2012;27(6):1357–1367. doi:10.1002/jbmr.1588.
   PubMed Web of Science ®Google Scholar
• Yu M, D’Amelio P, Tyagi AM, Vaccaro C, Li JY, Hsu E, Buondonno I, Sassi F, Adams J, Weitzmann MN, et al. Regulatory T cells are expanded by Teriparatide treatment in humans and mediate intermittent PTH-induced bone anabolism in mice. EMBO Rep. 2018;19(1):156–171. doi:10.15252/embr.201744421.
   PubMed Web of Science ®Google Scholar
• Tyagi AM, Yu M, Darby TM, Vaccaro C, Li JY, Owens JA, Hsu E, Adams J, Weitzmann MN, Jones RM, et al. The microbial metabolite butyrate stimulates bone formation via T regulatory cell-mediated regulation of WNT10B Expression. Immunity. 2018;49(6):1116–1131.e7. doi:10.1016/j.immuni.2018.10.013.
   PubMed Web of Science ®Google Scholar
• Gregg R, Smith CM, Clark FJ, Dunnion D, Khan N, Chakraverty R, Nayak L, Moss PA. The number of human peripheral blood CD4+ CD25high regulatory T cells increases with age. Clin Exp Immunol. 2005;140(3):540–546. doi:10.1111/j.1365-2249.2005.02798.x.
   PubMed Web of Science ®Google Scholar
• Garg SK, Delaney C, Toubai T, Ghosh A, Reddy P, Banerjee R, Yung R. Aging is associated with increased regulatory T-cell function. Aging Cell. 2014;13(3):441–448. doi:10.1111/acel.12191.
   PubMed Web of Science ®Google Scholar
• Ohlsson C, Sjogren K. Effects of the gut microbiota on bone mass. Trends Endocrinol Metab. 2015;26(2):69–74. doi:10.1016/j.tem.2014.11.004.
   PubMed Web of Science ®Google Scholar
• Zaiss MM, Jones RM, Schett G, Pacifici R. The gut-bone axis: how bacterial metabolites bridge the distance. J Clin Invest. 2019;129(8):3018–3028. doi:10.1172/JCI128521.
   PubMed Web of Science ®Google Scholar
• McNabney SM, Henagan TM. Short chain fatty acids in the colon and peripheral tissues: A focus on butyrate, colon cancer, obesity and insulin resistance. Nutrients. 2017;9(12):1348. doi:10.3390/nu9121348.
   PubMed Web of Science ®Google Scholar
• Lucas S, Omata Y, Hofmann J, Bottcher M, Iljazovic A, Sarter K, Albrecht O, Schulz O, Krishnacoumar B, Krönke G, et al. Short-chain fatty acids regulate systemic bone mass and protect from pathological bone loss. Nat Commun. 2018;9(1):55. doi:10.1038/s41467-017-02490-4.
   PubMedGoogle Scholar
• Ohlsson C, Engdahl C, Fak F, Andersson A, Windahl SH, Farman HH, Movérare-Skrtic S, Islander U, Sjögren K. Probiotics protect mice from ovariectomy-induced cortical bone loss. PLoS One. 2014;9(3):e92368. doi:10.1371/journal.pone.0092368.
   PubMed Web of Science ®Google Scholar
• Britton RA, Irwin R, Quach D, Schaefer L, Zhang J, Lee T, Parameswaran N, McCabe LR. Probiotic L. reuteri treatment prevents bone loss in a menopausal ovariectomized mouse model. J Cell Physiol. 2014;229(11):1822–1830. doi:10.1002/jcp.24636.
   PubMed Web of Science ®Google Scholar
• Li JY, Chassaing B, Tyagi AM, Vaccaro C, Luo T, Adams J, Darby TM, Weitzmann MN, Mulle JG, Gewirtz AT, et al. Sex steroid deficiency–associated bone loss is microbiota dependent and prevented by probiotics. J Clin Invest. 2016;126(6):2049–2063. doi:10.1172/JCI86062.
   PubMed Web of Science ®Google Scholar
• Dar HY, Shukla P, Mishra PK, Anupam R, Mondal RK, Tomar GB, Sharma V, Srivastava RK. Lactobacillus acidophilus inhibits bone loss and increases bone heterogeneity in osteoporotic mice via modulating Treg-Th17 cell balance. Bone Rep. 2018;8:46–56. doi:10.1016/j.bonr.2018.02.001.
   PubMedGoogle Scholar
• Dar HY, Pal S, Shukla P, Mishra PK, Tomar GB, Chattopadhyay N, Srivastava RK. Bacillus clausii inhibits bone loss by skewing Treg-Th17 cell equilibrium in postmenopausal osteoporotic mice model. Nutrition. 2018;54:118–128. doi:10.1016/j.nut.2018.02.013.
   PubMed Web of Science ®Google Scholar
• Montazeri-Najafabady N, Ghasemi Y, Dabbaghmanesh MH, Talezadeh P, Koohpeyma F, Gholami A. Supportive role of probiotic strains in protecting rats from ovariectomy-induced cortical bone loss. Probiotics Antimicrob Proteins. 2019;11(4):1145–1154. doi:10.1007/s12602-018-9443-6.
   PubMed Web of Science ®Google Scholar
• Nilsson AG, Sundh D, Backhed F, Lorentzon M. Lactobacillus reuteri reduces bone loss in older women with low bone mineral density: a randomized, placebo-controlled, double-blind, clinical trial. J Intern Med. 2018;284(3):307–317. doi:10.1111/joim.12805.
   PubMed Web of Science ®Google Scholar
• Jansson PA, Curiac D, Ahrén IL, Hansson F, Niskanen TM, Sjögren K, Ohlsson C. Probiotic treatment using a mix of three Lactobacillus strains for lumbar spine bone loss in postmenopausal women: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet Rheumatol. 2019;1(3):e154–62. doi:10.1016/S2665-9913(19)30068-2.
   PubMedGoogle Scholar
• Lahiri S, Kim H, Garcia-Perez I, Reza MM, Martin KA, Kundu P, Cox LM, Selkrig J, Posma JM, Zhang H, et al. The gut microbiota influences skeletal muscle mass and function in mice. Sci Transl Med. 2019;11(502):11. doi:10.1126/scitranslmed.aan5662.
   Web of Science ®Google Scholar
• Hsu YJ, Chiu CC, Li YP, Huang WC, Huang YT, Huang CC, Chuang HL. Effect of intestinal microbiota on exercise performance in mice. J Strength Cond Res. 2015;29(2):552–558. doi:10.1519/JSC.0000000000000644.
   PubMed Web of Science ®Google Scholar
• Manickam R, Oh HYP, Tan CK, Paramalingam E, Wahli W. Metronidazole causes skeletal muscle atrophy and modulates muscle chronometabolism. Int J Mol Sci. 2018;19(8):2418. doi:10.3390/ijms19082418.
   PubMed Web of Science ®Google Scholar
• Okamoto T, Morino K, Ugi S, Nakagawa F, Lemecha M, Ida S, Ohashi N, Sato D, Fujita Y, Maegawa H, et al. Microbiome potentiates endurance exercise through intestinal acetate production. Am J Physiol Endocrinol Metab. 2019;316(5):E956–E966. doi:10.1152/ajpendo.00510.2018.
   PubMed Web of Science ®Google Scholar
• Nay K, Jollet M, Goustard B, Baati N, Vernus B, Pontones M, Lefeuvre-Orfila L, Bendavid C, Rué O, Mariadassou M, et al. Gut bacteria are critical for optimal muscle function: a potential link with glucose homeostasis. Am J Physiol Endocrinol Metab. 2019;317(1):E158–E171. doi:10.1152/ajpendo.00521.2018.
   PubMed Web of Science ®Google Scholar
• Walsh ME, Bhattacharya A, Sataranatarajan K, Qaisar R, Sloane L, Rahman MM, Kinter M, Van Remmen H. The histone deacetylase inhibitor butyrate improves metabolism and reduces muscle atrophy during aging. Aging Cell. 2015;14(6):957–970. doi:10.1111/acel.12387.
   PubMed Web of Science ®Google Scholar
• Ni Y, Yang X, Zheng L, Wang Z, Wu L, Jiang J, Yang T, Ma L, Fu Z. Lactobacillus and bifidobacterium improves physiological function and cognitive ability in aged mice by the regulation of gut microbiota. Mol Nutr Food Res. 2019;63(22):e1900603. doi:10.1002/mnfr.201900603.
   PubMed Web of Science ®Google Scholar
• Chen LH, Huang SY, Huang KC, Hsu CC, Yang KC, Li LA, Chan C-H, Huang H-Y. Lactobacillus paracasei PS23 decelerated age-related muscle loss by ensuring mitochondrial function in SAMP8 mice. Aging (Albany NY). 2019;11(2):756–770. doi:10.18632/aging.101782.
   PubMedGoogle Scholar
• Chen YM, Wei L, Chiu YS, Hsu YJ, Tsai TY, Wang MF, Huang C-C. Lactobacillus plantarum TWK10 supplementation improves exercise performance and increases muscle mass in mice. Nutrients. 2016;8(4):205. doi:10.3390/nu8040205.
   PubMed Web of Science ®Google Scholar
• Huang WC, Lee MC, Lee CC, Ng KS, Hsu YJ, Tsai TY, Young S-L, Lin J-S, Huang C-C. Effect of lactobacillus plantarum TWK10 on exercise physiological adaptation, performance, and body composition in healthy humans. Nutrients. 2019;11(11):11. doi:10.3390/nu11112836.
   Web of Science ®Google Scholar
• Faith JJ, Ahern PP, Ridaura VK, Cheng J, Gordon JI. Identifying gut microbe–host phenotype relationships using combinatorial communities in gnotobiotic mice. Sci Transl Med. 2014;6(220):220ra11. doi:10.1126/scitranslmed.3008051.
   PubMed Web of Science ®Google Scholar
• Halloran BP, Ferguson VL, Simske SJ, Burghardt A, Venton LL, Majumdar S. Changes in bone structure and mass with advancing age in the male C57BL/6J mouse. J Bone Miner Res. 2002;17(6):1044–1050. doi:10.1359/jbmr.2002.17.6.1044.
   PubMed Web of Science ®Google Scholar
• Langille MG, Meehan CJ, Koenig JE, Dhanani AS, Rose RA, Howlett SE, Beiko RG. Microbial shifts in the aging mouse gut. Microbiome. 2014;2(1):50. doi:10.1186/s40168-014-0050-9.
   PubMed Web of Science ®Google Scholar
• Binyamin D, Werbner N, Nuriel-Ohayon M, Uzan A, Mor H, Abbas A, Ziv O, Teperino R, Gutman R, Koren O, et al. The aging mouse microbiome has obesogenic characteristics. Genome Med. 2020;12(1):87. doi:10.1186/s13073-020-00784-9.
   PubMed Web of Science ®Google Scholar
• You X, Dadwal UC, Lenburg ME, Kacena MA, Charles JF, Rawls JF. Murine gut microbiome meta-analysis reveals alterations in carbohydrate metabolism in response to aging. mSystems. 2022;7(2):e0124821. doi:10.1128/msystems.01248-21.
   PubMed Web of Science ®Google Scholar
• Low A, Soh M, Miyake S, Seedorf H, Xu ZZ. Host age prediction from fecal microbiota composition in male C57BL/6J mice. Microbiol Spectr. 2022;10(3):e0073522. doi:10.1128/spectrum.00735-22.
   PubMed Web of Science ®Google Scholar
• Wang N, Ma S, Fu L. Gut microbiota dysbiosis as one cause of osteoporosis by impairing intestinal barrier function. Calcif Tissue Int. 2022;110(2):225–235. doi:10.1007/s00223-021-00911-7.
   PubMed Web of Science ®Google Scholar
• Tan H, Zhao J, Zhang H, Zhai Q, Chen W. Novel strains of Bacteroides fragilis and Bacteroides ovatus alleviate the LPS-induced inflammation in mice. Appl Microbiol Biotechnol. 2019;103(5):2353–2365. doi:10.1007/s00253-019-09617-1.
   PubMed Web of Science ®Google Scholar
• Hamady ZZ, Scott N, Farrar MD, Lodge JP, Holland KT, Whitehead T, Carding SR. Xylan-regulated delivery of human keratinocyte growth factor-2 to the inflamed colon by the human anaerobic commensal bacterium Bacteroides ovatus. Gut. 2010;59(4):461–469. doi:10.1136/gut.2008.176131.
   PubMed Web of Science ®Google Scholar
• Hamady ZZ, Scott N, Farrar MD, Wadhwa M, Dilger P, Whitehead TR, Thorpe R, Holland KT, Lodge PJA, Carding SR, et al. Treatment of colitis with a commensal gut bacterium engineered to secrete human TGF-β1 under the control of dietary xylan. Inflamm Bowel Dis. 2011;17(9):1925–1935. doi:10.1002/ibd.21565.
   PubMed Web of Science ®Google Scholar
• Ihekweazu FD, Fofanova TY, Queliza K, Nagy-Szakal D, Stewart CJ, Engevik MA, Hulten KG, Tatevian N, Graham DY, Versalovic J, et al. Bacteroides ovatus ATCC 8483 monotherapy is superior to traditional fecal transplant and multi-strain bacteriotherapy in a murine colitis model. Gut Microbes. 2019;10(4):504–520. doi:10.1080/19490976.2018.1560753.
   PubMed Web of Science ®Google Scholar
• Han ND, Cheng J, Delannoy-Bruno O, Webber D, Terrapon N, Henrissat B, Rodionov DA, Arzamasov AA, Osterman AL, Hayashi DK, et al. Microbial liberation of N-methylserotonin from orange fiber in gnotobiotic mice and humans. Cell. 2022;185(16):3056–3057. doi:10.1016/j.cell.2022.07.007.
   PubMed Web of Science ®Google Scholar
• Horvath TD, Ihekweazu FD, Haidacher SJ, Ruan W, Engevik KA, Fultz R, Hoch KM, Luna RA, Oezguen N, Spinler JK, et al. Bacteroides ovatus colonization influences the abundance of intestinal short chain fatty acids and neurotransmitters. iScience. 2022;25(5):104158. doi:10.1016/j.isci.2022.104158.
   PubMed Web of Science ®Google Scholar
• Koh A, De Vadder F, Kovatcheva-Datchary P, Backhed F. From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites. Cell. 2016;165(6):1332–1345. doi:10.1016/j.cell.2016.05.041.
   PubMed Web of Science ®Google Scholar
• Al-Khaldi SF, Martin SA, Prakash L. Fermentation of fenugreek fiber, psyllium husk, and wheat bran by Bacteroides ovatus V975. Curr Microbiol. 1999;39(4):231–232. doi:10.1007/s002849900450.
   PubMed Web of Science ®Google Scholar
• Lawenius L, Collden H, Gustafsson KL, Wu J, Grahnemo L, Vandenput L, Ohlsson C, Sjögren K. A probiotic mix partially protects against castration-induced bone loss in male mice. J Endocrinol. 2022;254(2):91–101. doi:10.1530/JOE-21-0408.
   PubMed Web of Science ®Google Scholar
• Asvold BO, Langhammer A, Rehn TA, Kjelvik G, Grontvedt TV, Sorgjerd EP, Fenstad JS, Heggland J, Holmen O, Stuifbergen MC, et al. Cohort profile update: The HUNT study, Norway. Int J Epidemiol. 2023;52(1):e80–e91. doi:10.1093/ije/dyac095.
   PubMed Web of Science ®Google Scholar
• Krokstad S, Langhammer A, Hveem K, Holmen TL, Midthjell K, Stene TR, Bratberg G, Heggland J, Holmen J. Cohort profile: the HUNT Study, Norway. Int J Epidemiol. 2013;42(4):968–977. doi:10.1093/ije/dys095.
   PubMed Web of Science ®Google Scholar
• De Caceres M, Legendre P. Associations between species and groups of sites: indices and statistical inference. Ecology. 2009;90(12):3566–3574. doi:10.1890/08-1823.1.
   PubMed Web of Science ®Google Scholar
• Edgar RC. MUSCLE: a multiple sequence alignment method with reduced time and space complexity. BMC Bioinform. 2004;5(1):113. doi:10.1186/1471-2105-5-113.
   PubMed Web of Science ®Google Scholar
• Price MN, Dehal PS, Arkin AP, Poon AFY. FastTree 2–approximately maximum-likelihood trees for large alignments. PLoS One. 2010;5(3):e9490. doi:10.1371/journal.pone.0009490.
   PubMed Web of Science ®Google Scholar
• Team RDC. The R project for statistical computing. Vienna, Austria: The R Foundation for Statistical Computing; 2022.
   Google Scholar
• McMurdie PJ, Holmes S, Watson M. Phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data. PLoS One. 2013;8(4):e61217. doi:10.1371/journal.pone.0061217.
   PubMed Web of Science ®Google Scholar
• Lozupone C, Knight R. UniFrac: a new phylogenetic method for comparing microbial communities. Appl Environ Microbiol. 2005;71(12):8228–8235. doi:10.1128/AEM.71.12.8228-8235.2005.
   PubMed Web of Science ®Google Scholar
• Oksanen J, Blanchet FG, Friendly M, Kindt R, Legendre P, McGlin D, Minchin P.R, O’hara R.B, Simpson G.L, Solymos P, et al. Vegan: Community ecology package. R Package Version 2 4-3. 2017. https://cran.r-project.org/web/packages/vegan/index.html.
   Google Scholar
• Chao A. Nonparametric estimation of the number of classes in a population. Scand J Stat. 1984;11:265–270.
   Web of Science ®Google Scholar
• Simpson EH. Measurement of Diversity. Nature. 1949;163(4148):688–688. doi:10.1038/163688a0.
   Web of Science ®Google Scholar
• Shannon CE. A mathematical theory of communication. Bell Syst Tech J. 1948;27(3):379–423. doi:10.1002/j.1538-7305.1948.tb01338.x.
   Google Scholar
• Segata N, Izard J, Waldron L, Gevers D, Miropolsky L, Garrett WS, Huttenhower C. Metagenomic biomarker discovery and explanation. Genome Biol. 2011;12(6):R60. doi:10.1186/gb-2011-12-6-r60.
   PubMed Web of Science ®Google Scholar
• Moverare-Skrtic S, Henning P, Liu X, Nagano K, Saito H, Borjesson AE, Sjögren K, Windahl SH, Farman H, Kindlund B, et al. Osteoblast-derived WNT16 represses osteoclastogenesis and prevents cortical bone fragility fractures. Nat Med. 2014;20(11):1279–1288. doi:10.1038/nm.3654.
   PubMed Web of Science ®Google Scholar
• Grahnemo L, Nethander M, Coward E, Gabrielsen ME, Sree S, Billod JM, Engstrand L, Abrahamsson S, Langhammer A, Hveem K, et al. Cross-sectional associations between the gut microbe Ruminococcus gnavus and features of the metabolic syndrome. Lancet Diabetes Endocrinol. 2022;10:481–483. doi:10.1016/S2213-8587(22)00113-9.
   PubMed Web of Science ®Google Scholar