{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:23:51Z","timestamp":1791923031420,"version":"4.3.4"},"reference-count":44,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2016YFC1201805"],"award-info":[{"award-number":["2016YFC1201805"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2017YFC1001100"],"award-info":[{"award-number":["2017YFC1001100"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81770878"],"award-info":[{"award-number":["81770878"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010256","name":"Guangzhou Municipal Science and Technology Project","doi-asserted-by":"publisher","award":["201604020007"],"award-info":[{"award-number":["201604020007"]}],"id":[{"id":"10.13039\/501100010256","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U54MD007595"],"award-info":[{"award-number":["U54MD007595"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG061917"],"award-info":[{"award-number":["R01AG061917"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01MH104680"],"award-info":[{"award-number":["R01MH104680"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P20GM109036"],"award-info":[{"award-number":["P20GM109036"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AR069055"],"award-info":[{"award-number":["R01AR069055"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U19AG05537301"],"award-info":[{"award-number":["U19AG05537301"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2021,12]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Increasing evidence suggests that human gut microbiome plays an important role in variation of skeletal muscle mass (SMM). However, specific causal mechanistic relationship of human gut microbiome with SMM remains largely unresolved. Understanding the causal mechanistic relationship may provide a basis for novel interventions for loss of SMM. This study investigated whether human gut microbiome has a causal effect on SMM among Chinese community\u2010dwelling healthy menopausal women.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Estimated SMM was derived from whole\u2010body dual\u2010energy X\u2010ray absorptiometry. We performed integrated analyses on whole\u2010genome sequencing, shotgun metagenomic sequencing, and serum short\u2010chain fatty acids (SCFAs), as well as available host SMM measurements among community\u2010dwelling healthy menopausal women (\n N<\/jats:italic>\n \u00a0=\u00a0482). We combined the results with summary statistics from genome\u2010wide association analyses for human gut microbiome (\n N<\/jats:italic>\n \u00a0=\u00a0952) and SMM traits (\n N<\/jats:italic>\n \u00a0=\u00a028\u00a0330). As a prerequisite for causality, we used a computational protocol that was proposed to measure correlations among gut metagenome, metabolome, and the host trait to investigate the relationship between human gut microbiome and SMM. Causal inference methods were applied to assess the potential causal effects of gut microbial features on SMM, through one\u2010sample and two\u2010sample Mendelian randomization (MR) analyses, respectively.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In metagenomic association analyses, the increased capacity for gut microbial synthesis of the SCFA butyrate was significantly associated with serum butyrate levels [Spearman correlation coefficient (SCC)\u00a0=\u00a00.13,\n P<\/jats:italic>\n \u00a0=\u00a00.02] and skeletal muscle index (SCC\u00a0=\u00a00.084,\n P<\/jats:italic>\n \u00a0=\u00a00.002). Of interest was the finding that two main butyrate\u2010producing bacterial species were both positively associated with the increased capacity for gut microbial synthesis of butyrate [\n \n Faecalibacterium prausnitzii<\/jats:italic>\n <\/jats:styled-content>\n (SCC\u00a0=\u00a00.25,\n P<\/jats:italic>\n \u00a0=\u00a06.6\u00a0\u00d7\u00a010\n \u22127<\/jats:sup>\n ) and\n \n Butyricimonas virosa<\/jats:italic>\n <\/jats:styled-content>\n (SCC\u00a0=\u00a00.15,\n P<\/jats:italic>\n \u00a0=\u00a00.001)] and for skeletal muscle index [\n \n F.\u00a0prausnitzii<\/jats:italic>\n <\/jats:styled-content>\n (SCC\u00a0=\u00a00.16,\n P<\/jats:italic>\n \u00a0=\u00a06.2\u00a0\u00d7\u00a010\n \u22124<\/jats:sup>\n ) and\n \n B.\u00a0virosa<\/jats:italic>\n <\/jats:styled-content>\n (SCC\u00a0=\u00a00.17,\n P<\/jats:italic>\n \u00a0=\u00a02.4\u00a0\u00d7\u00a010\n \u22124<\/jats:sup>\n )]. One\u2010sample MR results showed a causal effect between gut microbial synthesis of the SCFA butyrate and appendicular lean mass (\n \u03b2<\/jats:italic>\n \u00a0=\u00a00.04, 95% confidence interval 0.029 to 0.051,\n P<\/jats:italic>\n \u00a0=\u00a00.003). Two\u2010sample MR results further confirmed the causal effect between gut microbial synthesis of the SCFA butyrate and appendicular lean mass (\n \u03b2<\/jats:italic>\n \u00a0=\u00a00.06, 95% confidence interval 0 to 0.13,\n P<\/jats:italic>\n \u00a0=\u00a00.06).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Our results may help the future development of novel intervention approaches for preventing or alleviating loss of SMM.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jcsm.12788","type":"journal-article","created":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T23:26:42Z","timestamp":1630538802000},"page":"1860-1870","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":146,"title":["Human gut microbiome impacts skeletal muscle mass via gut microbial synthesis of the short\u2010chain fatty acid butyrate among healthy menopausal women"],"prefix":"10.1002","volume":"12","author":[{"given":"Wan\u2010Qiang","family":"Lv","sequence":"first","affiliation":[{"name":"Center for System Biology, Data Sciences, and Reproductive Health, School of Basic Medical Science Central South University Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism The Third Affiliated Hospital of Southern Medical University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Shen","sequence":"additional","affiliation":[{"name":"Tulane Center of Biomedical Informatics and Genomics, Deming Department of Medicine Tulane University School of Medicine New Orleans LA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui\u2010Min","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for System Biology, Data Sciences, and Reproductive Health, School of Basic Medical Science Central South University Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Qiu","sequence":"additional","affiliation":[{"name":"Center for System Biology, Data Sciences, and Reproductive Health, School of Basic Medical Science Central South University Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo\u2010Yang","family":"Li","sequence":"additional","affiliation":[{"name":"Center for System Biology, Data Sciences, and Reproductive Health, School of Basic Medical Science Central South University Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Di","family":"Shen","sequence":"additional","affiliation":[{"name":"Center for System Biology, Data Sciences, and Reproductive Health, School of Basic Medical Science Central South University Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang\u2010Li","family":"Ge","sequence":"additional","affiliation":[{"name":"LC\u2010Bio Technologies Co., Ltd. Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng\u2010Ye","family":"Lv","sequence":"additional","affiliation":[{"name":"LC\u2010Bio Technologies Co., Ltd. Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism The Third Affiliated Hospital of Southern Medical University Guangzhou China"},{"name":"Shunde Hospital of Southern Medical University (The First People's Hospital of Shunde) Foshan Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong\u2010Mei","family":"Xiao","sequence":"additional","affiliation":[{"name":"Center for System Biology, Data Sciences, and Reproductive Health, School of Basic Medical Science Central South University Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7782-2956","authenticated-orcid":false,"given":"Hong\u2010Wen","family":"Deng","sequence":"additional","affiliation":[{"name":"Center for System Biology, Data Sciences, and Reproductive Health, School of Basic Medical Science Central South University Changsha Hunan China"},{"name":"Tulane Center of Biomedical Informatics and Genomics, Deming Department of Medicine Tulane University School of Medicine New Orleans LA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwh058"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1532-5415.2002.50216.x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.4027"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamda.2018.09.011"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aan5662"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17060932"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11053"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu328"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-019-0350-x"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-020-0743-8"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-018-0479-3"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgab146"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00031-7"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-018-0064-z"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0785-8"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.34408"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21758"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyv080"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21965"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0099-7"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.68.10.5186-5190.2002"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00889-14"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.62.5.1589-1592.1996"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0097342"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0705070104"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2009.01514.x"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/1462-2920.13589"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-06831-7"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1249\/MSS.0000000000001448"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature25973"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.13527"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmm020"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.maturitas.2011.01.014"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2939"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.03.014"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.03.004"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aam9949"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19082418"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00521.2018"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01780-14"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1017\/jns.2017.52"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5FO00886G"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu11071565"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12501"}],"container-title":["Journal 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