{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T18:09:34Z","timestamp":1788890974643,"version":"build-2803163510"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Postmenopausal bone loss is a multifactorial condition influenced by hormonal changes, metabolic dysregulation, and gut microbiota alterations. Emerging evidence indicates the potential significance of the gut microbiota-bone link in maintaining bone homeostasis. The present study investigated the composition of the gut microbiota and serum metabolite signatures of postmenopausal women afflicted with bone loss, as well as the interrelationships between these factors, to explore the potential associations of the gut microbiota-bone link.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      In total, 105 postmenopausal women from Beijing were classified by DXA into a bone loss group (L1\u2013L4\n                      <jats:italic>T<\/jats:italic>\n                      -score &amp;lt;\u22121.0;\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f58) and a normal bone mass group (L1\u2013L4\n                      <jats:italic>T<\/jats:italic>\n                      -score \u2265\u22121.0;\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f47). Gut microbiota composition was assessed by 16S rRNA sequencing and serum metabolites by UHPLC-MS\/MS. Differential abundance and Spearman correlation analyses were performed in relation to BMD\/\n                      <jats:italic>T<\/jats:italic>\n                      -scores and serum biochemical indicators.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compared with controls, the bone-loss cohort showed lower BMD and\n                      <jats:italic>T<\/jats:italic>\n                      -scores at L1\u2013L4 and at the femoral neck, and a longer period since menopause. Additionally, the bone-loss cohort exhibited modestly higher, yet still subnormal, circulating 25(OH)D and 25(OH)D3 concentrations, which were inversely associated with L1\u2013L4\n                      <jats:italic>T<\/jats:italic>\n                      -scores. The bone loss group was characterized by a diminished abundance of protective genera\n                      <jats:italic>Prevotella<\/jats:italic>\n                      and\n                      <jats:italic>Dorea<\/jats:italic>\n                      and increased levels of Limosilactobacillus and Olsenella. Prevotella and Dorea showed positive trends with L1\u2013L4\n                      <jats:italic>T<\/jats:italic>\n                      -scores but did not reach statistical significance. Metabolomic analysis identified 33 differential metabolites, with higher levels of flavonoids (taxifolin), L-arginine, and spermidine in the normal bone group and reduced lysophosphatidylcholine levels. N-acetylanthranilic acid (NAA) was positively correlated with L1\u2013L4\n                      <jats:italic>T<\/jats:italic>\n                      -scores and the relative abundances of Prevotella and Dorea.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Postmenopausal bone loss is associated with gut microbiota alterations and altered serum metabolic profiles. Although circulating 25(OH)D levels were relatively higher (yet still subnormal) in the bone-loss group, this cross-sectional observation should be interpreted as an association rather than evidence of a compensatory mechanism. Our findings indicate that NAA and its associated taxa are correlationally associated with bone-related phenotypes, supporting a testable microbiota-metabolite hypothesis that warrants validation in longitudinal or interventional studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1750495","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T07:01:26Z","timestamp":1772607686000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Altered gut microbiota and serum metabolite profiles characterize postmenopausal bone loss: insights into the gut-bone axis"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhiming","family":"Guan","sequence":"first","affiliation":[{"name":"School of Public Health, Shandong Second Medical University","place":["Weifang, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanpin","family":"Liu","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Dairy Health for Maternal and Child, Beijing Sanyuan Foods Co. Ltd.","place":["Beijing, China"]},{"name":"Beijing Engineering Research Center of Dairy, Beijing Technical Innovation Center of Human Milk Research, Beijing Sanyuan Foods Co. Ltd.","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junying","family":"Zhao","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Dairy Health for Maternal and Child, Beijing Sanyuan Foods Co. Ltd.","place":["Beijing, China"]},{"name":"Beijing Engineering Research Center of Dairy, Beijing Technical Innovation Center of Human Milk Research, Beijing Sanyuan Foods Co. Ltd.","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longlong","family":"Jia","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Dairy Health for Maternal and Child, Beijing Sanyuan Foods Co. Ltd.","place":["Beijing, China"]},{"name":"Beijing Engineering Research Center of Dairy, Beijing Technical Innovation Center of Human Milk Research, Beijing Sanyuan Foods Co. Ltd.","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Public Health, Shandong Second Medical University","place":["Weifang, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Pan","sequence":"additional","affiliation":[{"name":"School of Public Health, Shandong Second Medical University","place":["Weifang, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Chen","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Dairy Health for Maternal and Child, Beijing Sanyuan Foods Co. Ltd.","place":["Beijing, China"]},{"name":"Beijing Engineering Research Center of Dairy, Beijing Technical Innovation Center of Human Milk Research, Beijing Sanyuan Foods Co. Ltd.","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,4]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1007\/s43465-023-01012-3","article-title":"Epidemiology of osteoporosis","volume":"57","author":"Agrawal","year":"2023","journal-title":"Indian J. Orthop."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1007\/s10875-010-9507-1","article-title":"Leptin activates human B cells to secrete TNF-\u03b1, IL-6 and IL-10 via JAK2\/STAT3 and p38MAPK\/ERK1\/2 signaling pathway","volume":"31","author":"Agrawal","year":"2011","journal-title":"J. Clin. Immunol."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1302\/2046-3758.1012.BJR-2021-0452.R1","article-title":"Osteoporosis: current screening methods, novel techniques, and preoperative assessment of bone mineral density","volume":"10","author":"Al-Hourani","year":"2021","journal-title":"Bone. Joint. Res."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"16","DOI":"10.3390\/biomedicines10010016","article-title":"Characterization of the gut microbiota in individuals with overweight or obesity during a real-world weight loss dietary program: a focus on the Bacteroides 2 enterotype","volume":"10","author":"Alili","year":"2022","journal-title":"Biomedicines"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1007\/s11914-017-0394-8","article-title":"Vitamin D activity and metabolism in bone","volume":"15","author":"Anderson","year":"2017","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.30565\/medalanya.1076252","article-title":"Osteoporosis and fragilty fractures: an overview","volume":"6","author":"Aslan","year":"2022","journal-title":"Acta Med. Alanya"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"3809","DOI":"10.1016\/j.tjnut.2025.08.034","article-title":"Microbiota-dependent fiber responses: a proof-of-concept study on short-chain fatty acid production in Prevotella- and Bacteroides-dominated healthy individuals","volume":"155","author":"Bartsch","year":"2025","journal-title":"J. Nutr."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"112299","DOI":"10.1016\/j.celrep.2023.112299","article-title":"Specific host metabolite and gut microbiome alterations are associated with bone loss during spaceflight","volume":"42","author":"Bedree","year":"2023","journal-title":"Cell Rep."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1038\/s41575-025-01092-6","article-title":"Intestinal pH: a major driver of human gut microbiota composition and metabolism","volume":"22","author":"Brinck","year":"2025","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1002\/jcp.1041530321","article-title":"Effect of membrane phosphatidylethanolamine-deficiency\/phosphatidylcholine-excess on metabolism of phosphatidylcholine and phosphatidylethanolamine","volume":"153","author":"Fisk","year":"1992","journal-title":"J. Cell. Physiol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1638","DOI":"10.1002\/jbmr.2887","article-title":"Links between the microbiome and bone","volume":"31","author":"Hernandez","year":"2016","journal-title":"J. Bone Miner. Res."},{"key":"ref12","first-page":"797","article-title":"Epidemiology of osteoporosis in Japan","volume":"22","author":"Iki","year":"2012","journal-title":"Clin. Calcium"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"4639","DOI":"10.4049\/jimmunol.1600822","article-title":"The nuclear receptor AhR controls bone homeostasis by regulating osteoclast differentiation via the RANK\/c-Fos signaling axis","volume":"197","author":"Izawa","year":"2016","journal-title":"J. Immunol."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1007\/s40520-018-1109-4","article-title":"Executive summary of European guidance for the diagnosis and management of osteoporosis in postmenopausal women","volume":"31","author":"Kanis","year":"2019","journal-title":"Aging Clin. Exp. Res."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1007\/s00018-018-2981-y","article-title":"Coupling factors involved in preserving bone balance","volume":"76","author":"Kim","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1210\/ER.2017-00064","article-title":"Energy metabolism of the osteoblast: implications for osteoporosis","volume":"38","author":"Lee","year":"2017","journal-title":"Endocr. Rev."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"90","DOI":"10.3803\/EnM.2013.28.2.90","article-title":"Epidemiology of osteoporosis and osteoporotic fractures in South Korea","volume":"28","author":"Lee","year":"2013","journal-title":"Endocrinol. Metab."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.bcp.2016.03.002","article-title":"Anti-osteoclastogenic activity of isoliquiritigenin via inhibition of NF-\u03baB-dependent autophagic pathway","volume":"106","author":"Liu","year":"2016","journal-title":"Biochem. Pharmacol."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"109174","DOI":"10.1016\/j.isci.2024.109174","article-title":"NAD metabolic therapy in metabolic dysfunction-associated steatotic liver disease: possible roles of gut microbiota","volume":"27","author":"Lu","year":"2024","journal-title":"iScience"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1038\/s41413-023-00264-x","article-title":"Modulation of bone remodeling by the gut microbiota: a new therapy for osteoporosis","volume":"11","author":"Lyu","year":"2023","journal-title":"Bone Res."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1038\/s41574-024-01039-y","article-title":"Skeletal stem and progenitor cells in bone physiology, ageing and disease","volume":"21","author":"Melis","year":"2025","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref22","first-page":"1056","article-title":"Research study on relation between age and bone mineral density","author":"Muhan","year":"2022"},{"key":"ref1001","article-title":"Vegan: Community Ecology Package. R package version 2.8-0","author":"Oksanen","year":"2025"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"2294","DOI":"10.3390\/cells9102294","article-title":"The role of aryl-hydrocarbon receptor (AhR) in osteoclast differentiation and function","volume":"9","author":"Park","year":"2020","journal-title":"Cells"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1016\/0304-4165(71)90173-5","article-title":"N-acetylanthranilic acid biosynthesis in Aerobacter aerogenes and Escherichia coli","volume":"230","author":"Paul","year":"1971","journal-title":"Biochim. Biophys. Acta"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1080","DOI":"10.1016\/S0140-6736(21)02646-5","article-title":"Drug therapy for osteoporosis in older adults","volume":"399","author":"Reid","year":"2022","journal-title":"Lancet"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1002\/jbmr.5650100315","article-title":"Expression and functional role of nitric oxide synthase in osteoblast-like cells","volume":"10","author":"Riancho","year":"1995","journal-title":"J. Bone Miner. Res."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"936914","DOI":"10.3389\/fbioe.2022.936914","article-title":"Engineering the active site pocket to enhance the catalytic efficiency of a novel feruloyl esterase derived from human intestinal bacteria Dorea formicigenerans","volume":"10","author":"Shen","year":"2022","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"108168","DOI":"10.1016\/j.pharmthera.2022.108168","article-title":"Advances in pathogenesis and therapeutic strategies for osteoporosis","volume":"237","author":"Song","year":"2022","journal-title":"Pharmacol. Ther."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1124945","DOI":"10.3389\/fmicb.2023.1124945","article-title":"The associations of gut microbiota, endocrine system and bone metabolism","volume":"14","author":"Tu","year":"2023","journal-title":"Front. Microbiol."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1515\/CCLM.2011.602","article-title":"International Osteoporosis Foundation and International Federation of Clinical Chemistry and Laboratory Medicine position on bone marker standards in osteoporosis","volume":"49","author":"Vasikaran","year":"2011","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"603","DOI":"10.18203\/2319-2003.ijbcp20251847","article-title":"The rising global burden of osteoporosis: insights into prevalence, fracture rates, and future trends","volume":"14","author":"Vijayakumar","year":"2025","journal-title":"Int. J. Basic Clin. Pharmacol."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"1664","DOI":"10.1080\/10408398.2015.1010034","article-title":"Gut microbiota-bone axis","volume":"57","author":"Villa","year":"2017","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"2034","DOI":"10.1016\/j.bcp.2008.02.025","article-title":"Benzo[a]pyrene inhibits osteoclastogenesis by affecting RANKL-induced activation of NF-\u03baB","volume":"75","author":"Voronov","year":"2008","journal-title":"Biochem. Pharmacol."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"2081","DOI":"10.14336\/AD.2023.0425","article-title":"Association between dysbiosis in the gut microbiota of primary osteoporosis patients and bone loss","volume":"14","author":"Waldbaum","year":"2023","journal-title":"Aging Dis."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"1304","DOI":"10.1093\/ajcn\/nqab194","article-title":"An emerging role of Prevotella histicola on estrogen deficiency-induced bone loss through the gut microbiota-bone axis in postmenopausal women and in ovariectomized mice","volume":"114","author":"Wang","year":"2021","journal-title":"Am. J. Clin. Nutr."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"0728","DOI":"10.34133\/research.0728","article-title":"Aberrant tryptophan metabolism manipulates osteochondral homeostasis","volume":"8","author":"Xiang","year":"2025","journal-title":"Research"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"950","DOI":"10.3390\/microorganisms11040950","article-title":"The preventive effects of probiotic Prevotella histicola on the bone loss of mice with ovariectomy-mediated osteoporosis","volume":"11","author":"Zhang","year":"2023","journal-title":"Microorganisms"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1159\/000495254","article-title":"Taxifolin inhibits receptor activator of NF-\u03baB ligand-induced osteoclastogenesis of human bone marrow-derived macrophages in vitro and prevents lipopolysaccharide-induced bone loss in vivo","volume":"103","author":"Zhang","year":"2019","journal-title":"Pharmacology"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1016\/j.synbio.2025.05.001","article-title":"CgAS, a gene encoding anthranilic acid synthase, contributes to tryptophan biosynthesis and enhanced chaetoglobosin A production in Chaetomium globosum W7","volume":"10","author":"Zhao","year":"2025","journal-title":"Synth. Syst. Biotechnol."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1750495\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T07:01:30Z","timestamp":1772607690000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1750495\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,4]]},"references-count":40,"alternative-id":["10.3389\/fmicb.2026.1750495"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2026.1750495","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,4]]},"article-number":"1750495"}}