{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T21:24:59Z","timestamp":1775856299114,"version":"3.50.1"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"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. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Postmenopausal osteoporosis (PMO), a prevalent bone disease triggered by estrogen deficiency - induced bone mass reduction and deterioration of bone tissue microarchitecture, escalates the risk of fragility fractures. Recent research has highlighted the pivotal role of oral and gut microbiota in PMO development, giving rise to the \u201coral - gut - bone axis\u201d concept.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 21 postmenopausal women, aged 50 - 60, were recruited for the study. Based on bone mineral density (BMD) measurements from dual - energy X - ray absorptiometry (DXA), participants were divided into osteopenia, osteoporosis, and healthy groups. Saliva and dental plaque samples were collected for metagenomic sequencing to analyze microbial diversity and community composition, with differences identified via LEfSe analysis. KEGG pathway analysis was used to reveal variations in microbial functions. Based on these analyses, predictive models for bone density status were constructed using LASSO regression and random forest algorithms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Significant differences in salivary microbial community structures were found between the osteoporosis and healthy groups (P = 0.041). LEfSe analysis revealed higher abundance of Aggregatibacter, Haemophilus haemolyticus, Haemophilus sputorum, Pasteurellaceae, Neisseria elongata, Aggregatibacter segnis, and Aggregatibacter aphrophilus in the osteopenia group, and higher abundance of Streptococcus pneumoniae and Haemophilus paraphrohaemolyticus in the osteoporosis group compared to the healthy group. The random forest models for osteopenia vs. healthy and osteoporosis vs. healthy yielded AUC values of 0.82 and 0.74, respectively, suggesting potential predictive capability, though further validation in larger cohorts is needed to confirm their generalizability. Functional analysis using LEfSe identified differential KEGG pathways, including glycan biosynthesis and metabolism in cancer, choline metabolism in cancer, and the cGMP-PKG signaling pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This exploratory study utilized metagenomic sequencing to analyze the relationship between oral microbiota and PMO while controlling for key confounders. We identified significant compositional and functional alterations in the oral microbiome associated with bone mineral density status, including specific bacterial species showing marked intergroup differences. A model based on differential microbial features exhibited preliminary discriminative capacity, and functional analysis suggested involvement of inflammatory and metabolic pathways. These findings provide initial evidence linking oral microbiota to PMO.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2025.1663645","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T06:25:56Z","timestamp":1764570356000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Correlation between oral microbial characteristics and overall bone density of Postmenopausal women based on macrogenomic analysis"],"prefix":"10.3389","volume":"15","author":[{"given":"Man","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongjun","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhifeng","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chanjuan","family":"Ye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xixi","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiuying","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dali","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youguang","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e22171","DOI":"10.7759\/cureus.22171","article-title":"Association between osteoporosis and refracture rate among patients with hip fractures at king abdulaziz medical city, Saudi Arabia","volume":"14","author":"AlYami","year":"2022","journal-title":"Cureus"},{"key":"B2","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1126\/science.aan4526","article-title":"Ectopic colonization of oral bacteria in the intestine drives TH1 cell induction and inflammation","volume":"358","author":"Atarashi","year":"2017","journal-title":"Science"},{"key":"B3","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1038\/s41368-022-00183-3","article-title":"Periodontitis may induce gut microbiota dysbiosis via salivary microbiota","volume":"14","author":"Bao","year":"2022","journal-title":"Int. J. Oral. Sci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.jhep.2014.04.001","article-title":"Risk of hip fracture associated with untreated and treated chronic hepatitis B virus infection","volume":"61","author":"Byrne","year":"2014","journal-title":"J. Hepatol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"17126","DOI":"10.1038\/s41598-018-35473-6","article-title":"Variations in oral microbiome profiles in rheumatoid arthritis and osteoarthritis with potential biomarkers for arthritis screening","volume":"8","author":"Chen","year":"2018","journal-title":"Sci. Rep."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.751503","article-title":"Oral osteomicrobiology: the role of oral microbiota in alveolar bone homeostasis","volume":"11","author":"Cheng","year":"2021","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nature13178","article-title":"Dynamics and associations of microbial community types across the human body","volume":"509","author":"Ding","year":"2014","journal-title":"Nature"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.26599\/FSHW.2022.9250001","article-title":"Targeting gut microbiota in osteoporosis: impact of the microbial-based functional food ingredients","volume":"13","author":"Duffuler","year":"2024","journal-title":"Food Sci. Hum. Wellness."},{"key":"B9","doi-asserted-by":"publisher","first-page":"4632","DOI":"10.1210\/jc.2014-2222","article-title":"Associations of the fecal microbiome with urinary estrogens and estrogen metabolites in postmenopausal women","volume":"99","author":"Fuhrman","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"B10","doi-asserted-by":"publisher","first-page":"8583","DOI":"10.18632\/aging.103168","article-title":"Gut microbiota and metabolite alterations associated with reduced bone mineral density or bone metabolic indexes in postmenopausal osteoporosis","volume":"12","author":"He","year":"2020","journal-title":"Aging (Albany NY)."},{"key":"B11","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1159\/000541999","article-title":"Gut microbiota-bone axis","volume":"81","author":"Indrio","year":"2025","journal-title":"Ann. Nutr. Metab."},{"key":"B12","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1111\/jre.12248","article-title":"Bacterial invasion and persistence: critical events in the pathogenesis of periodontitis","volume":"50","author":"Ji","year":"2015","journal-title":"J. Periodontal. Res."},{"key":"B13","doi-asserted-by":"publisher","first-page":"297","DOI":"10.20524\/aog.2016.0037","article-title":"Vitamin D deficiency in patients with liver cirrhosis","volume":"29","author":"Konstantakis","year":"2016","journal-title":"Ann. Gastroenterol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1038\/s41579-024-01075-5","article-title":"The oral-gut microbiome axis in health and disease","volume":"22","author":"Kunath","year":"2024","journal-title":"Nat. Rev. Microbiol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"9348","DOI":"10.18632\/aging.102376","article-title":"Fructus Ligustri Lucidi preserves bone quality through the regulation of gut microbiota diversity, oxidative stress, TMAO and Sirt6 levels in aging mice","volume":"11","author":"Li","year":"2019","journal-title":"Aging"},{"key":"B16","doi-asserted-by":"publisher","first-page":"10633","DOI":"10.18632\/aging.103283","article-title":"Gut microbiota-dependent Trimethylamine N-Oxide are related with hip fracture in postmenopausal women: a matched case-control study","volume":"12","author":"Liu","year":"2020","journal-title":"Aging (Albany NY)."},{"key":"B17","doi-asserted-by":"publisher","first-page":"e23","DOI":"10.1002\/imt2.23","article-title":"The sampling strategy of oral microbiome","volume":"1","author":"Lu","year":"2022","journal-title":"Imeta"},{"key":"B18","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1186\/s12891-024-07904-1","article-title":"Osteoporosis in postmenopausal women is associated with disturbances in gut microbiota and migration of peripheral immune cells","volume":"25","author":"Ma","year":"2024","journal-title":"BMC Musculoskelet. Disord."},{"key":"B19","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1111\/joim.12805","article-title":"Lactobacillus reuteri reduces bone loss in older women with low bone mineral density: a randomized, placebo-controlled, double-blind, clinical trial","volume":"284","author":"Nilsson","year":"2018","journal-title":"J. Intern. Med."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms8111630","article-title":"A multi-omic analysis for low bone mineral density in postmenopausal women suggests a RELATIONSHIP between diet, metabolites, and microbiota","volume":"8","author":"Palacios-Gonz\u00e1lez","year":"2020","journal-title":"Microorganisms"},{"key":"B21","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1186\/s12903-023-02990-4","article-title":"Association between periodontitis and osteoporosis in United States adults from the National Health and Nutrition Examination Survey: a cross-sectional analysis","volume":"23","author":"Peng","year":"2023","journal-title":"BMC Oral. Health"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3390\/medicina59091546","article-title":"From cells to environment: exploring the interplay between factors shaping bone health and disease","volume":"59","author":"Singh","year":"2023","journal-title":"Med. (Kaunas)."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1667","DOI":"10.2147\/JIR.S351918","article-title":"The rising era of \u201cImmunoporosis\u201d: role of immune system in the pathophysiology of osteoporosis","volume":"15","author":"Srivastava","year":"2022","journal-title":"J. Inflammation Res."},{"key":"B24","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1002\/jbmr.2765","article-title":"The microbiome and musculoskeletal conditions of aging: A review of evidence for impact and potential therapeutics","volume":"31","author":"Steves","year":"2016","journal-title":"J. Bone Miner. Res."},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1289452","article-title":"The oral-gut-circulatory axis: from homeostasis to colon cancer","volume":"13","author":"Tortora","year":"2023","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3390\/nu12113432","article-title":"Kefir peptides prevent estrogen deficiency-induced bone loss and modulate the structure of the gut microbiota in ovariectomized mice","volume":"12","author":"Tu","year":"2020","journal-title":"Nutrients"},{"key":"B27","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1146\/annurev-pathmechdis-031521-040919","article-title":"Osteoclasts, master sculptors of bone","volume":"18","author":"Veis","year":"2023","journal-title":"Annu. Rev. Pathol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1038\/s41368-018-0018-x","article-title":"The oral microbiome bank of China","volume":"10","author":"Xian","year":"2018","journal-title":"Int. J. Oral. Sci."},{"key":"B29","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.jdsr.2023.08.003","article-title":"Oral-gut axis as a novel biological mechanism linking periodontal disease and systemic diseases: A review","volume":"59","author":"Yamazaki","year":"2023","journal-title":"Jpn. Dent. Sci. Rev."},{"key":"B30","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.mucimm.2023.11.006","article-title":"Exploring the oral-gut linkage: Interrelationship between oral and systemic diseases","volume":"17","author":"Yamazaki","year":"2024","journal-title":"Mucosal Immunol."},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.930244","article-title":"Changes in the composition of gut and vaginal microbiota in patients with postmenopausal osteoporosis","volume":"13","author":"Yang","year":"2022","journal-title":"Front. Immunol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"159","DOI":"10.11622\/smedj.2021036","article-title":"Menopausal osteoporosis: screening, prevention and treatment","volume":"62","author":"Yong","year":"2021","journal-title":"Singapore. Med. J."},{"key":"B33","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1111\/prd.12422","article-title":"Osteoporosis and periodontal diseases - An update on their association and mechanistic links","volume":"89","author":"Yu","year":"2022","journal-title":"Periodontol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"542","DOI":"10.26355\/eurrev_202401_35052","article-title":"Causal link between gut microbiota and osteoporosis analyzed via Mendelian randomization","volume":"28","author":"Zeng","year":"2024","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1610","DOI":"10.4314\/ahs.v20i4.13","article-title":"Association between osteoporosis and hepatitis B cirrhosis: a case-control study","volume":"20","author":"Zhang","year":"2020","journal-title":"Afr. Health Sci."},{"key":"B36","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1007\/s11596-020-2243-8","article-title":"Effect of periodontal pathogens on total bone volume fraction: A phenotypic study","volume":"40","author":"Zhang","year":"2020","journal-title":"Curr. Med. Sci."},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.993253","article-title":"Application of metabolomics in osteoporosis research","volume":"13","author":"Zhao","year":"2022","journal-title":"Front. Endocrinol. (Lausanne)."},{"key":"B38","doi-asserted-by":"publisher","first-page":"9251","DOI":"10.18632\/aging.205869","article-title":"Trimethylamine-N-oxide promotes osteoclast differentiation and oxidative stress by activating NF-\u03baB pathway","volume":"16","author":"Zhao","year":"2024","journal-title":"Aging (Albany NY)."},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.774257","article-title":"Association of antibiotic alterations in gut microbiota with decreased osseointegration of an intramedullary nail in mice with and without osteomyelitis","volume":"12","author":"Zhao","year":"2021","journal-title":"Front. Endocrinol. (Lausanne)."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1663645\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T06:25:57Z","timestamp":1764570357000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1663645\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,1]]},"references-count":39,"alternative-id":["10.3389\/fcimb.2025.1663645"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2025.1663645","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,1]]},"article-number":"1663645"}}