{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:23:03Z","timestamp":1790716983771,"version":"4.1.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"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. Nutr."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Osteoporosis (OP) is a multifactorial skeletal disorder influenced by host metabolism, inflammation, and gut microbiota-derived metabolites such as S-equol. However, the interplay between intestinal microbiota, S-equol production, and host metabolic profiles in OP remains incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To conduct a preliminary multi-omics investigation integrating metagenomic and metabolomic analyses to identify gut microbiota and metabolite biomarkers associated with serum S-equol levels in older adults with OP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A cross-sectional study was conducted in 39 community-dwelling adults aged \u226550\u202fyears in Haikou, China. Participants were grouped into OP and control groups based on lumbar spine T-scores, using a cut-off value of \u2264\u202f\u2212\u202f2.5 to define osteoporosis. Serum biomarkers (S-equol, inflammatory cytokines, oxidative stress indicators) were assessed by ELISA. Fecal samples underwent metagenomic sequencing and untargeted metabolomics. LEfSe, Spearman correlation, machine learning, and KEGG enrichment were used to explore microbiota-metabolite-bone health axes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Serum S-equol levels were significantly lower in the OP group compared to controls (3,561\u202f\u00b1\u202f304 vs. 3,855\u202f\u00b1\u202f469\u202fpg\/mL,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.026), whereas most inflammatory markers were comparable between groups, apart from a modest increase in IL-1\n                      <jats:italic>\u03b2<\/jats:italic>\n                      in OP. Metagenomic analysis revealed a lower relative abundances of key SCFA-producing taxa in OP (e.g.,\n                      <jats:italic>Faecalibacterium prausnitzii<\/jats:italic>\n                      ,\n                      <jats:italic>Roseburia hominis<\/jats:italic>\n                      ,\n                      <jats:italic>Bacteroides uniformis<\/jats:italic>\n                      ). Metabolomic profiling identified distinct alterations in amino acid and tryptophan pathways, with KEGG analysis highlighting disruptions in glycerophospholipid, glycine-serine\u2013threonine, and choline metabolism. Discriminative metabolites (e.g., Gln-Val-Ile-Asp., 5-oxooctanoic acid) showed diagnostic potential (AUC\u202f&amp;gt;\u202f0.75). S-equol levels positively correlated with these beneficial microbes and with amino acid-related metabolites (e.g., D-tryptophan, 3-indoleacrylic acid, N-methylglutamate). Network and heatmap analyses illustrated differences in microbial-metabolite association patterns between groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In conclusion, low levels of serum S-equol in older adults with osteoporosis were associated with distinct changes in gut microbiota composition and fecal metabolic profiles in this pilot study.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnut.2026.1784894","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T06:57:04Z","timestamp":1771397824000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Exploratory multi-omics analysis of gut microbiota and fecal metabolites in relation to serum S-equol levels in older adults with osteoporosis from a tropical community: a pilot study"],"prefix":"10.3389","volume":"13","author":[{"given":"Wenting","family":"Cao","sequence":"first","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Public Health, Hainan Academy of Medical Sciences, Hainan Medical University","place":["Haikou, Hainan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Public Health, Hainan Academy of Medical Sciences, Hainan Medical University","place":["Haikou, Hainan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanxiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Public Health, Hainan Academy of Medical Sciences, Hainan Medical University","place":["Haikou, Hainan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianxia","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Public Health, Hainan Academy of Medical Sciences, Hainan Medical University","place":["Haikou, Hainan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxin","family":"Pan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Public Health, Hainan Academy of Medical Sciences, Hainan Medical University","place":["Haikou, Hainan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, First Affiliated Hospital of Hainan Medical University","place":["Haikou, Hainan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingqi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Diagnosis, Fifth Affiliated Hospital of Harbin Medical University","place":["Daqing, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiashu","family":"Ke","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Public Health, Hainan Academy of Medical Sciences, Hainan Medical University","place":["Haikou, Hainan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jindong Ding","family":"Petersen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Public Health, Hainan Academy of Medical Sciences, Hainan Medical University","place":["Haikou, Hainan, China"]},{"name":"Department of Public Health, University of Copenhagen","place":["Copenhagen, Denmark"]},{"name":"Department of Public Health, University of Southern Denmark","place":["Odense, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Public Health, Hainan Academy of Medical Sciences, Hainan Medical University","place":["Haikou, Hainan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"04009","DOI":"10.7189\/jogh.15.04009","article-title":"Prevalence of osteoporosis and associated factors among Chinese adults: a systematic review and modelling study","volume":"15","author":"Liu","year":"2025","journal-title":"J Glob 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