{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T09:26:06Z","timestamp":1780046766749,"version":"3.53.1"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T00:00:00Z","timestamp":1635811200000},"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:p><jats:bold>Objective:<\/jats:bold> This study aimed to explore the relationships between the common variants of R-spondin\/Wnt signaling genes, gut microbiota composition, and osteoporosis (OP) risk in elderly Chinese Han population.<\/jats:p><jats:p><jats:bold>Design:<\/jats:bold> Dual-energy X-ray absorptiometry was used to obtain the OP-associated measurements at multiple skeleton sites among all 1,168 participants. Genotyping data was obtained by using the next-generation sequencing in the discovery stage (<jats:italic>n<\/jats:italic> = 400, 228 OP patients) and SNPscan technology in the replication stage (<jats:italic>n<\/jats:italic> = 768, 356 OP patients). Bioinformatic analysis was performed to provide more evidence for the genotype-OP associations. The 16S ribosomal RNA gene high-throughput sequencing technology was adopted to explore OP-associated gut microbiota variations.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> The genetic variants of rs10920362 in the <jats:italic>LGR6<\/jats:italic> gene (<jats:italic>P<\/jats:italic>-FDR = 1.19 \u00d7 10<jats:sup>\u20136<\/jats:sup>) and rs11178860 in the <jats:italic>LGR5<\/jats:italic> gene (<jats:italic>P<\/jats:italic>-FDR = 1.51 \u00d7 10<jats:sup>\u20134<\/jats:sup>) were found to associate with OP risk significantly. Several microbial taxa were associated with the BMDs and T-scores at multiple skeleton sites. The associations between rs10920362 and BMD-associated microbiota maintained significance after adjusting confounders. The rs10920362 CT\/TT genotype associated with a decreased relative abundance of <jats:italic>Actinobacteria<\/jats:italic> (\u03b2 = \u22121.32, <jats:italic>P<\/jats:italic> &amp;lt; 0.001), <jats:italic>Bifidobacteriaceae<\/jats:italic> (\u03b2 = \u22121.70, <jats:italic>P<\/jats:italic> &amp;lt; 0.001), and <jats:italic>Bifidobacterium<\/jats:italic> (\u03b2 = \u22121.70, <jats:italic>P<\/jats:italic> &amp;lt; 0.001) compared to the CC genotype.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Our findings suggested that the variants loci of <jats:italic>LGR6<\/jats:italic> may be associate with OP pathogenesis via gut microbiota modifications. The relationship between host genetics and gut microbiome provides new perspectives about OP prevention and treatment.<\/jats:p>","DOI":"10.3389\/fmicb.2021.765008","type":"journal-article","created":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T06:34:37Z","timestamp":1635834877000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Integrative Analysis of LGR5\/6 Gene Variants, Gut Microbiota Composition and Osteoporosis Risk in Elderly Population"],"prefix":"10.3389","volume":"12","author":[{"given":"Dong-sheng","family":"Di","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mu-hong","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan-shan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-jing","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao-long","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru-yi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1007\/s00204-012-0988-y","article-title":"Endocrine disruptors and bone metabolism.","volume":"87","author":"Agas","year":"2013","journal-title":"Arch. 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