{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T02:18:42Z","timestamp":1794277122775,"version":"4.9.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T00:00:00Z","timestamp":1695254400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, R01 AG066671, UL1 TR002369, HHSN268201500001I, N01-HC 25195, R01HL131015, K01 AG071855, R01 AR061445, P30AG024827"],"award-info":[{"award-number":["U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, R01 AG066671, UL1 TR002369, HHSN268201500001I, N01-HC 25195, R01HL131015, K01 AG071855, R01 AR061445, P30AG024827"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>\n                    The gut microbiome affects the inflammatory environment through effects on T-cells, which influence the production of immune mediators and inflammatory cytokines that stimulate osteoclastogenesis and bone loss in mice. However, there are few large human studies of the gut microbiome and skeletal health. We investigated the association between the human gut microbiome and high resolution peripheral quantitative computed tomography (HR-pQCT) scans of the radius and tibia in two large cohorts; Framingham Heart Study (FHS [n=1227, age range: 32 \u2013 89]), and the Osteoporosis in Men Study (MrOS [n=836, age range: 78 \u2013 98]). Stool samples from study participants underwent amplification and sequencing of the V4 hypervariable region of the 16S rRNA gene. The resulting 16S rRNA sequencing data were processed separately for each cohort, with the DADA2 pipeline incorporated in the16S bioBakery workflow. Resulting amplicon sequence variants were assigned taxonomies using the SILVA reference database. Controlling for multiple covariates, we tested for associations between microbial taxa abundances and HR-pQCT measures using general linear models as implemented in microbiome multivariable association with linear model (MaAslin2). Abundance of 37 microbial genera in FHS, and 4 genera in MrOS, were associated with various skeletal measures (false discovery rate [FDR] \u2264 0.1) including the association of\n                    <jats:italic>DTU089<\/jats:italic>\n                    with bone measures, which was independently replicated in the two cohorts. A meta-analysis of the taxa-bone associations further revealed (FDR \u2264 0.25) that greater abundances of the genera;\n                    <jats:italic>Akkermansia<\/jats:italic>\n                    and\n                    <jats:italic>DTU089<\/jats:italic>\n                    , were associated with lower radius total vBMD, and tibia cortical vBMD respectively. Conversely, higher abundances of the genera;\n                    <jats:italic>Lachnospiraceae NK4A136 group<\/jats:italic>\n                    , and\n                    <jats:italic>Faecalibacterium<\/jats:italic>\n                    were associated with greater tibia cortical vBMD. We also investigated functional capabilities of microbial taxa by testing for associations between predicted (based on 16S rRNA amplicon sequence data) metabolic pathways abundance and bone phenotypes in each cohort. While there were no concordant functional associations observed in both cohorts, a meta-analysis revealed 8 pathways including the super-pathway of histidine, purine, and pyrimidine biosynthesis, associated with bone measures of the tibia cortical compartment. In conclusion, our findings suggest that there is a link between the gut microbiome and skeletal metabolism.\n                  <\/jats:p>","DOI":"10.3389\/fendo.2023.1237727","type":"journal-article","created":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T08:30:01Z","timestamp":1695457801000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":36,"title":["A two-cohort study on the association between the gut microbiota and bone density, microarchitecture, and strength"],"prefix":"10.3389","volume":"14","author":[{"given":"Paul C.","family":"Okoro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric 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