Paul C Okoro, Eric S Orwoll, Curtis Huttenhower, Xochitl Morgan, Thomas M Kuntz, Lauren J McIver, Alyssa B Dufour, Mary L Bouxsein, Lisa Langsetmo, Samaneh Farsijani, Deborah M Kado, Roberto Pacifici, Shivani Sahni, Douglas P Kiel
Journal: Frontiers in endocrinology 2023;14():1237727
PMID: 37810879
The gut microbiome can affect inflammation via T-cells, immune cells that play a role in immune and inflammation signalling and exert influence over bone loss. To date, there is limited data on how the gut microbiome impacts skeletal health. Hence, this study aimed to get a better picture of the human microbiome and how it relates to bone density, structure, and strength. The study involved data from 1227 participants from the Framingham Heart Study (FHS) and the Osteoporosis in Men Study (MrOS). Participants from the FHS were mixed genders, aged 32-89; whereas the MrOS participants were male only, aged 78-98. Stool samples were analyzed through gene sequencing to identify microbial species and various bone measures were obtained via scans. The study identified considerable associations between microbial groups and bone health in the FHS subjects. For example, higher levels of Akkermansia and Clostridiales were associated with lower bone density, while Lachnospiraceae and Faecalibacterium were linked to higher bone density. In the MrOS subjects, fewer associations of significance were found, suggesting that demographic factors like age and sex may influence the gut microbiome's impact on bone health. Even though the overall makeup of the microbiota composition appeared largely the same in both trials, there were notable variations in certain specific types of bacteria. The researchers discussed various metabolic pathways relating to the outcomes in bone health, but consistent findings were not observed across cohorts. In conclusion, the findings suggest a distinct link between the gut microbiome and skeletal metabolism yet further investigations into the mechanisms involved are needed.
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 - 89]), and the Osteoporosis in Men Study (MrOS [n=836, age range: 78 - 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] ≤ 0.1) including the association of with bone measures, which was independently replicated in the two cohorts. A meta-analysis of the taxa-bone associations further revealed (FDR ≤ 0.25) that greater abundances of the genera; and , were associated with lower radius total vBMD, and tibia cortical vBMD respectively. Conversely, higher abundances of the genera; , and 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.
Copyright © 2023 Okoro, Orwoll, Huttenhower, Morgan, Kuntz, McIver, Dufour, Bouxsein, Langsetmo, Farsijani, Kado, Pacifici, Sahni and Kiel.
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