A Relationship Between the Gut Microbiome and Bone Density

Changes in the gut microbiome take place with advancing age, an increase in populations that provoke chronic inflammation, a reduction in the populations producing beneficial metabolites. Even only considering rising levels of inflammation in the aging body, it is clear that the gut microbiome can contribute to many age-related conditions. As researchers investigate the details, they also find other ways in which specific manifestations of aging may be in part caused by changes in the gut microbiome. Given that there are practical approaches demonstrated to restore a more youthful balance of intestinal microbial populations, such as flagellin immunization and fecal microbiota transplantation, one would imagine that we'll see greater adoption of these interventions in the near future.

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=1,227, 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 16S rRNA gene. The resulting 16S rRNA sequencing data was processed separately for each cohort. 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. Abundance of 37 microbial genera in FHS, and 4 genera in MrOS, were associated with various skeletal measures including the association of DTU089 with bone measures, which was independently replicated in the two cohorts.

A meta-analysis of the taxa-bone associations further revealed that greater abundances of the genera; Akkermansia and DTU089, were associated with lower radius total volumetric bone mineral density (vBDM), and tibia cortical vBMD respectively. Conversely, higher abundances of the genera; Lachnospiraceae NK4A136 group, and Faecalibacterium 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.

Link: https://doi.org/10.3389/fendo.2023.1237727