Gut microbiota is associated with bone mineral density : an observational and genome-wide environmental interaction analysis in the UK Biobank cohort.

Aims: Despite the interest in the association of gut microbiota with bone health, limited population-based studies of gut microbiota and bone mineral density (BMD) have been made. Our aim is to explore the possible association between gut microbiota and BMD.
Methods: A total of 3,321 independent loci of gut microbiota were used to calculate the individual polygenic risk score (PRS) for 114 gut microbiota-related traits. The individual genotype data were obtained from UK Biobank cohort. Linear regressions were then conducted to evaluate the possible association of gut microbiota with L1-L4 BMD (n = 4,070), total BMD (n = 4,056), and femur total BMD (n = 4,054), respectively. PLINK 2.0 was used to detect the single-nucleotide polymorphism (SNP) × gut microbiota interaction effect on the risks of L1-L4 BMD, total BMD, and femur total BMD, respectively.
Results: We detected five, three, and seven candidate gut microbiota-related traits for L1-L4 BMD, total BMD, and femur BMD, respectively, such as genus Dialister (p = 0.004) for L1-L4 BMD, and genus Eisenbergiella (p = 0.046) for total BMD. We also detected two common gut microbiota-related traits shared by L1-L4 BMD, total BMD, and femur total BMD, including genus Escherichia Shigella and genus Lactococcus . Interaction analysis of BMD detected several genes that interacted with gut microbiota, such as phospholipase D1 ( PLD1 ) and endomucin ( EMCN ) interacting with genus Dialister in total BMD, and COL12A1 and Discs Large MAGUK Scaffold Protein 2 ( DLG2 ) interacting with genus Lactococcus in femur BMD.
Conclusion: Our results suggest associations between gut microbiota and BMD, which will be helpful to further explore the regulation mechanism and intervention gut microbiota of BMD. Cite this article: Bone Joint Res  2021;10(11):734-741.