Investigating the link between gut microbiome and bone mineral density: The role of genetic factors

Osteoporosis is a complex metabolic bone disease that severely undermines the quality of life and overall health of the elderly. While previous studies have established a close relationship between gut microbiome and host bone metabolism, the role of genetic factors has received less scrutiny. This research aims to identify potential taxa associated with various bone mineral density states, incorporating assessments of genetic factors. Fecal microbiome profiles from 605 individuals (334 females and 271 males) aged 55-65 from the Taizhou Imaging Study with osteopenia (n n = 270, 170 women) or osteoporosis (n n = 94, 85 women) or normal (n = 241, 79 women) were determined using shotgun metagenomic sequencing. The linear discriminant analysis was employed to identify differentially enriched taxa. Utilizing the Kyoto Encyclopedia of Genes and Genomes for annotation, functional pathway analysis was conducted to identify differentially metabolic pathways. Polygenic risk score for osteoporosis was estimated to represent genetic susceptibility to osteoporosis, followed by stratification and interaction analyses. Gut flora diversity did not show significant differences among various bone mineral groups. After multivariable adjustment, certain species, such as Clostridium leptum, , Fusicatenibacter saccharivorans and Roseburia hominis, were enriched in osteoporosis patients. Statistically significant interactions between the polygenic risk score and taxa Roseburia faecis, Megasphaera elsdenii were observed (P P for interaction = 0.005, 0.018, respectively). Stratified analyses revealed a significantly negative association between Roseburia faecis and bone mineral density in the low-genetic-risk group (beta =-0.045, P < 0.05), while Turicimonas muris was positively associated with bone mineral density in the high-genetic-risk group (beta = 4.177, P < 0.05) after multivariable adjustments. Functional predictions of the gut microbiome indicated an increase in pathways related to structural proteins in high-genetic-risk patients, while low-genetic-risk patients exhibited enrichment in enzyme-related pathways. This study emphasizes the association between gut microbes and bone mass, offering new insights into the interaction between genetic background and gut microbiome.