Growing evidence suggests that the gut microbiota and their metabolites are associated with bone homeostasis and fragility. However, this association is limited to microbial taxonomic differences. This study aimed to explore whether gut bacterial community associations, composition, and functions are associated with osteopenia and osteoporosis. We compared the gut bacterial community composition and interactions of healthy postmenopausal women with normal bone density (n = 8) with those of postmenopausal women with osteopenia (n = 18) and osteoporosis (n = 21) through 16S rRNA sequencing coupled with network biology and statistical analyses. The results of this study showed reduced alpha diversity in patients with osteoporosis, followed by that in patients with osteopenia, then in healthy controls. Taxonomic analysis revealed that significantly enriched bacterial genera with higher abundance was observed in patients with osteoporosis and osteopenia than in healthy subjects. Additionally, a co-occurrence network revealed that, compared to healthy controls, bacterial interactions were higher in patients with osteoporosis, followed by those with osteopenia. Further, NetShift analysis showed that a higher number of bacteria drove changes in the microbial community structure of patients with osteoporosis than osteopenia. Correlation analysis revealed that most of these driver bacteria had a significant positive relationship with several significant metabolic pathways. Further, ordination analysis revealed that height and T-score were the primary variables influencing the gut microbial community structure. Taken together, this study evaluated that microbial community interaction is more important than the taxonomic differences in knowing the critical role of gut microbiota in postmenopausal women associated with osteopenia and osteoporosis. Additionally, the significantly enriched bacteria and functional pathways might be potential biomarkers for the prognosis and treatment of postmenopausal women with osteopenia and osteoporosis.
Keywords: 16S rRNA sequencing; driver bacteria; functional prediction; gut microbiota; osteopenia; osteoporosis.