The Gut Microbiome Is Altered in Postmenopausal Women With Osteoporosis and Osteopenia. Original paper

What was studied?

This research article investigated how the gut microbiome is altered in postmenopausal women with osteoporosis and osteopenia compared to healthy controls. The study aimed to characterize microbial diversity, taxonomic composition, and functional gene potential using shotgun metagenomic sequencing of fecal samples. Researchers sought to identify specific microbial taxa and metabolic pathways associated with bone health status, focusing on elucidating microbial signatures and potential mechanisms linking gut microbiota with bone metabolism in postmenopausal women.

Who was studied?

The study cohort consisted of 86 postmenopausal women aged 54 to 81 years, all at least 5 years post-menopause, recruited from the “Bugs’n’Bones” study at Massey University, New Zealand. Exclusion criteria included any systemic disease, gut-impacting food intolerances, smoking, high alcohol intake, recent antibiotic use, or significant weight change in the prior year. None were receiving medical treatment for osteoporosis or osteopenia. Based on WHO bone mineral density (BMD) T-score criteria, participants were classified as healthy (n=26), osteopenic (n=42), or osteoporotic (n=18).

Most important findings

The study found that both osteoporotic and osteopenic women had significantly different gut microbial taxonomic compositions compared to healthy controls, although their alpha diversity (Shannon and Simpson indices) did not differ. Beta diversity analyses and PERMANOVA confirmed significant community composition differences between healthy and diseased groups. Notably, healthy women showed higher abundances of unclassified Clostridia and methanogenic archaea (Methanobacteriaceae), including Methanobrevibacter smithii, while Bacteroides was more prevalent in osteoporotic and osteopenic groups. Other taxa such as Parabacteroides distasonis, Bacteroides uniformis, and Roseburia intestinalis were more abundant in osteopenic women, while Betaproteobacteria, Bacteroides stercoris, and Adlercreutzia were elevated in osteoporosis. Functional metagenomic analysis revealed that pathways related to carbohydrate metabolism, biosynthesis of secondary metabolites, phenylpropanoid and cyanoamino acid metabolism were enriched in osteoporotic and osteopenic groups, whereas replication and repair pathways were more prominent in healthy women. These results suggest a shift in the gut microbiome from health to osteopenia and osteoporosis, with specific microbial and functional signatures.

Key implications

This study provides the first shotgun metagenomic evidence that osteoporosis and osteopenia in postmenopausal women are associated with distinct gut microbiome signatures, both taxonomically and functionally. The findings highlight increased Bacteroides and decreased Clostridia and methanogenic archaea as potential microbial markers of bone loss, with functional shifts toward increased carbohydrate metabolism and secondary metabolite biosynthesis. These alterations may influence bone metabolism through mechanisms involving immune modulation, estrogen metabolism, and short-chain fatty acid production. The results underscore the potential for developing microbiome-based biomarkers and microbiome-targeted interventions targeting gut microbial communities to support bone health in postmenopausal women.