Gut microbiota and metabolite alterations associated with reduced bone mineral density or bone metabolic indexes in postmenopausal osteoporosis

Abstract

Reduced bone mineral density (BMD) is associated with an altered microbiota in senile osteoporosis. However, the relationship among gut microbiota, BMD and bone metabolic indexes remains unknown in postmenopausal osteoporosis. In this study, fecal microbiota profiles for 106 postmenopausal individuals with osteopenia (n=33) or osteoporosis (n=42) or with normal BMD (n=31) were determined. An integrated 16S rRNA gene sequencing and LC-MS-based metabolomics approach was applied to explore the association of estrogen-reduced osteoporosis with the gut microbiota and fecal metabolic phenotype. Adjustments were made using several statistical models for potential confounding variables identified from the literature. The results demonstrated decreased bacterial richness and diversity in postmenopausal osteoporosis. Additionally, showed significant differences in abundance levels among phyla and genera in the gut microbial community were found. Moreover, postmenopausal osteopenia-enriched N-acetylmannosamine correlated negatively with BMD, and distinguishing metabolites were closely associated with gut bacterial variation. Both serum procollagen type I N propeptide (P1NP) and C-terminal telopeptide of type I collagen (CTX-1) correlated positively with osteopenia-enriched Allisonella, Klebsiella and Megasphaera. However, we did not find a significant correlation between bacterial diversity and estrogen. These observations will lead to a better understanding of the relationship between bone homeostasis and the microbiota in postmenopausal osteoporosis.

A Multi-Omic Analysis for Low Bone Mineral Density in Postmenopausal Women Suggests a Relationship between Diet, Metabolites, and Microbiota

“…Our results are consistent with other studies suggesting that low-BMD subjects have fewer observed species than the normal-BMD group [ 28 , 29 ]. The mechanisms underlying the decrease in observed species in low-BMD women remain elusive.…”

“…In the present study, the abundance of Klebsiella and Erwinia genus belonging to γ- Proteobacteria phylum were increased in the group with low-BMD compared with the normal group. This finding coincides with that recently reported by He et al in postmenopausal women with osteopenia [ 29 ]. Interestingly, during intestinal dysbiosis, it has been observed that mice have less femur bending strength, deterioration in the properties of bone tissue, and a greater abundance of Proteobacteria [ 31 ].…”

The Association between Gut Microbiota and Osteoporosis was Mediated by Amino Acid Metabolism: Multi-omics Integration in a Large Adult Cohort

“…To date, only limited cross-sectional studies had reported the association between gut microbiota and bone density or osteoporosis and showed inconsistent results [14,15,16,17]. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint…”

“…To date, only limited cross-sectional studies had reported the association between gut microbiota and bone density or osteoporosis and showed inconsistent results [14, 15, 16, 17]. Higher proportions of Blautia and Parabacteroides , but lower proportion of Ruminococcaceae UCG-002 , were observed in 12 osteopenia/osteoporotic subjects than in 6 normal controls in Xi’an China [14], while Actinomycetes, Eggerthella, Clostridium X1Va and Lactobacilli were more abundant in 61 osteoporotic patients than in the 60 normal group in Irish [15].…”

“…The gut microbiota or it metabolites can also induce bone remodeling, which may be mediated by elevated serum IGF-1 levels in mice [18]. Few studies explored the associations between microbial function [16, 19] or fecal metabolites [17] and bone health in human adults. It was found that low-BMD/osteopenia might be related to a wide range of potential pathways (e.g., LPS biosynthesis, Membrane transport) [16, 19], or fecal metabolites like N-acetylmannosamine, deoxyadenosine, and adenosine [17].…”