Gut microbial community and fecal metabolomic signatures in different types of osteoporosis animal models

Abstract

Background: The gut microbiota (GM) constitutes a critical factor in the maintenance of physiological homeostasis. Numerous studies have empirically demonstrated that the GM is closely associated with the onset and progression of osteoporosis (OP). Nevertheless, the characteristics of the GM and its metabolites related to different forms of OP are poorly understood. In the present study, we examined the changes in the GM and its metabolites associated with various types of OP as well as the correlations among them. Methods: We simultaneously established rat postmenopausal, disuse-induced, and glucocorticoid-induced OP models. We used micro-CT and histological analyses to observe bone microstructure, three-point bending tests to measure bone strength, and enzyme-linked immunosorbent assay (ELISA) to evaluate the biochemical markers of bone turnover in the three rat OP models and the control. We applied 16s rDNA to analyze GM abundance and employed untargeted metabolomics to identify fecal metabolites in all four treatment groups. We implemented multi-omics methods to explore the relationships among OP, the GM, and its metabolites. Results: The 16S rDNA sequencing revealed that both the abundance and alterations of the GM significantly differed among the OP groups. In the postmenopausal OP model, the bacterial genera g__Bacteroidetes_unclassified, g__Firmicutes_unclassified, and g__Eggerthella had changed. In the disuse-induced and glucocorticoid-induced OP models, g__Akkermansia and g__Rothia changed, respectively. Untargeted metabolomics disclosed that the GM-derived metabolites significantly differed among the OP types. However, a Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that it was mainly metabolites implicated in lipid and amino acid metabolism that were altered in all cases. An association analysis indicated that the histidine metabolism intermediate 4-(β-acetylaminoethyl) imidazole was common to all OP forms and was strongly correlated with all bone metabolism-related bacterial genera. Hence, 4-(β-acetylaminoethyl) imidazole might play a vital role in OP onset and progression. Conclusions: The present work revealed the alterations in the GM and its metabolites that are associated with OP. It also disclosed the changes in the GM that are characteristic of each type of OP. Future research should endeavor to determine the causal and regulatory effects of the GM and the metabolites typical of each form of OP.

Interpretable machine learning reveals microbiome signatures strongly associated with dairy cow milk urea nitrogen

“…In the investigation of osteoporosis, a significant difference in g__Firmicutes_unclassified was observed by the mouse model. 22 The g__Dorea was significantly associated with diarrhea and health in calves. 23 The g_Lactobacillus can enhance cattle immunity and improve feed conversion efficiency.…”

Gut microbiota, plasma metabolites, and osteoporosis: unraveling links via Mendelian randomization

“…This analytical approach has enabled researchers to identify specific metabolites that are predictive of various aspects related to OP ( Lau et al, 2023 ). These include forecasting the onset of the disease ( Miyamoto et al, 2021 ), identifying low BMD in postmenopausal women ( Miyamoto et al, 2018 ), distinguishing between osteopenia and OP ( Aleidi et al, 2021 ), enhancing the accuracy of fracture risk predictions ( Zhang et al, 2021 ), and revealing the specific changes in the GM characteristic of each type of OP ( Qiao et al, 2024 ). While numerous MR studies have been conducted to investigate the relationship between blood metabolites and BMD ( Moayyeri et al, 2017 ; Liu et al, 2018 ; Zhang et al, 2021 ; Chen and He, 2023 ), there remains a limited number of studies specifically targeting the phenotype of OP.…”