Gut microbiota and plasma metabolites associated with bone mineral density in women with or at risk of HIV infection.

OBJECTIVE: To evaluate gut microbiota (GMB) alterations and metabolite profile perturbations associated with bone mineral density (BMD) in the context of HIV infection. DESIGN: Cross-sectional studies of 58 women with chronic HIV infection receiving antiretroviral therapy and 33 women without HIV infection. METHODS: We examined associations of GMB and metabolites with BMD among 91 women. BMD was measured by dual-energy X-ray absorptiometry (DXA), and T -scores of lumbar spine or total hip less than -1 defined low BMD. GMB was measured by 16S rRNA V4 region sequencing on fecal samples, and plasma metabolites were measured by liquid chromatography-tandem mass spectrometry. Associations of GMB with plasma metabolites were assessed in a larger sample (418 women; 280 HIV+ and 138 HIV-). RESULTS: Relative abundances of five predominant bacterial genera ( Dorea , Megasphaera , unclassified Lachnospiraceae, Ruminococcus , and Mitsuokella ) were higher in women with low BMD compared with those with normal BMD (all linear discriminant analysis (LDA) scores >2.0). A distinct plasma metabolite profile was identified in women with low BMD, featuring lower levels of several metabolites belonging to amino acids, carnitines, caffeine, fatty acids, pyridines, and retinoids, compared with those with normal BMD. BMD-associated bacterial genera, especially Megasphaera , were inversely associated with several BMD-related metabolites (e.g. 4-pyridoxic acid, C4 carnitine, creatinine, and dimethylglycine). The inverse association of Megasphaera with dimethylglycine was more pronounced in women with HIV infection compared with those without HIV infection ( P for interaction = 0.016). CONCLUSION: Among women with and at risk of HIV infection, we identified altered GMB and plasma metabolite profiles associated with low BMD.