Abstract
Background
Emerging evidence suggests that changes in the composition of the gut microbiota may not only be a consequence of AIDS but may also influence the risk of disease. However, it is not clear that these associations point to the certainty of causality.
Objective
To reveal the causal relationship between gut microbiota and AIDS, we performed a two-sample Mendelian randomization (MR) analysis.
Materials And Methods
We evaluated summary statistics of gut microbiota and HIV infection disease from published genome-wide association studies (GWAS). A two-sample MR analysis was performed to identify HIV-causing bacterial taxa in the samples based on inverse variance weighting (ivw) results. Sensitivity analyses were performed to verify the stability of the results. Finally, an inverse MR analysis was performed to assess the possibility of reverse causality.
Results
Combining the results of MR analysis and sensitivity analysis, we identified eight pathogenic bacterial genera: Subdoligaranulum (OR = 4.012,95% confidence interval [CI] = 1.783–9.027, P = 7.90E-04), Victivallis(OR = 1.605,95% CI = 1.012–2.547, P = 4.40E-02), and Ruminococcaceae_UCG-005 (OR = 2.051, 95% CI = 1.048–4.011, P = 3.60E-02) increased the risk of HIV infection. In contrast, genetically predicted Eggerthella (OR = 0.477, 95%CI = 0.283–0.805, P = 5.50E-03), Anaerotruncus (OR = 0.434, 95% CI = 0.197–0.954,P = 3.8E-02), Methanobrevibacter (OR = 0. 509 ; 95% CI = 0. 265 − 0.980; P = 4.30E-02), Clostridiumsensustricto1 (OR = 0.424, 95% CI = 0.182–0.988, P = 4.70E-02) and Coprococcus2 (OR = 0.377, 95% CI = 0.159–0.894, P = 2.70E-02) reduced the risk of HIV infection. Further sensitivity analyses verified the robustness of the above associations. Reverse MR analysis showed no evidence of reverse causality between HIV infection and the eight genera mentioned above.
Conclusion
This study demonstrates that Subdoligaranulum, Victivallis, Ruminococcaceae_UCG-005,Eggerthella, Clostridiumsensustricto1. Coprococcus2 and AIDS are causally linked, thus providing new insights into the mechanisms underlying the onset of gut microbiota-mediated HIV infection.