Causal relationship between gut microbiota and viral infectious disease: A 2-sample Mendelian randomization study

The interaction of the dysbiosis of the gut microbiota (GM) with viral infectious disease (VID) has drawn our attention, and a better understanding of the effects of GM on VID might provide potential therapeutic approaches. However, the causal effects between GM and different types of VID remain unclear. We aimed to reveal the causal relationships between GM and VID, including adenovirus, cytomegalovirus, Epstein-Barr virus (EBV), influenza virus subtype H1N1 (H1N1) and herpes simplex virus 1 (HSV-1) infection. The GM and 5 VID types, namely, adenovirus, cytomegalovirus, EBV, H1N1 and HSV-1, were identified from large-scale genome-wide association study summary data. We used Mendelian randomization (MR) to investigate the causal relationships between GM and the 5 types of VID. MR-Egger, weighted median, inverse variance weighted, simple mode and weighted mode were used to examine the causal associations between GM and VID. Inverse variance weighting was used as the main statistical method. Sensitivity analysis was performed via the MR-Egger regression intercept method and Cochran's Q test. There were 9 positive and 14 negative causal effects between genetic liability in the GM and 5 types of VID. Specifically, the results revealed 6 associated genera in the adenovirus group, 5 associated genera in the cytomegalovirus group, 4 associated genera in the EBV group, 3 associated genera in the H1N1 group and 5 associated genera in the HSV-1 group. The causal relationship between the GM and VIDs provides new ideas and a pretheoretical basis for exploring microbiota transplantation as a strategy for treating VID.