Abstract
Numerous studies have reported a correlation between gut microbiota and influenza A virus (IAV) infection and disease severity. However, the causal relationship between these factors remains inadequately explored. This investigation aimed to assess the influence of gut microbiota on susceptibility to human infection with H7N9 avian IAV and the severity of influenza A (H1N1)pdm09 infection. A two-sample Mendelian randomization analysis was conducted, integrating our in-house genome-wide association study (GWAS) on H7N9 susceptibility and H1N1pdm09 severity with a metagenomics GWAS dataset from a Chinese population. Twelve and fifteen gut microbiotas were causally associated with H7N9 susceptibility or H1N1pdm09 severity, separately. Notably, Clostridium hylemonae and Faecalibacterium prausnitzii were negative associated with H7N9 susceptibility and H1N1pdm09 severity, respectively. Moreover, Streptococcus peroris and Streptococcus sanguinis were associated with H7N9 susceptibility, while Streptococcus parasanguini and Streptococcus suis were correlated with H1N1pdm09 severity. These results provide novel insights into the interplay between gut microbiota and IAV pathogenesis as well as new clues for mechanism research regarding therapeutic interventions or IAV infections. Future studies should concentrate on clarifying the regulatory mechanisms of gut microbiota and developing efficacious approaches to reduce the incidence of IAV infections, which could improve strategy for preventing and treating IAV infection worldwide.