Association between gut microbiota and influenza: a bidirectional two-sample mendelian randomization study

Abstract

Background Previous observational studies have indicated a correlation between the gut microbiota and influenza; however, the exact nature of the bidirectional causal connection remains uncertain. Method A two-way, two-sample Mendelian randomization (MR) study was conducted to evaluate the possible causal connection between the gut microbiota and the two outcomes of influenza (pneumonia without influenza and influenza pneumonia). The statistical analysis of gut microbiota is derived from the information of the most extensive meta-analysis (GWAS) conducted by the MiBioGen Alliance, encompassing a sample size of 18,340.The summary statistical data for influenza (not pneumonia, n = 291,090) and influenza pneumonia (n = 342,499) are from GWAS data published by FinnGen consortium R8.Estimate and summarize Single-nucleotide polymorphisms (SNPs) using Inverse variance weighted (IVW), MR Egger, and Weighted median (WM) in bidirectional MR analysis. To assess the heterogeneity, horizontal pleiotropy, and stability of SNPs, we employed Cochran’s Q test, MR Egger intercept test, and sensitivity analysis. Result The IVW analysis indicated that there was a significant association between influenza infection and five bacterial taxa. Additionally, the abundance changes of seven gut microbiota were found to be causally related to influenza infection. In addition, seven bacterial taxa showed a significant association with the occurrence of influenza pneumonia. The findings from the WM analysis largely support the outcomes of IVW, however, the results of MR egger analysis do not align with IVW. Furthermore, there is no proof to substantiate the cause-and-effect relationship between influenza pneumonia and the composition of gut microbiota. Conclusion This analysis demonstrates a possible bidirectional causal connection between the prevalence of particular gut microbiota and the occurrence of influenza infection. The presence of certain gut microbiota may potentially contribute to the development of pneumonia caused by influenza. Additional investigation into the interaction between particular bacterial communities and influenza can enhance efforts in preventing, monitoring, and treating influenza.

Identification of Causal Relationships between Gut Microbiota and Influenza a Virus Infection in Chinese by Mendelian Randomization

“…The bacterial strains present in the bacterial formulation enhanced the production of both nuclear factor erythroid 2p45-related factor 2 and its target Heme oxygenase-1, exerting antiviral effects through the reduction of oxidative stress [ 72 ]. Interestingly, Xu et al reported that the genus Streptococcus was negatively associated with influenza outcomes in FinnGen cohorts, consistent with our findings in the Chinese population [ 22 ]. However, we also found that Streptococcus mitis was positively associated with H7N9 susceptibility.…”

“…Xu et al employed MR to investigate the causal effect of gut microbiota on seasonal influenza and influenza-induced pneumonia in Finland. In their study, the identification of intestinal flora was limited to the genus level [ 22 ]. In this study, we performed a systematic two-sample MR study to explore the causal effect of species-level gut microbiota on avian IAV H7N9 susceptibility and H1N1pdm09 severity in Chinese.…”