Molecular Characterization of Influenza Virus in Intestines and its Effect on Intestinal Microbiota

Abstract

Background: Influenza predominantly causes respiratory diseases; however, gastrointestinal symptoms are not uncommonly reported, particularly among high-risk groups. Influenza virus RNA has been also detected in stools of patients infected with pandemic and seasonal influenza, however, the role and the clinical significance of intestinal infection has not been clearly demonstrated. Methods: Here, we used NGS technology to investigate molecular characterization of viral RNA shedding in feces of adults with active influenza infection. Paired nasal and fecal samples were collected from 295 patients showing to emergency department at Hamad Medical Corporation with flu-like symptoms during January 2018 and April 2019. Results: Among these, 90 nasal samples were positive for influenza, of which, 26 fecal samples were positive for influenza in real-time PCR and only five showed virus growth in both monolayer and 3D cell culture. Full genome sequencing of isolated viruses revealed some unique mutations that we are currently in the process of studying their effect on virus kinetics. Then, we investigated the potential impact of respiratory influenza infection on intestinal microbiota diversity and composition. Microbiome analysis results suggest that changes in gut microbiota composition in influenza-infected patients are significantly associated with (1) influenza virus type, and (2) the presence of viral RNA in intestines of infected patients. We also identified bacterial taxa for which relative abundance was significantly higher in the patients with severe respiratory symptoms. Conclusion: Altogether, our findings suggest that influenza viruses can affect intestinal environment either by direct intestinal infection or indirectly by modulating intestinal microbiota.