Influenza A Virus Infection Alters Gut Microbiota Composition in Juvenile Mice

Abstract

The gut microbiota (GM) stimulates the immune system to facilitate appropriate immune responses at local and distal sites of virus infection. However, the impact of distal virus infections in modulating the composition of GM is less clear.Here, a mouse model was used to examine the effect of influenza a virus (IAV) infection on the composition of GM in mice that did or did not receive oral treatment with broad spectrum antibiotics (ABX). We focused on ABX treatment of 3 weeks old juvenile mice, as this represents a dynamic time in the establishment of GM and immunity, followed by mockor IAV-infection 2 weeks later. Mice were subsequently assessed for changes in body weight, viral load in the respiratory tract and the composition of GM. As anticipated, oral ABX treatment reduced the diversity of GM and ABX-treated mice showed exacerbated disease, characterized by enhanced weight loss and increased virus titers in the upper and lower airways. Surprisingly, IAV infection also increased the diversity of GM in ABX-treated mice, resulting in a microbial composition qualitatively and quantitatively different to mock-infected ABX-treated mice and IAV-infected mice that did not receive ABX treatment. Specifically, IAV infection increased the relative abundance of eight different bacteria in GM in ABX mice compared to the GM in mock-infected ABX mice. These findings confirm an important role for GM in functional immune defense against IAV infection in juvenile mice, consistent with previous studies in adult animals. Moreover, we report for the first time that distal IAV infection of the airways can enhance the diversity of an ABX-compromised GM.

Akkermansia muciniphila Improves Host Defense Against Influenza Virus Infection

“…In addition, interferon production in the lungs have also been reported to alter the composition of intestinal microbes (Wang et al, 2014 ; Deriu et al, 2016 ). Similar to previous studies (Fuglsang et al, 2018a , b ), we found that the abundance of A. muciniphila significantly increased after influenza infection. A recent literature has shown that influenza infection enhanced intestinal Muc2 levels (Deriu et al, 2016 ), which may be related to the upregulation of A. muciniphila , due to muc2 is an essential ingredient to maintain the growth of A. muciniphila .…”