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.