TY - JOUR

T1 - Influenza A Virus Infection Alters Gut Microbiota Composition in Juvenile Mice

AU - Fuglsang, Eva

AU - Krych, Lukasz

AU - Nielsen, Dennis Sandris

AU - Frøkiær, Hanne

AU - Reading, Patrick C.

PY - 2018

Y1 - 2018

N2 - The gut microbiota (GM) stimulates the immune system to facilitate appropriate immune responses at local and distalsites 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 micethat did or did not receive oral treatment with broad spectrum antibiotics (ABX). We focused on ABX treatment of 3weeks 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 respiratorytract and the composition of GM. As anticipated, oral ABX treatment reduced the diversity of GM and ABX-treated miceshowed exacerbated disease, characterized by enhanced weight loss and increased virus titers in the upper and lowerairways. Surprisingly, IAV infection also increased the diversity of GM in ABX-treated mice, resulting in a microbialcomposition qualitatively and quantitatively different to mock-infected ABX-treated mice and IAV-infected mice that didnot receive ABX treatment. Specifically, IAV infection increased the relative abundance of eight different bacteria in GM inABX mice compared to the GM in mock-infected ABX mice. These findings confirm an important role for GM in functionalimmune defense against IAV infection in juvenile mice, consistent with previous studies in adult animals. Moreover, wereport for the first time that distal IAV infection of the airways can enhance the diversity of an ABX-compromised GM.

AB - The gut microbiota (GM) stimulates the immune system to facilitate appropriate immune responses at local and distalsites 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 micethat did or did not receive oral treatment with broad spectrum antibiotics (ABX). We focused on ABX treatment of 3weeks 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 respiratorytract and the composition of GM. As anticipated, oral ABX treatment reduced the diversity of GM and ABX-treated miceshowed exacerbated disease, characterized by enhanced weight loss and increased virus titers in the upper and lowerairways. Surprisingly, IAV infection also increased the diversity of GM in ABX-treated mice, resulting in a microbialcomposition qualitatively and quantitatively different to mock-infected ABX-treated mice and IAV-infected mice that didnot receive ABX treatment. Specifically, IAV infection increased the relative abundance of eight different bacteria in GM inABX mice compared to the GM in mock-infected ABX mice. These findings confirm an important role for GM in functionalimmune defense against IAV infection in juvenile mice, consistent with previous studies in adult animals. Moreover, wereport for the first time that distal IAV infection of the airways can enhance the diversity of an ABX-compromised GM.

M3 - Journal article

VL - 2

JO - Journal of Infectious Diseases & Travel Medicine

JF - Journal of Infectious Diseases & Travel Medicine

SN - 2640-2653

IS - 3

M1 - 000118

ER -