Influenza A virus infection impacts systemic microbiota dynamics and causes quantitative enteric dysbiosis

Abstract

BackgroundMicrobiota integrity is essential for a growing number of physiological processes. Consequently, disruption of microbiota homeostasis correlates with a variety of pathological states. Importantly, commensal microbiota provide a shield against invading bacterial pathogens, probably by direct competition. The impact of viral infections on host microbiota composition and dynamics is poorly understood. Influenza A viruses (IAV) are common respiratory pathogens causing acute infections. Here, we show dynamic changes in respiratory and intestinal microbiota over the course of a sublethal IAV infection in a mouse model.ResultsUsing a combination of 16S rRNA gene-specific next generation sequencing and qPCR as well as culturing of bacterial organ content, we found body site-specific and transient microbiota responses. In the lower respiratory tract, we observed only minor qualitative changes in microbiota composition. No quantitative impact on bacterial colonization after IAV infection was detectable, despite a robust antimicrobial host response and increased sensitivity to bacterial super infection. In contrast, in the intestine, IAV induced robust depletion of bacterial content, disruption of mucus layer integrity, and higher levels of antimicrobial peptides in Paneth cells. As a functional consequence of IAV-mediated microbiota depletion, we demonstrated that the small intestine is rendered more susceptible to bacterial pathogen invasion, in a Salmonella typhimurium super infection model.ConclusionWe show for the first time the consequences of IAV infection for lower respiratory tract and intestinal microbiobiota in a qualitative and quantitative fashion. The discrepancy of relative 16S rRNA gene next-generation sequencing (NGS) and normalized 16S rRNA gene-specific qPCR stresses the importance of combining qualitative and quantitative approaches to correctly analyze composition of organ associated microbial communities. The transiently induced dysbiosis underlines the overall stability of microbial communities to effects of acute infection. However, during a short-time window, specific ecological niches might lose their microbiota shield and remain vulnerable to bacterial invasion.Electronic supplementary materialThe online version of this article (10.1186/s40168-017-0386-z) contains supplementary material, which is available to authorized users.

Respiratory viral infection alters the gut microbiota by inducing inappetence

“…Other studies in mice have observed that respiratory virus infection is associated with a change in the gut microbiota, but none have proposed that infection-induced inappetence is the driver (Wang et al, 2014;Deriu et al, 2016;Bartley et al, 2017;Yildiz et al, 2018). Bartley et al (2017) observed that influenza infection drives the gut microbiota composition towards a profile similar to that of calorie restricted mice.…”

“…However, several studies have demonstrated that respiratory infections are associated with a change in the composition of the gut microbiota (Wang et al, 2014;Deriu et al, 2016;Bartley et al, 2017;Groves et al, 2018;Hanada et al, 2018;Yildiz et al, 2018). We have previously observed that viral lung infections alter the gut microbiota, leading to an increase in the relative abundance of Bacteroidetes and a decrease in the relative abundance of Firmicutes (Groves et al, 2018).…”

16S rRNA gene sequencing reveals an altered composition of the gut microbiota in chickens infected with a nephropathogenic infectious bronchitis virus

“…Higher diversity and integrity of gut microbiota is favourable to the intestinal ecosystem 41,42 . According to recent research, viral infection can lower microbial diversity in the gut microbiota according to recent research [43][44][45] .…”

Lung inflammation and disease: A perspective on microbial homeostasis and metabolism

“…In this context, IAV and RSV have recently been studied in detail. In a recent report, it has been shown that sublethal infection with a low-pathogenic variant of H5N1 IAV can change microbial composition in the LRT (106). The authors show a Bacillus to Lactobacillus shift in the lung microbiome, and interestingly, gut microbiome depletion and disruption of gut barrier integrity and type-1 interferon (IFN-1) response due to lung IAV infection.…”