Abstract
BackgroundInfluenza is a severe respiratory illness that continually threatens global health. It has been widely known that gut microbiota modulates the host response to protect against influenza infection, but mechanistic details remain largely unknown. Here, we took advantage of the phenomenon of lethal dose 50 (LD50) and metagenomic sequencing analysis to identify specific anti-influenza gut microbes and analyze the underlying mechanism.ResultsTransferring fecal microbes from mice that survive virulent influenza H7N9 infection into antibiotic-treated mice confers resistance to infection. Some gut microbes exhibit differential features to lethal influenza infection depending on the infection outcome. Bifidobacterium pseudolongum and Bifidobacterium animalis levels are significantly elevated in surviving mice when compared to dead or mock-infected mice. Oral administration of B. animalis alone or the combination of both significantly reduces the severity of H7N9 infection in both antibiotic-treated and germ-free mice. Functional metagenomic analysis suggests that B. animalis mediates the anti-influenza effect via several specific metabolic molecules. In vivo tests confirm valine and coenzyme A produce an anti-influenza effect.ConclusionsThese findings show that the severity of influenza infection is closely related to the heterogeneous responses of the gut microbiota. We demonstrate the anti-influenza effect of B. animalis, and also find that the gut population of endogenous B. animalis can expand to enhance host influenza resistance when lethal influenza infection occurs, representing a novel interaction between host and gut microbiota. Further, our data suggest the potential utility of Bifidobacterium in the prevention and as a prognostic predictor of influenza.
Highlights
Influenza is a severe respiratory illness that continually threatens global health
Clinical signs and pulmonary histopathological lesions are different in mice that succumbed to or survived the influenza infection To assess the heterogeneity in the host response to influenza, we infected specific pathogen-free (SPF) C57BL/6 mice with virulent (GX) and attenuated (HB) H7N9 virus using the lethal dose 50 (LD50) approach
At day 10 post-infection, the mice in the GX group that died formed the GX.DG group, whereas those mice that survived and started to show signs of improvement comprised the GX.SG group. Both autopsy and histological examination revealed that the lung lesions in the GX.DG mice were notably more severe than those in the GX.SG mice (Fig. 1c and Additional file 1: Fig S1). These findings demonstrated that mice that succumbed to or survived infection with the same dose of influenza virus have clearly different clinical signs and obvious histopathological differences, representing a heterogeneous response to infection and confirming that the LD50 approach can be used to differentiate between individual-specific responses to infection
Summary
Influenza is a severe respiratory illness that continually threatens global health. It has been widely known that gut microbiota modulates the host response to protect against influenza infection, but mechanistic details remain largely unknown. Influenza is an acute communicable respiratory illness that affects the upper and lower respiratory passages and severely threatens human health [6]. Commensal microbiota regulates the immune response against influenza by activating the inflammasome via Toll-like receptors [9]. Microbial metabolites, such as desaminotyrosine, exert a protective effect against influenza via interferon I signaling [10]. Despite all of this, the mechanistic details about the anti-influenza effects of gut microbiota remain largely unknown
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call