Gut microbiota-mediated protection against influenza virus subtype H9N2 in chickens is associated with modulation of the innate responses

Abstract

Commensal gut microbiota plays an important role in health and disease. The current study was designed to assess the role of gut microbiota of chickens in the initiation of antiviral responses against avian influenza virus. Day-old layer chickens received a cocktail of antibiotics for 12 (ABX-D12) or 16 (ABX-D16) days to deplete their gut microbiota, followed by treatment of chickens from ABX-12 with five Lactobacillus species combination (PROB), fecal microbial transplant suspension (FMT) or sham treatment daily for four days. At day 17 of age, chickens were challenged with H9N2 virus. Cloacal virus shedding, and interferon (IFN)-α, IFN-β and interleukin (IL)-22 expression in the trachea, lung, ileum and cecal tonsils was assessed. Higher virus shedding, and compromised type I IFNs and IL-22 expression was observed in ABX-D16 chickens compared to control, while PROB and FMT showed reduced virus shedding and restored IL-22 expression to levels comparable with undepleted chickens. In conclusion, commensal gut microbiota of chickens can modulate innate responses to influenza virus subtype H9N2 infection in chickens, and modulating the composition of the microbiome using probiotics- and/or FMT-based interventions might serve to promote a healthy community that confers protection against influenza virus infection in chickens.

The Intestinal Microbiota Contributes to the Control of Highly Pathogenic H5N9 Influenza Virus Replication in Ducks

“…Here we provide evidence that ABX-mediated depletion of the intestinal microbiota caused an increase in H5N9 HPAIV replication in the digestive tract of ducks and was associated with a reduction of the antiviral immune response in the intestine. Similar results were observed in the digestive tract of chickens infected with a LPAIV (18, 19). Depletion of the gut microbiota in mice and chicken was associated with an increase in influenza virus replication in the respiratory tract (13, 14, 18, 19).…”

“…Similar results were observed in the digestive tract of chickens infected with a LPAIV (18, 19). Depletion of the gut microbiota in mice and chicken was associated with an increase in influenza virus replication in the respiratory tract (13, 14, 18, 19). By contrast, we did not detect a significant increase in influenza virus replication in the respiratory tract of ducks suggesting that this difference could be due to the viral strain used or host factors.…”

“…The gut microbiota is now recognized as a regulator of many physiological functions in the host, reaching far beyond its contribution to digestion (12). Several studies have highlighted the role of the gut microbiota in shaping the antiviral immune response against influenza virus, in mammals, in which the virus replicates in the respiratory tract (13–17), as well as following LPAIV infection in chickens, in which the virus replicates in the respiratory and digestive tract (18, 19).…”

Fecal microbiota in horses with asthma

“…In asthmatic horses, change in diet and environment affects the relative composition of low‐abundance taxa, which could explain changes in alpha diversity indices that are more affected by rare taxa (Shannon index but not Simpson index increased in asthmatic horses, Jaccard membership but not Yue and Clayton structure, LEfSe analysis but not in the relative abundances of the most common phyla or genera). Although our study is merely descriptive, it could be speculated that systemic inflammation induced by the upregulated immune system of asthmatic horses might influence the intestinal environment . In return, altered intestinal microbiota could affect systemic and pulmonary inflammation by changes in the absorption of short‐chain fatty acids or bacterial (ie “bacterial wall”)‐wall components (eg, endotoxin) and local or distant cytokine upregulation …”

“…Although our study is merely descriptive, it could be speculated that systemic inflammation induced by the upregulated immune system of asthmatic horses might influence the intestinal environment. 16 In return, altered intestinal microbiota could affect systemic and pulmonary inflammation by changes in the absorption of short-chain fatty acids or bacterial (ie "bacterial wall")-wall components (eg, endotoxin) and local or distant cytokine upregulation. 4,17…”