Murine intestinal and respiratory microbiome during monocausal pneumococcal and influenza infection

With annually 2.56 million deaths worldwide, pneumonia is one of the leading causes of death. The most frequent causative pathogens are Streptococcus pneumoniae (S. pneumoniae) and influenza A virus. Lately, the interaction between pathogens, the host and its microbiome gained more attention. The microbiome is known to promote immune response towards pathogens, however, our knowledge on how infections affect the microbiome is still scarce. Here, the impact of colonization and infection with S. pneumoniae and influenza A virus, on structure and function of the respiratory and gastrointestinal microbiomes of mice was investigated. Using a meta-omics approach we identified specific differences between the bacterial and viral infection. Pneumococcal colonization had minor effects on the taxonomic composition of the respiratory microbiome, while acute infections caused decreased microbial complexity. In contrast, richness was unaffected following H1N1 infection. Within the gastrointestinal microbiome, we found exclusive changes in structure and function depending on the pathogen. While pneumococcal colonization had no effects on taxonomic composition of the gastrointestinal microbiome, increased abundance of Akkermansiaceae and Spirochaetaceae as well as decreased amounts of Clostridiaceae were exclusively found during invasive S. pneumoniae infection. Presence of Staphylococcaceae was specific for viral pneumonia. Investigation of the intestinal microbiome ´s functional composition revealed reduced expression of flagellin and rubrerythrin and increased levels of ATPase during pneumococcal infection, while increased amounts of acetyl-CoA acetyltransferase and, enoyl-CoA transferase were unique after H1N1 infection. In conclusion, identification of specific taxonomic and functional profiles of the respiratory and gastrointestinal microbiome allowed the discrimination between bacterial and viral pneumonia.