Impact of intestinal microbiota and its metabolites on SARS-Cov-2 infection

The Covid-19 pandemic has impacted public health dramatically in several countries. In this context, understanding the factors related to the severe forms of Covid-19 is essential for the prevention and, possibly, treatment of those infected. Recent work shows that the intestinal microbiota and its products play a fundamental role in respiratory infections by other viruses including respiratory syncytial virus and Influenza virus. However, it is not known whether there is a relationship between changes in the microbiota and infection by COVID-19. In this project we will use experimental approaches already used by the group to understand the relationship between intestinal microbiota / its products and respiratory viral infection. We will soon use animal models in which we alter the intestinal microbiota and its metabolite production through the use of antibiotics, supplementation with microbiota metabolites or diets that alter the endogenous production of these products and we will analyze your response to SARS-CoV-2 infection. . Mice kept under different experimental conditions (diets, oral supplementation with metabolites or antibiotics) will be infected with SARS-CoV-2 and analyzed for disease progression (weight variation and clinical signs) and subsequently euthanized for analysis of viral load, inflammatory, cellular mediators, and histological changes in the lung. In addition, we will analyze the amount of virus present in the feces and the intestinal production of short-chain fatty acids and the composition of the intestinal microbiota. The data obtained will be complemented by analyzes performed with human cell lines and samples from infected patients.