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

Abstract

The Covid-19 pandemic has impacted public health dramatically in several countries. In this context, understanding the factors related to the serious forms of Covid-19 is essential for prevention and, possibly, treatment of patients. Recent studies show 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 by SARS-CoV. Briefly, we will use experimental models in which we change the intestinal microbiota and its metabolite production through the use of antibiotics, supplementation with microbiota's metabolites or diets that alter the endogenous production of these products, and we will analyze your response to SARS-CoV infection. Mice kept under different experimental conditions (diets, oral supplementation with metabolites or antibiotics) will be infected with SARS-CoV and analyzed for disease progression (weight variation and clinical signs) and subsequently euthanized for analysis of viral load, inflammatory mediators, and histological changes in the lung. In addition, we will analyze the amount of virus present in 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. (AU)