Functional Characterization Of Covid-19 Patient Gut Microbiome (FunBiome)

While COVID-19 is mainly considered an airway and lung disease, up to 79% of patients present with gastrointestinal symptoms and recent studies report on the presence of SARS-CoV-2 viral RNA and particles in stools of infected patients, suggesting that the gastrointestinal (GI) tract may have a more important involvement in disease pathology than previously thought. The GI tract is also the site of the dense and diverse microbiome, which has the ability to regulate intestinal and systemic immunity through the conversion of dietary nutrients into bioactive metabolites. Consequently, perturbations in the microbiome composition may drive susceptibility to or participate in worsening disease pathology. This project aims at functionally characterizing the COVID-19 patient gut microbiome at the genomic and metabolic level in order to highlight a disease susceptibility signature and consequences for immunity to SARS-CoV-2. To this aim, we propose to collect stools and blood from COVID-19 positive individuals in the framework of existing CON-VINCE and PREDI-COVID cohort studies. Through metagenomic and metatranscriptomic sequencing of the DNA and RNA extracted from stool samples, we will characterize the strain-level taxonomic composition and functional capacity with respect to the carbohydrate-active enzyme (CAZyme) repertoire of the gut microbiome. Due to their documented role in immunomodulation, especially in the context of viral infection, we will also quantify levels of short-chain fatty acids in stools and sera. We will investigate the association of these metabolic markers to key antiviral immune pathways in the peripheral blood. The results will be paralleled with dietary habits and medical information to define disease susceptibility profiles in the healthy population, as well as outcome prediction models in diagnosed patients.