SARS-CoV-2 infection induced gut dysbiosis in a novel hACE2 mouse model

The cutting-edge evidence indicates that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection associates with gut dysbiosis in patients with coronavirus disease 2019 (COVID-19), and thus may contribute to severe disease. Mechanistic links underlying the pathogenic effects of gut dysbiosis are needed to be elucidated. However, the animal models commonly used in current studies are not identified to show the intestinal susceptibility to SARS-CoV-2. In this study, we used a novel humanized ACE2 (hACE2) knock-in mouse model which can recapitulate some hallmark features of pulmonary and intestinal infection to investigate the alterations of gut microbiome post SARS-CoV-2 infection. Fecal 16S rRNA gene profiling indicates significant reduction of species richness and obvious changes of microbiome composition at 6 days post infection (dpi). These changes in the relative bacterial abundance are generally characterized by depletion of beneficial bacteria and enrichment of certain opportunistic pathogens. Further correlation analysis between gut microbiome and concentrations of plasma cytokines is performed, revealing that the genera of Lachnospiraceae_NK4A136_group and unclassified_f_Lachnospiraceae may play an important role in reducing hyperinflammatory responses to infection. Moreover, the results of gut microbiome and RNA-seq analysis indicate that increase abundance of Staphylococcus in feces points toward the possibility of bacterial coinfection in lung tissues occurred through gut translocation. Collectively, our mouse model is able to recur the changes of gut microbiome during course of SARS-CoV-2 infection, providing a useful tool to investigate the gut microbiome-targeted approaches for the control of COVID-19.