Colonic expression of Ace2, the SARS-CoV-2 entry receptor, is suppressed by commensal human microbiota

Infection with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. Angiotensin-converting enzyme 2 (Ace2) is expressed in the gastrointestinal (GI) tract and a receptor for SARS-CoV-2, making the GI tract a potential infection site. This study investigated the effects of commensal intestinal microbiota on colonic Ace2 expression using a humanized mouse model. We found that colonic Ace2 expression decreased significantly upon microbial colonization. Humanization with healthy volunteer or dysbiotic microbiota from irritable bowel syndrome (IBS) patients resulted in similar Ace2 expression. Despite the differences in microbiota, no associations between α-diversity, β-diversity or individual taxa, and Ace2 were noted post-humanization. These results highlight that commensal microbiota play a key role in regulating intestinal Ace2 expression and the need to further examine the underlying mechanisms of this regulation.