Gnotobiotic Rats Reveal That Gut Microbiota Regulates Colonic mRNA of <i>Ace2</i> , the Receptor for SARS-CoV-2 Infectivity
Tao Yang, Saroj Chakraborty, Piu Saha, Blair Mell, Xi Cheng, Ji‐Youn Yeo, Xue Mei, Guannan Zhou, Juthika Mandal, Rachel M. Golonka, Beng San Yeoh, Vasanta Putluri, Danthasinghe Waduge Badrajee Piyarathna, Nagireddy Putluri, Cameron G. McCarthy, Camilla F. Wenceslau, Arun Sreekumar, Andrew T. Gewirtz, Matam Vijay–Kumar, Bina Joe
Abstract
e1T he coronavirus disease 2019 (COVID-19) pandemic, caused by the novel coronavirus named severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has led to an unprecedented medical crisis.Current lack of data from experimental animals makes it difficult to understand the pathophysiological mechanisms of COVID-19.A clinical study from COVID-19-positive patients in Hubei, China revealed that 46% presented with gastrointestinal problems. 1Also, SAR-CoV-2 viral RNA has been detected in the stools of patients with COVID-19.These data suggest the underestimated importance of intestinal infection in SARS-CoV-2-induced severe respiratory response. 2ACE2 (angiotensin-converting enzyme 2), the receptor for SARS-CoV-2, 3 is best known for its role in blood pressure regulation.Additionally, ACE2 has another important function of curbing intestinal inflammation.Ace2 -/-mice with a reshaped gut microbiota were susceptible to intestinal inflammation. 4ransfer of the Ace2 -/-gut microbiota to germ-free (GF) mice worsened colitis pathogenesis, 4 suggesting gut microbiotamediated protective effects of ACE2.These gastrointestinal benefits of ACE2 may be masked during coronavirus infection, where its expression in the intestine represents a possible avenue for viral entry.We speculated that gut microbiota, which is highly variable between individuals could be an additional factor modulating colonic Ace2 expression and thereby influencing COVID-19 infectivity. Methods AnimalsSeven-week-old male GF Sprague Dawley (SD) rats (N=5) and GF rats co-housed with conventional SD rats for 10 days (conventionalized GF [GFC]; N=6) were obtained from Taconic Biosciences (https://www.taconic.com/).They were immediately sacrificed with excess of isoflurane anesthesia upon arrival at the University of Toledo.Fecal samples were collected from the colon for analysis.