COVID-19 (coronavirus disease 2019) patients exhibiting gastrointestinal symptoms are reported to have worse prognosis. Ace2 (angiotensin-converting enzyme 2), the gene encoding the host protein to which SARS-CoV-2 spike proteins bind, is expressed in the gut and therefore may be a target for preventing or reducing severity of COVID-19. Here we test the hypothesis that Ace2 expression in the gastrointestinal and respiratory tracts is modulated by the microbiome. We used quantitative PCR to profile Ace2 expression in germ-free mice, conventional raised specific pathogen-free mice, and gnotobiotic mice colonized with different microbiota. Intestinal Ace2 expression levels were significantly higher in germ-free mice compared to conventional mice. A similar trend was observed in the respiratory tract. Intriguingly, microbiota depletion via antibiotics partially recapitulated the germ-free phenotype, suggesting potential for microbiome-mediated regulation of Ace2 expression. Variability in intestinal Ace2 expression was observed in gnotobiotic mice colonized with different microbiota, partially attributable to differences in microbiome-encoded proteases and peptidases. Together, these data suggest that the microbiome may be one modifiable factor determining COVID-19 infection risk and disease severity.
【초록키워드】 COVID-19, coronavirus disease, Coronavirus disease 2019, disease severity, risk, Antibiotics, protease, angiotensin-converting enzyme 2, microbiota, COVID-19 infection, mice, severity of COVID-19, SARS-CoV-2 spike protein, Patient, Microbiome, phenotype, target, Proteases, respiratory tract, infection risk, respiratory, ACE2 expression, expression, quantitative PCR, Angiotensin-converting enzyme, Hypothesis, gastrointestinal symptoms, angiotensin, Spike proteins, Gut, (coronavirus disease 2019, Regulation, expression level, enzyme, These data, Variability, gastrointestinal and respiratory tracts, host protein, peptidases, SARS-CoV-2 spike proteins, worse prognosis, gene encoding, Gastrointestinal symptom, intestinal, reported, raised, reducing, expressed, significantly higher, exhibiting, specific pathogen-free, modulated, gnotobiotic, 【제목키워드】 expression, digestive,