Decreased Microbiota-Driven Tyrosine Metabolism Is Associated With Symptomatic COVID-19 in Children.

Abstract

The gut microbiota has been implicated in driving coronavirus disease 2019 (COVID-19) disease severity, but the underlying mechanisms remain unknown. We investigated the relationship between the gut microbiota and development of symptomatic COVID-19 in children. We prospectively collected stool and plasma samples from 229 children who were exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including 45 COVID-19 negative, 57 with asymptomatic COVID-19, and 127 with symptomatic COVID-19. We performed shotgun metagenomic sequencing on the stool samples to characterize the microbial taxa and functional profiles. Plasma cytokine levels were measured in SARS-CoV-2-infected individuals. Children with symptomatic COVID-19 had reduced microbial biodiversity and decreased functional capacity for several metabolic pathways, including a reduction in the tyrosine biosynthesis pathway, as compared to SARS-CoV-2-uninfected children or those with asymptomatic infection. The abundance of the tyrosine biosynthesis pathway was associated with plasma levels of interferon alpha (IFN-α), which were lower in children with symptomatic COVID-19. Our findings highlight a relationship between the ability of the gut microbiota to metabolize tyrosine and the development of COVID-19 symptoms in children. More generally, our study suggests that the gut microbiota may help protect against more severe forms of COVID-19, potentially by modulating IFN-α.