Early-Life SARS-CoV-2 Infection Disrupts Gut Microbiota and Metabolic Programming in a Neonatal Non Human Primate Model

Microbiota is a critical regulator of the immune system development and homeostasis, and its composition and function can be modulated by various factors, including respiratory viral infections, e.g SARS-CoV-2. Using a neonate non-human primate preclinical model, we characterized the microbiota composition and metabolite profiles under both physiological and infectious conditions. We show that although SARS-CoV-2 infection was clinically mild, it significantly disrupted the normal trajectory of gut microbiota colonization and metabolic programming in neonates. This disruption is characterized by a depletion of Bifidobacterium species and altered activity in key metabolic pathways, including tryptophan and polyamine metabolism through variations in kynurenine or ornithine levels, which are crucial for immune development and gut homeostasis, respectively. These results indicate that even mild viral infections in early-life can disrupt microbiota homeostasis, potentially leading to long-term alterations in immune development through microbiota-derived metabolites.