Altered Gut Microbiota and Predicted Immune Dysregulation in Early Childhood SARS-CoV-2 Infection

The gut microbiome plays a key role in immune regulation. Young children experience rapid microbiome development, yet data on its alteration during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remain limited. This study aimed to characterize gut microbiome changes and immune-related pathway alterations in young children with coronavirus disease 2019 (COVID-19). Eighteen children under 2 years old with confirmed SARS-CoV-2 infection and seven healthy controls were enrolled between December 2021 and June 2022. Stool samples were analyzed using 16S rRNA gene sequencing. In children with COVID-19, the gut microbiome exhibited an increase in Bacteroidota and Bacillota, whereas Actinomycetota and Pseudomonadota were reduced, with higher abundances of Bifidobacterium, Escherichia, and Streptococcus and lower abundances of Faecalibacterium, Clostridium, and Ruminococcus compared with healthy controls. Children with COVID-19 exhibited reduced alpha diversity, indicating microbial dysbiosis, and significant differences in beta diversity compared with healthy controls. Predictive functional analysis revealed downregulation of key immune-related pathways, such as interleukin-17, NOD-like receptor, and Toll-like signaling, which may impact mucosal immunity and viral clearance in children with COVID-19. SARS-CoV-2 infection in early childhood is associated with gut dysbiosis and the suppression of key immune pathways. These findings highlight the potential long-term impact of early-life microbial disruptions on immune development.