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 <i>Bifidobacterium</i>, <i>Escherichia</i>, and <i>Streptococcus</i> and lower abundances of <i>Faecalibacterium</i>, <i>Clostridium</i>, and <i>Ruminococcus</i> 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.