Altered gut microbial functional landscape in children with pediatric inflammatory multisystem syndrome following SARS-CoV-2 infection: an exploratory metagenomic study
Background: Pediatric Inflammatory Multisystem Syndrome (PIMS), also known as MIS-C, is a severe post-infectious inflammatory condition associated with SARS-CoV-2 in children. While COVID-19 primarily affects the respiratory system, growing evidence highlights gastrointestinal involvement and the relevance of the gut-lung axis in systemic inflammation. However, the contribution of the gut microbiota to PIMS pathophysiology remains insufficiently explored.Methods: This exploratory study analyzed fecal samples from 12 pediatric patients diagnosed with PIMS and 11 age-matched clinically healthy controls using shotgun metagenomic sequencing. Taxonomic profiling was performed with MetaPhlAn4, and functional and metabolic pathway analyses were conducted using HUMAnN3. Alpha and beta diversity metrics were assessed, and differential abundance analyses were applied to identify microbial taxa and putative functional pathways associated with PIMS.Results: Alpha diversity indices did not differ significantly between groups, although consistently lower mean values were observed in PIMS patients. In contrast, beta diversity analysis demonstrated a significant separation in microbial community composition between PIMS patients and controls (PERMANOVA, p = 0.01). PIMS patients exhibited increased relative abundance of Prevotella copri clade C, Duodenibacillus massiliensis, Phascolarctobacterium succinatutens, and Enterocloster bolteae, alongside a relative reduction of several commensal taxa. Putative functional profiling revealed significant differences in metabolic pathways and enzyme-coding genes related to inflammatory and immunomodulatory processes, including an increased abundance of aconitate hydratase in the PIMS group.Conclusion: These findings suggest that PIMS could be partially modulated by gut microbiota unbalance and microbial functional alterations, supporting a potential role of the gut microbiome in post-COVID-19 systemic inflammation in pediatric population. This study provides a basis for further and longitudinal investigations aimed at identifying microbial-based biomarker targets in PIMS.