Multi-omics analyses reveal significant differences in the gut microbiota and metabolites in children with Kawasaki disease in Northwest China.

BACKGROUND: Kawasaki disease (KD) is a systemic vasculitis characterized by mucocutaneous lymph node syndrome and aberrant immune activation. Previous studies have indicated substantial disruptions in the gut microbiota during the acute phase of KD. However, the detailed characteristics of the gut microbiota and metabolome in children with KD, as well as their clinical relevance, remain poorly understood.

METHODS: 31 children with KD (KDs) and age/sex-matched healthy controls (HCs) were enrolled to collect their fecal and blood samples. Shotgun metagenomic sequencing and untargeted metabolomic analyses were conducted on these samples.

RESULTS: Significant reductions in alpha diversity and microbial richness were observed in the gut microbiota of KDs at both species and genus levels. Pathogenic species including Enterococcus avium, Streptococcus peroris and Clostridioides difficile were significantly abundant in the KDs group, while beneficial species containing Faecalibacterium prausnitzii, Anaerostipes hadrus, Akkermansia muciniphila, Eubacterium hallii, Agathobaculum butyriciproducens, Ruminococcus bicirculans, and Roseburia intestinalis were markedly decreased. A total of 49 metabolic pathways were differentially enriched between the two groups, with 22 pathways including nucleotide, carbohydrate, energy, and amino acid metabolism being abundant in KDs, while the other 27 pathways were enriched in HCs. For metabolites, both fecal and blood metabolomes exhibited significant alterations. Notably, fecal metabolites including indole, L-tryptophan, L-lactic acid, 5-HETE, indol-3-acetamid, tetraethylammonium and dopaquinone were elevated in KDs, whereas butyrate, methylxanthine, phosphocholine, methylhistidine, ADP-ribose, vitamin A acid, and chenodeoxycholic acid were reduced. In plasma, cholesterol, phosphocholine, porphobilinogen, pantothenate, cortisol, bile acids and related compounds were enriched in KDs, while amino acids, indole and tryptamine derivatives, nucleotides, nucleic acids, and sugar metabolites were more abundant in HCs.

CONCLUSIONS: This study represents the first systematic multi-omics investigation of KD in a pediatric population from Northwest China. It establishes a foundational resource characterizing the gut microbiome and metabolome in KD, offering novel biological insights, suggesting potential therapeutic targets, and supporting further mechanistic and clinical research.