Artif Cells Nanomed Biotechnol. 2026 Dec;54(1):305-320. doi: 10.1080/21691401.2026.2700919. Epub 2026 Jul 9.
ABSTRACT
Kawasaki disease (KD) is a systemic vasculitis in children primarily affecting the coronary arteries, and studies suggest that the gut microbiota may be involved in KD pathogenesis, inflammatory responses, and immune regulation. This study employed an integrative multi-omics strategy to systematically investigate gut microbiota-metabolite interactions in KD. Key molecular targets were identified using network-based analyses and machine learning models, with Mendelian randomization providing causal validation. Single-cell transcriptomics and molecular docking further elucidated immune cell interactions and metabolite-protein binding, highlighting critical regulatory pathways. We identified SELP as a core molecular target in KD, predominantly expressed in platelets and involved in immune and inflammatory responses. Gut microbiota-derived metabolites, including palmitoylethanolamide, pantothenic acid, and 1-O-caffeoylglycerol, may regulate immune cell interactions via the RESISTIN signalling pathway. Altered abundances of microbial taxa such as Bacteroides, Parabacteroides, and Bifidobacterium suggest their potential role in inflammation modulation. Activation of IL-17, TNF, MAPK, and PI3K-Akt pathways further contributes to disease progression, highlighting the microbiota-metabolite-SELP axis as a potential therapeutic target in KD. These findings lay the groundwork for subsequent in vitro and in vivo studies, advancing the development of microbiome-based intervention strategies.
PMID:42422999 | DOI:10.1080/21691401.2026.2700919