Gut microbiota, inflammatory cytokines, and Kawasaki disease: a Mendelian randomization study and mediation analysis

Ji-Gan Wang1, Hui-Hong Dou2, Qiong-You Liang2

  • 1Department of Pediatrics, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Guangxi Clinical Research Center for Pediatric Diseases, Nanning, China. wangjigan@163.com.

Pediatric Research
|February 10, 2025
PubMed
Abstract

Insights

This study reveals that gut bacteria influence Kawasaki disease (KD) risk, with some microbes increasing or decreasing susceptibility. Specific inflammatory cytokines mediate these effects, highlighting a gut microbiome connection to KD.

Area of Science:

  • Microbiome research
  • Immunology
  • Pediatric disease

Background:

  • Kawasaki disease (KD) is an acute febrile vasculitis affecting young children.
  • The etiology of KD remains unclear, but the gut microbiome and inflammatory responses are implicated.
  • Understanding the interplay between gut microbiota and inflammatory cytokines in KD is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the causal relationship between gut microbiota composition and Kawasaki disease (KD).
  • To examine the association between inflammatory cytokines and KD.
  • To determine if inflammatory cytokines mediate the influence of gut microbiota on KD development.

Main Methods:

  • Mendelian randomization analysis was employed to assess causal effects.
  • Inverse-variance weighted method was utilized for statistical analysis.
  • Mediation analysis explored the role of cytokines in the gut microbiota-KD pathway.

Main Results:

  • Causal links were established between 20 gut microbial types and KD.
  • Francisellales significantly increased KD risk (OR=27.82), while Fusobacteriaceae showed a protective effect (OR=0.0424).
  • Adenosine deaminase exhibited a protective association with KD (OR=0.7447), whereas Fractalkine was linked to increased risk (OR=2.0448).
  • Interleukin-10 receptor subunit beta and Interleukin-20 were identified as mediators in the gut microbiota-KD relationship.

Conclusions:

  • Gut microbiota composition causally influences Kawasaki disease risk.
  • Specific inflammatory cytokines mediate the impact of gut microbes on KD pathogenesis.
  • Targeting the gut microbiome and associated inflammatory pathways may offer novel therapeutic strategies for KD.

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