Unraveling the gut: the pivotal role of intestinal mechanisms in Kawasaki disease pathogenesis

Front Immunol. 2024 Nov 26:15:1496293. doi: 10.3389/fimmu.2024.1496293. eCollection 2024.

Abstract

Kawasaki disease (KD), an acute systemic vasculitis that primarily affects children under 5 years of age, is the leading cause of acquired heart disease in this age group. Recent studies propose a novel perspective on KD's etiology, emphasizing the gastrointestinal (GI) tract, particularly the role of gut permeability. This review delves into how disruptions in gut barrier function trigger systemic inflammatory responses, exacerbate vascular inflammation, and contribute to coronary artery aneurysms. Evidence suggests that children with KD often exhibit increased gut permeability, leading to an imbalance in gut immunity and subsequent gut barrier damage. These changes impact vascular endothelial cells, promoting platelet aggregation and activation, thereby advancing severe vascular complications, including aneurysms. Additionally, this review highlights the correlation between GI symptoms and increased resistance to standard treatments like intravenous immunoglobulin (IVIG), indicating that GI involvement may predict therapeutic outcomes. Advocating for a new paradigm, this review calls for integrated research across gastroenterology, immunology, and cardiology to examine KD through the lens of GI health. The goal is to develop innovative therapeutic interventions targeting the intestinal barrier, potentially revolutionizing KD management and significantly improving patient outcomes.

Keywords: Kawasaki disease; coronary artery aneurysms; gut microbiota; gut permeability; intravenous immunoglobulin resistance; platelet activation; short-chain fatty acids; systemic vasculitis.

Publication types

  • Review

MeSH terms

  • Animals
  • Gastrointestinal Microbiome / immunology
  • Humans
  • Immunoglobulins, Intravenous / therapeutic use
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Intestines / immunology
  • Mucocutaneous Lymph Node Syndrome* / etiology
  • Mucocutaneous Lymph Node Syndrome* / immunology
  • Permeability

Substances

  • Immunoglobulins, Intravenous

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Medical and Health Research Science and Technology Plan Project of Zhejiang Province (2024KY554), the Social Development Technology Plan Project of Zhuhai City (2420004000130) and the Clinical Research Promotion Project of Zhuhai People's Hospital (2023LCTS-19).