# Role of intestinal microbiome and gut permeability in the development of Kawasaki Disease vasculitis

> **NIH NIH R01** · CEDARS-SINAI MEDICAL CENTER · 2022 · $437,500

## Abstract

PROJECT ABSTRACT
Kawasaki disease (KD) is an acute febrile illness/systemic vasculitis of unknown etiology that predominantly
afflicts young children, causes coronary artery abnormalities and aneurysms (CAA), and could potentially result
in long-term cardiovascular sequelae and even death. KD vasculitis is the leading cause of acquired heart
disease among children in the US. CAA develop in 25% of untreated children with KD, leading to ischemic
heart disease and myocardial infarction. While Intravenous immunoglobulin (IVIG) treatment lowers the risk of
CAA to 5%, up to 25% of KD patients are IVIG-resistant and have a greater risk for CAA. Therefore, discovery
of more effective treatments to prevent the cardiovascular complications of KD vasculitis is a high priority in
pediatric and cardiovascular research. The intestinal microbiome is an integral part of our physiology and
intestinal dysbiosis influences the development of a number of immunological and non-immunological
diseases, including cardiovascular diseases. In preliminary studies, we discovered striking new evidence that
intestinal microbiota, gut permeability, and dysregulated mucosal immune responses play a key role in the
development of coronary arteritis and aneurysm formation in KD using a well-established KD vasculitis mouse
model. Based on our preliminary data, we hypothesize that intestinal dysbiosis and increased gut permeability
concomitantly occur during KD and play a crucial role in modulating immune responses significantly
contributing to the cardiovascular lesions associated with KD. These events will result in commensal
microbiota translocation and/or bacterial/fungal PAMPs as well as increased gut permeability of metabolites,
and secretory IgA into blood circulation and may play an important role in modulating and fine-tuning systemic
and local immune responses helping drive the immunopathology and fuel the development of KD lesions.
Deciphering the mechanisms by which the intestinal commensal micro and mycobiome and increased gut
permeability affect the development of cardiovascular lesions of KD could provide a novel therapeutic target for
intervention. To test this hypothesis, we propose to determine how compositional alterations of the intestinal
commensals influence murine KD vasculitis pathology (Aim 1). We will investigate the role of increased
intestinal permeability and determine if its prevention has therapeutic value during murine KD vasculitis. (Aim
2). We will characterize the role of secretory IgA leaking from the gut in promoting the development of
cardiovascular lesions in KD vasculitis model (Aim 3). Clinical data suggest that children with KD frequently
have a leaky gut and more than 80% receive microbiome altering antibiotics in the week prior to KD diagnosis.
Therefore, this proposal has a very high translational potential given that specific manipulation of the
commensal microbiota is a research area with high therapeutic promises. Understanding the rol...

## Key facts

- **NIH application ID:** 10310487
- **Project number:** 5R01HL139766-05
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **Principal Investigator:** Magali Noval Rivas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $437,500
- **Award type:** 5
- **Project period:** 2018-01-01 → 2024-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10310487

## Citation

> US National Institutes of Health, RePORTER application 10310487, Role of intestinal microbiome and gut permeability in the development of Kawasaki Disease vasculitis (5R01HL139766-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10310487. Licensed CC0.

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