When a child presents with a stubborn high fever, an angry rash and red eyes, the pediatrician’s impulse might be to prescribe antibiotics, since such symptoms can indicate a serious infection that requires swift treatment. But for patients with Kawasaki disease, a rare pediatric vasculitis that can masquerade as a bacterial infection, prescribing antibiotics before obtaining a definitive diagnosis is a risky gamble.  

The onset of Kawasaki disease is sudden and confounding. And recent research reveals a surprising twist: Antibiotics aren’t just ineffective at treating Kawasaki disease—they may make things worse. 

"Antibiotic treatment may help children with bacterial infections but not patients with Kawasaki disease. Antibiotics compromises their gut microbiome, which plays an important role in protecting children from long-term complications such as cardiac dysfunction, arrythmias and even death," said Magali Noval Rivas, PhD, a cellular and molecular immunologist at Cedars-Sinai.

In studying the gastrointestinal system for more than 10 years, Noval Rivas has discovered that imbalances in gut microbiota, called dysbiosis, also fuel more common pediatric immune conditions, including allergies and asthma.

Noval Rivas recently co-authored a preclinical study in Circulation Research, showing that altering the gut microbiome by introducing beneficial bacteria could help stall disease progression and improve cardiac abnormalities in patients with Kawasaki disease.

"If we're able to grow specific anti-inflammatory bacteria in the laboratory and deliver them back to the patient, it may help reduce intestinal dysbiosis and promote intestinal barrier functions—and that can be relevant for several inflammatory diseases, not just Kawasaki disease," said Moshe Arditi, MD, executive vice chair of the Department of Pediatrics for Research, part of Cedars-Sinai Guerin Children’s, who works closely with Noval Rivas.

The gut microbiome is home to trillions of diverse microorganisms that regulate mucosal barriers and support immune function. This complex ecosystem is established at birth and remains for a lifetime, but it’s constantly in flux. Specific alterations in the intestinal microbiota composition can contribute to a host of inflammatory and metabolic diseases, including Kawasaki disease and cardiovascular disease.

Kawasaki disease, first identified in 1967 by Japanese pediatrician Tomisaku Kawasaki, primarily affects children under 5 years old. The disease is rare in the United States, affecting 18 to 25 per 100,000 children under age 5 annually. It is the leading cause of acquired heart disease in children. The incidence is 10 to 30 times higher in Japan, South Korea, China and Taiwan, suggesting that genetic variation and environmental factors are responsible for this increased risk.

The exact cause of the condition remains unclear, and there is no diagnostic test for the disorder. Clinicians rely on symptoms such as high fever, rash, red eyes, and swollen hands and feet.

The standard treatment for Kawasaki disease is intravenous immunoglobulin (IVIG) therapy, which dramatically reduces the risk of adverse outcomes, including coronary artery disease. However, scientists don’t fully understand how IVIG produces these beneficial effects, and about 20% of children with Kawasaki disease do not respond to IVIG. Without effective treatment, vascular inflammation in Kawasaki disease increases the risk of developing cardiovascular complications that may extend into adolescence and adulthood.

Mounting evidence shows that children who receive antibiotics during the acute phase of Kawasaki disease are less likely to respond to IVIG treatment and more prone to cardiovascular complications.

"Compared to healthy children, patients with Kawasaki disease have an abundance of harmful bacteria in the gut and lower levels of beneficial short-chain fatty acid (SCFA)-producing bacteria, which are protective against the disease," said Arditi, who is the GUESS?/Fashion Industries Guild Chair in Community Child Health at Cedars-Sinai.  

The imbalance of gut microbiota may render children more vulnerable to the disease’s effects and increases the risk of long-term cardiac complications.

In animal models, supplementing SCFAs—molecules produced by beneficial gut bacteria—lowers blood pressure and boosts immune response after myocardial infarction and helps prevent atherosclerosis.

"In the future, treatment for Kawasaki disease may combine IVIG with probiotic approaches such as SCFA-producing bacteria to help manage inflammation and reduce cardiovascular risks," Arditi said.

Noval Rivas' research isn’t limited to Kawasaki disease. Her earlier work in pediatric food allergies and asthma suggests that targeting and manipulating the gut microbiome holds promise for managing different inflammatory conditions.

"Such therapies could involve administering prebiotics and probiotics to promote the growth of beneficial bacteria and help regulate intestinal immune responses," Noval Rivas said.

An earlier work, published in the Journal of Allergy and Clinical Immunology, connects a unique gut microbiota signature with the development of food allergies and suggests that treatment with allergen-specific regulatory T-cells may help suppress the allergic response.

"Since inflammation and gut dysbiosis are key drivers for a variety of diseases, similar strategies may apply to any inflammatory disease linked to reduced levels of SCFAs," said Noval Rivas. "If we can learn to manipulate gut bacteria in specific ways, we might be able to turn the tide on several inflammatory diseases that have long evaded effective treatment."