Gut Instincts: The Gut Microbiome-Cardiovascular Inflammation Axis

Kawasaki Disease (KD), a vasculitis syndrome with a predilection for the coronary arteries, is the leading cause of acquired heart disease in children in developed nations.Though KD can give rise to devastating sequelae, including myocardial infarction, cardiac arrhythmia, myocarditis, coronary artery aneurysm, and sudden cardiac death, the underlying cause remains unknown.In this issue of Circulation Research, Jena et al 1 elucidate the role of the gut microbiome in the pathogenesis of KD vasculitis and identify metabolites produced by specific intestinal commensals that may protect against the vascular inflammation seen in KD.KD is most prevalent among children of Asian descent, indicating some component of genetic susceptibility.2 KD also demonstrates seasonality and epidemicity, however, implicating potential infectious etiologies.3 Most recently, multiple studies comparing rates of KD diagnosis before and during the COVID-19 pandemic observed marked decreases (~30%) coincident with periods of masking and school closures in the United States and Japan.4,5 Even so, prior investigations into various bacterial and viral culprits, from staphylococci to adenovirus, have failed to identify any single pathogen as a trigger for the inflammatory cascade that defines KD. 2 Since several symptoms of KD, including lymphadenopathy and oropharyngeal erythema, mimic hallmarks of common pediatric diseases, some patients are treated with antibiotics as a first course of action.Unfortunately, these antimicrobials are ineffective in treating KD, and have even been associated with worse outcomes.6 Antibiotics can impact the composition of gut microbiota by reducing beneficial bacteria and disrupting the integrity of the mucosal epithelial barrier, alterations that have been associated with increased risk of cardiovascular disease.7 These effects may also be implicated in KD.To assess the link between gut microbiota and cardiovascular inflammation in KD, Jena et al simulate KD in mice via intraperitoneal injection of Lactobacillus casei cell wall extract (LCWE).