Intestinal Microbiota Contributes to the Development of Cardiovascular Inflammation and Vasculitis in Mice

Area of Science:

• Microbiology
• Immunology
• Cardiovascular Research

Background:

• Intestinal microbiota alterations are linked to cardiovascular disorders.
• The specific role of gut microbiota in Kawasaki disease (KD) pathogenesis, a pediatric vasculitis, is not well understood.

Purpose of the Study:

• To investigate the contribution of the intestinal microbiota to the development of vascular inflammation in a murine model of KD.
• To identify specific gut bacteria and their products that may modulate KD vasculitis.

Main Methods:

• Utilized the Lactobacillus casei cell wall extract (LCWE) murine model of KD vasculitis.
• Assessed vasculitis severity in microbiota-depleted mice and characterized fecal microbiome using 16S rRNA gene sequencing.
• Administered oral treatments including live/pasteurized bacteria, short-chain fatty acids, and Amuc_1100 (from Akkermansia muciniphila) to evaluate their impact.

Main Results:

• Depleting the gut microbiota reduced cardiovascular inflammation in the KD mouse model.
• Cardiovascular lesions correlated with altered microbiota, specifically decreased Akkermansia muciniphila and Faecalibacterium prausnitzii.
• Supplementation with these bacteria, their short-chain fatty acids, or Amuc_1100 attenuated vascular inflammation and immune cell infiltration.

Conclusions:

• A gut microbiota-cardiovascular inflammation axis is implicated in KD pathogenesis.
• Specific commensal bacteria, their metabolites, and extracellular proteins play a role in regulating vasculitis by supporting gut barrier function.