. 2025 Apr 11;136(8):e53-e72.

doi: 10.1161/CIRCRESAHA.124.325079. Epub 2025 Mar 3.

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

Prasant K Jena^{1

2}, Daiko Wakita^{1

2}, Angela C Gomez^{1

2}, Thacyana T Carvalho^{1

2}, Asli E Atici^{1

2}, Emily Aubuchon^{1

2}, Meena Narayanan^{1

2}, Youngho Lee^{1

2}, Michael C Fishbein³, Yoshihiro Takasato^{4

5}, Yosuke Kurashima^{5

6}, Hiroshi Kiyono^{5

6}, Patrice D Cani^{7

8

9}, Willem M de Vos^{10

11}, David M Underhill^{12

13}, Suzanne Devkota^{12

13

14}, Shuang Chen^{1

2

12}, Kenichi Shimada^{1

2

12}, Timothy R Crother^{1

2

12}, Moshe Arditi^{1

2

12

15}, Magali Noval Rivas^{1

2

12}

Affiliations

¹ Division of Infectious Diseases and Immunology, Department of Pediatrics, Guerin Children's at Cedars-Sinai Medical Center, Los Angeles, CA (P.K.J., D.W., A.C.G., T.T.C., A.E.A., E.A., M.N., Y.L., S.C., K.S., T.R.C., M.A., M.N.R.).
² Department of Biomedical Sciences, Infectious and Immunologic Diseases Research Center, (P.K.J., D.W., A.C.G., T.T.C., A.E.A., E.A., M.N., Y.L., S.C., K.S., T.R.C., M.A., M.N.R.), Cedars-Sinai Medical Center, Los Angeles, CA.
³ Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA (M.C.F.).
⁴ Department of Allergy, Allergy and Immunology Center, Aichi Children's Health and Medical Center, Obu, Japan (Y.T.).
⁵ Division of Mucosal Immunology, IMSUT Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Japan (Y.T., Y.K., H.K.).
⁶ Department of Innovative Medicine, Graduate School of Medicine, Chiba University, Japan (Y.K., H.K.).
⁷ Louvain Drug Research Institute, Metabolism and Nutrition Research Group (P.D.C.), UCLouvain, Université catholique de Louvain, Brussels, Belgium.
⁸ Institute of Experimental and Clinical Research (P.D.C.), UCLouvain, Université catholique de Louvain, Brussels, Belgium.
⁹ WELBIO-Walloon Excellence in Life Sciences and BIOtechnology, WELBIO Department, WEL Research Institute, Wavre, Belgium (P.D.C.).
¹⁰ Laboratory of Microbiology, Wageningen University, the Netherlands (W.M.d.V.).
¹¹ Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Finland (W.M.d.V.).
¹² Department of Biomedical Sciences (D.M.U., S.D., S.C., K.S., T.R.C., M.A., M.N.R.), Cedars-Sinai Medical Center, Los Angeles, CA.
¹³ F. Widjaja Inflammatory Bowel Disease Institute (D.M.U., S.D.), Cedars-Sinai Medical Center, Los Angeles, CA.
¹⁴ Human Microbiome Research Institute (S.D.), Cedars-Sinai Medical Center, Los Angeles, CA.
¹⁵ Smidt Heart Research Institute (M.A.), Cedars-Sinai Medical Center, Los Angeles, CA.

PMID: 40026151
PMCID: PMC11985309 (available on 2026-04-11)
DOI: 10.1161/CIRCRESAHA.124.325079

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

Prasant K Jena et al. Circ Res. 2025.

. 2025 Apr 11;136(8):e53-e72.

doi: 10.1161/CIRCRESAHA.124.325079. Epub 2025 Mar 3.

Authors

Affiliations

¹ Division of Infectious Diseases and Immunology, Department of Pediatrics, Guerin Children's at Cedars-Sinai Medical Center, Los Angeles, CA (P.K.J., D.W., A.C.G., T.T.C., A.E.A., E.A., M.N., Y.L., S.C., K.S., T.R.C., M.A., M.N.R.).
² Department of Biomedical Sciences, Infectious and Immunologic Diseases Research Center, (P.K.J., D.W., A.C.G., T.T.C., A.E.A., E.A., M.N., Y.L., S.C., K.S., T.R.C., M.A., M.N.R.), Cedars-Sinai Medical Center, Los Angeles, CA.
³ Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA (M.C.F.).
⁴ Department of Allergy, Allergy and Immunology Center, Aichi Children's Health and Medical Center, Obu, Japan (Y.T.).
⁵ Division of Mucosal Immunology, IMSUT Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Japan (Y.T., Y.K., H.K.).
⁶ Department of Innovative Medicine, Graduate School of Medicine, Chiba University, Japan (Y.K., H.K.).
⁷ Louvain Drug Research Institute, Metabolism and Nutrition Research Group (P.D.C.), UCLouvain, Université catholique de Louvain, Brussels, Belgium.
⁸ Institute of Experimental and Clinical Research (P.D.C.), UCLouvain, Université catholique de Louvain, Brussels, Belgium.
⁹ WELBIO-Walloon Excellence in Life Sciences and BIOtechnology, WELBIO Department, WEL Research Institute, Wavre, Belgium (P.D.C.).
¹⁰ Laboratory of Microbiology, Wageningen University, the Netherlands (W.M.d.V.).
¹¹ Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Finland (W.M.d.V.).
¹² Department of Biomedical Sciences (D.M.U., S.D., S.C., K.S., T.R.C., M.A., M.N.R.), Cedars-Sinai Medical Center, Los Angeles, CA.
¹³ F. Widjaja Inflammatory Bowel Disease Institute (D.M.U., S.D.), Cedars-Sinai Medical Center, Los Angeles, CA.
¹⁴ Human Microbiome Research Institute (S.D.), Cedars-Sinai Medical Center, Los Angeles, CA.
¹⁵ Smidt Heart Research Institute (M.A.), Cedars-Sinai Medical Center, Los Angeles, CA.

PMID: 40026151
PMCID: PMC11985309 (available on 2026-04-11)
DOI: 10.1161/CIRCRESAHA.124.325079

Abstract

Background: Alterations in the intestinal microbiota contribute to the pathogenesis of various cardiovascular disorders, but how they affect the development of Kawasaki disease (KD) an acute pediatric vasculitis, remains unclear.

Methods: We used the Lactobacillus casei cell wall extract (LCWE) murine model of KD vasculitis to assess the contribution of the intestinal microbiota to the development of vascular inflammation. We evaluated the severity of vasculitis in microbiota-depleted mice. 16S rRNA gene sequencing was used to characterize the fecal microbiome composition of LCWE-injected mice. Some groups of mice were orally treated with selected live or pasteurized bacteria, short-chain fatty acids, or Amuc_1100, the Toll-like receptor 2 signaling outer membrane protein from Akkermansia muciniphila, and their impact on vasculitis development was assessed.

Results: We report that depleting the gut microbiota reduces the development of cardiovascular inflammation in a murine model mimicking KD vasculitis. The development of cardiovascular lesions was associated with alterations in the intestinal microbiota composition and, notably, a decreased abundance of Akkermansia muciniphila and Faecalibacterium prausnitzii. Oral supplementation with either of these live or pasteurized individual bacteria or with short-chain fatty acids produced by them attenuated cardiovascular inflammation, as reflected by decreased local immune cell infiltrations. Treatment with Amuc_1100 also reduced the severity of vascular inflammation.

Conclusions: This study reveals an underappreciated gut microbiota-cardiovascular inflammation axis in KD vasculitis pathogenesis and identifies specific intestinal commensals that regulate vasculitis in mice by producing metabolites or via extracellular proteins capable of enhancing and supporting gut barrier function.

Keywords: coronary aneurysm; coronary vessels; gastrointestinal microbiome; interleukin-1; vasculitis.

PubMed Disclaimer

Conflict of interest statement

W.M. de Vos and P.D. Cani are inventors of patent applications dealing with the use of specific bacteria and components in the treatment of different diseases. W.M. de Vos and P.D. Cani have cofounded The Akkermansia Company SA, which is commercializing Akkermansia muciniphila, and have stocks in this start-up company. W.M. de Vos cofounded Caelus Health. P.D. Cani cofounded Enterosys. The other authors report no conflicts.

Update of

The intestinal microbiota contributes to the development of immune-mediated cardiovascular inflammation and vasculitis in mice.
Jena PK, Wakita D, Gomez AC, Carvalho TT, Atici AE, Narayanan M, Lee Y, Fishbein MC, Cani PD, de Vos WM, Underhill DM, Devkota S, Chen S, Shimada K, Crother TR, Arditi M, Rivas MN. Jena PK, et al. bioRxiv [Preprint]. 2024 Jun 2:2024.05.28.596258. doi: 10.1101/2024.05.28.596258. bioRxiv. 2024. Update in: Circ Res. 2025 Apr 11;136(8):e53-e72. doi: 10.1161/CIRCRESAHA.124.325079. PMID: 38853964 Free PMC article. Updated. Preprint.

Comment in

Gut Instincts: The Gut Microbiome-Cardiovascular Inflammation Axis.
Dalman JM, Blaustein ER, van Solingen C. Dalman JM, et al. Circ Res. 2025 Apr 11;136(8):806-808. doi: 10.1161/CIRCRESAHA.125.326363. Epub 2025 Apr 10. Circ Res. 2025. PMID: 40208926 No abstract available.

References

1. McCrindle BW, Rowley AH, Newburger JW, Burns JC, Bolger AF, Gewitz M, Baker AL, Jackson MA, Takahashi M, Shah PB, et al. Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association. Circulation. 2017;135:e927–e999. doi: 10.1161/cir.0000000000000484 - DOI - PubMed
1. Rowley AH, Shulman ST. The Epidemiology and Pathogenesis of Kawasaki Disease. Front Pediatr 2018;6:581–-584. - PMC - PubMed
1. Noval Rivas M, Arditi M. Kawasaki disease: pathophysiology and insights from mouse models. Nat Rev Rheumatol 2020;16:391–405. doi: 10.1038/s41584-020-0426-0 - DOI - PMC - PubMed
1. Rowley AH. Is Kawasaki disease an infectious disorder? Int J Rheum Dis 2018;21:20–25. doi: 10.1111/1756-185x.13213 - DOI - PMC - PubMed
1. Brown TJ, Crawford SE, Cornwall ML, Garcia F, Shulman ST, Rowley AH. CD8 T lymphocytes and macrophages infiltrate coronary artery aneurysms in acute Kawasaki disease. J Infect Dis 2001;184:940–-943. - PubMed

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions

Supplementary concepts

Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Medical
- MedlinePlus Health Information

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Update of

Comment in

References

MeSH terms

Substances

Supplementary concepts

Grants and funding

LinkOut - more resources

Full Text Sources

Medical