Gut Commensal Bacteroides thetaiotaomicron Promote Atherothrombosis via Regulating L-Tryptophan Metabolism

Honghong Liu; Siqin Feng; Muyun Tang; Ran Tian; Shuyang Zhang

doi:10.31083/j.rcm2511395

Gut Commensal Bacteroides thetaiotaomicron Promote Atherothrombosis via Regulating L-Tryptophan Metabolism

Rev Cardiovasc Med. 2024 Nov 7;25(11):395. doi: 10.31083/j.rcm2511395. eCollection 2024 Nov.

Authors

Honghong Liu^{1

2}, Siqin Feng^{1

2}, Muyun Tang^{1

2}, Ran Tian^{1

2}, Shuyang Zhang^{1

2}

Affiliations

¹ Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 100730 Beijing, China.
² State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 100730 Beijing, China.

Abstract

Background: Coronary thrombosis events continue to be the leading cause of morbidity and mortality worldwide. Recently, emerging evidence has highlighted the role of gut microbiota in cardiovascular disease, but few studies have systematically investigated the gut microbiota variation associated with atherothrombosis.

Methods: We conducted multi-omics analysis (metagenomics sequencing and serum metabolomics) on 146 subjects from Peking Union Medical College Hospital-Coronary Artery Disease (PUMCH-CAD) cohort. We analyzed the key strains and metabolic pathways related to coronary artery disease (CAD) development, explored the bacterial functional pathway which contributes to atherothrombosis at strain level in depth. Single strain colonization procedures on germ free mice demonstrated the promotion of platelet activation and thrombotic phenotypes of the disordered gut microbiota.

Results: Gut microbiome and serum metabolome shifts were apparent in cases of CAD progression, Bacteroides spp. disturbed the development of CAD by participating in lipopolysaccharide (LPS), menaquinone and methanogenesis pathways. Particularly, coronary thrombosis is characterized by increased circulatory levels of L-tryptophan, which correlate with Bacteroides thetaiotaomicron that has enriched biosynthetic potential. In germ free mice we demonstrate that Bacteroides thetaiotaomicron colonization could induce thrombosis, aggravate platelet hyperreactivity and augment fecal levels of L-tryptophan.

Conclusions: The disordered gut microbiota of CAD contributed to the occurrence and development of atherothrombosis. The key members of the bacterial and metabolic features may become biomarkers for predicting the cardiovascular thrombosis event. Targeting the microbial pathway may have the potential to reduce the incidence of cardiovascular disorders.

Clinical trial registration: ChiCTR2000033897, https://www.chictr.org.cn/showproj.html?proj=55023.

Keywords: Bacteroides thetaiotaomicron; L-tryptophan; atherothrombosis; coronary artery disease; gut microbiota; myocardial infarction.

Grants and funding

This work was supported by National Natural Science Foundation of China (grant 82170486 and 81670329 to SY.Z.) (grant 82300382 to HH.L.); National Key Research and Development Program of China (grant 2022YFC2703100 to SY.Z.); China Postdoctoral Science Foundation (2021TQ0050 to HH. L.).