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Gut microbiota metabolic characteristics in coronary artery disease patients with hyperhomocysteine

  • Microbial Pathogenesis and Host-Microbe Interaction
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Abstract

Hyperhomocysteine (HHcy) is known as a risk factor for coronary artery disease (CAD). Despite the knowledge that gut microbiota related metabolism pathway shares metabolites with that of Hcy, little has been shown concerning the association between HHcy and gut microbiota. To explore their relationship in the context of CAD, 105 patients and 14 healthy controls were recruited from one single medical center located in Beijing, China. Their serum and fecal samples were collected, with multi-omics analyses performed via LC/MS/MS and 16S rRNA gene V3-V4 region sequencing, respectively. Participants from the prospective cohort were divided into CAD, CAD & HHcy and healthy controls (HC) groups based on the diagnosis and serum Hcy concentration. The results revealed significant different metabolic signatures between CAD and CAD & HHcy groups. CAD patients with HHcy suffered a heavier atherosclerotic burden compared to CAD patients, and the difference was closely associated to betaine-homocysteine S-methyltransferase (BHMT)-related metabolites and trimethylamine N-oxide (TMAO)-related metabolites. Dimethylglycine (DMG) exhibited a strong positive correlation with serum total Hcy (tHcy), and TMAO and trimethylysine (TML) were associated with heavier atherosclerotic burden. Multiple other metabolites were also identified to be related to distinct cardiovascular risk factors. Additionally, Clostridium cluster IV and Butyricimonas were enriched in CAD patients with elevated tHcy. Our study suggested that CAD patients with elevated tHcy were correlated with higher atherosclerotic burden, and the impaired Hcy metabolism and cardiovascular risk were closely associated with BHMT-related metabolites, TMAO-related metabolites and impaired gut microbiota homeostasis.

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Acknowledgements

This work was supported by the Beijing Natural Science Foundation (grant no. L202046), the National Natural Science Foundation (grant no. 82170486) and the fellowship of China Postdoctoral Science Foundation (2021TQ0050).

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiology, Peking Union Medical College Hospital, Beijing, 100730, P. R. China

    Ran Tian, Hong-Hong Liu, Si-Qin Feng, Yu-Xiong Chen, Hui Wang & Shu-Yang Zhang

  2. School of Medicine, Tsinghua University, Beijing, 100084, P. R. China

    Yi-Fei Wang & Yi-Yang Wang

  3. Department of Cardiology, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, 102218, P. R. China

    Yi-Fei Wang

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  1. Ran Tian
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Contributions

R. Tian and SY. Zhang designed and coordinated the study. HH. Liu, SQ. Feng, YF. Wang and YY. Wang were in charge of patient recruitment, sample collection. HH. Liu and SQ. Feng carried out the bioinformatic analyses of metagenomic and metabolomics data. YF. Wang completed the figure drawing and editing. YX. Chen, YY. Wang and H. Wang helped the supplementary experiment and technical assistance. R. Tian and HH. Liu wrote the manuscript. SY. Zhang revised the manuscript. All authors read and approved the final manuscript.

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Correspondence to Shu-Yang Zhang.

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The study was approved by local ethics committee of Peking Union Medical College Hospital (JS-1195) and informed consent was obtained from all study participants.

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The authors declare no competing interests.

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The data set supporting the results of this article has been deposited in the Sequence Read Archive (SRP) under BioProject accession code SRP167862.

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Tian, R., Liu, HH., Feng, SQ. et al. Gut microbiota metabolic characteristics in coronary artery disease patients with hyperhomocysteine. J Microbiol. 60, 419–428 (2022). https://doi.org/10.1007/s12275-022-1451-2

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  • DOI: https://doi.org/10.1007/s12275-022-1451-2

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