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Gut microbiota metabolic characteristics in coronary artery disease patients with hyperhomocysteine
Ran Tian1, Hong-Hong Liu1, Si-Qin Feng1
1Department of Cardiology, Peking Union Medical College Hospital, Beijing, 100730, P. R. China.
Insights
Elevated homocysteine (HHcy) in coronary artery disease (CAD) patients is linked to increased atherosclerosis. This is associated with altered gut microbiota, BHMT, and TMAO metabolism, highlighting potential therapeutic targets.
Area of Science:
- Cardiovascular Research
- Metabolomics
- Microbiome Research
Background:
- Hyperhomocysteinemia (HHcy) is a known risk factor for coronary artery disease (CAD).
- The gut microbiota's role in HHcy and its connection to CAD remains underexplored.
- Metabolic pathways involving gut microbiota share metabolites with homocysteine (Hcy) metabolism.
Purpose of the Study:
- To investigate the association between HHcy and gut microbiota in patients with CAD.
- To identify metabolic signatures and microbial changes related to HHcy in CAD patients.
- To explore the link between HHcy, gut microbiota, and atherosclerotic burden.
Main Methods:
- Multi-omics analyses including LC/MS/MS for serum metabolites and 16S rRNA sequencing for fecal microbiota.
- Recruitment of 105 CAD patients and 14 healthy controls from a single medical center in Beijing.
- Classification of participants into CAD, CAD with HHcy, and healthy control (HC) groups based on diagnosis and Hcy levels.
Main Results:
- Significant differences in metabolic profiles were observed between CAD and CAD with HHcy groups.
- CAD patients with HHcy exhibited a greater atherosclerotic burden, linked to BHMT and TMAO metabolites.
- Dimethylglycine (DMG) positively correlated with serum total Hcy (tHcy); TMAO and trimethylysine (TML) associated with higher atherosclerotic burden.
- Clostridium cluster IV and Butyricimonas were enriched in CAD patients with elevated tHcy.
Conclusions:
- Elevated tHcy in CAD patients correlates with increased atherosclerotic burden.
- Impaired Hcy metabolism and cardiovascular risk are associated with BHMT and TMAO metabolites.
- Gut microbiota dysbiosis plays a role in the relationship between HHcy, CAD, and cardiovascular risk.
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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