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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