Table 2.
Gut microbiota derived metabolites and cardiovascular health and disease
| Metabolite | Substrate | Gene/enzyme | Bacteria | Biological Effects | Host target | Disease | Ref. |
|---|---|---|---|---|---|---|---|
| esculetin | esculin | NA | Enterococcus faecalis, Selenomonas ruminantium 2358, et al. | ↑NO | aortic endothelial cell | atherosclerosis | 56-57 |
| protocatechuic acid | anthocyanin | NA | NA | ↓miR-10b, ↑ABCA1 and ABCG1 | macrophage | atherosclerosis | 58-61 |
| urolithin | ellagitannin | NA | Gordonibacter urolithinfaciens sp. nov. and Bifidobacterium seudocatenulatum INIA P815 | Inhibiting endothelial cell migration, ↓ chemokine ligand 2 and IL-8, ↑ eNOS | endothelial cell | atherosclerosis | 62-69 |
| enterolactone | phytolignan | NA | NA | ↓lipid peroxidation | NA | heart disease- and CVD-related mortality | 70-71 |
| TMAO | phosphatidylcho-line, choline, carnitine, buytrobetaine, betaine, trimethyllysine, valerobetaine, ergothioneine | cutC/D, yeaW/X, Grdh, egtA, egtB, egtC, egtD, egtE, torA | Diverse | ↑CD36, SR-A1 ↓Cyp7a1 and Cyp27a1, ↑MAPK, NFκB, NLRP3 signaling ↑Ca2+ release |
macrophage, endothelial cell, platelet | atherosclerosis, thrombosis | 80-110 |
| indoxyl sulfate | tryptophan | NA | Lactobacillus, Bifidobacterium longum, Bacteroides fragilis, Parabacteroides distasonis, Clostridium bartlettii and Eubacterium hallii | ↑oxidative stress, ↓nitric oxide, ↑TNFα |
monocyte, vascular endothelial cells | adverse cardiac event | 114-124 |
| p-cresyl sulfate | tyrosine | Tyrosine phenol-lyase (EC 4.1.99.2.),tyrosine transaminase (EC 2.6.1.5.) or by aromatic-amino-acid transaminase (EC 2.6.1.57.), phenylalanine dehydrogenase (EC 1.4.1.20.),p-hydroxyphenylpyruvate oxidase,p-hydroxyphenylacetate decarboxylase | Bacteroidaceae, Bifidobacteriaceae, Clostridiaceae, Enterobacteriaceae, Enterococcaceae, Eubacteriaceae, Fusobacteriaceae, Lachnospiraceae, Lactobacillaceae, Porphyromonadaceae, Staphylococcaceae, Ruminococcaceae, Veillonellaceae | ↑ NADPH oxidase, ↑ROS, |
cardiomyocyte | cardiovascular event and all-cause mortality in elderly hemodialysis patients | 126-128 |
| phenylacetylglutamine | phenylalanine | amino transferase (Aat), PorA, | Clostridium sporogenes, | NA | NA | Cardiac event | 133 |
NA, not available; CVD, cardiovascular disease. ↑ ↓ increases or decreases compared with control, respectively.