Role of S-Equol, Indoxyl Sulfate, and Trimethylamine N-Oxide on Vascular Function

Abstract

Gut microbiota have been emerging as important contributors to the regulation of host homeostasis. Accordingly, several substances converted by gut microbiota can have beneficial or adverse effects on human health. Among them, S-equol, which is produced from the isoflavone daidzein in the human and animal gut by certain microbiota, exerts estrogenic and antioxidant activities. Indoxyl sulfate, which is metabolized in the liver from indole converted from dietary tryptophan by bacterial tryptophanases in the colon, is known as a protein-bound uremic toxin. Trimethylamine N-oxide, which is generated via the oxidization of gut microbiota-derived trimethylamine by hepatic flavin monooxygenases, is known as an accelerator of atherosclerosis. The aforementioned gut-derived substances could be potential regulators of systematic tissue/organ function, including the vascular system. Macro- and microvascular complications of cardiovascular and metabolic diseases, including atherosclerosis, hypertension, and diabetes, occur systemically and represent the principal cause of morbidity and mortality. Vascular endothelial and smooth muscle dysfunction play pivotal roles in the development and progression of vasculopathies. We herein review the link between the aforementioned gut-derived substances and endothelial and vascular smooth muscle cell function. This information will provide a conceptual framework that would allow the development of novel preventive and/or therapeutic approaches against vasculopathies.

Endothelial Damage, Inflammation and Immunity in Chronic Kidney Disease

“…The endothelium in CKD patients suffers from a continuous insult causing its activation and injury that may end in a dysfunctional state ( Figure 1 ). The endothelial activation in CKD is attributed to the pulsatile blood flow and disturbed shear stress [ 36 ], accumulation of uremic toxins, such as dimethyl arginines [ 37 , 38 ], indoxyl sulfate (IS) [ 39 , 40 , 41 ], indole-3 acetic acid (IAA) [ 21 , 42 ], kynurenine [ 20 , 43 , 44 ], p-cresol [ 45 , 46 ], trimethylamine-N-oxide (TMAO) [ 41 , 47 ], oxidized low-density lipoprotein (LDL) cholesterol particles [ 48 ], carbamylated lipoproteins [ 49 , 50 ], reactive oxygen species (ROS) [ 39 , 51 , 52 ], advanced glycation end-products (AGEs) [ 53 , 54 ], hyperhomocysteinemia [ 55 , 56 ], hyperphosphatemia [ 57 , 58 ], bacterial lipopolysaccharides or other bacterial products [ 59 , 60 , 61 ], endogenous damage-associated molecules, and proinflammatory cytokines [ 62 , 63 , 64 , 65 , 66 ], which all together constitute the uremic environment.…”

The influence of gut microbiota in cardiovascular diseases—a brief review

“… 18 Blood pressure regulation has generally been linked to the renin-angiotensin system, which involves the angiotensin-converting enzyme (ECA), and although the direct link between hypertension and TMAO has not been fully established, it is known that it prolongs the hypertensive effect of angiotensin II. 28 …”

Role of gut microbiota‐derived metabolites on vascular calcification in CKD

“…S‐equol can protect vasculature against cardiovascular diseases. Thus, S‐equol should have an important role in the field of vascular research 96 . It is thus proposed that the use of oral iron supplements might improve the gut microbiome.…”