Gut microbiota dependant trimethylamine N-oxide and hypertension

Abstract

The human gut microbiota environment is constantly changing and some specific changes influence the host's metabolic, immune, and neuroendocrine functions. Emerging evidence of the gut microbiota's role in the development of cardiovascular disease (CVD) including hypertension is remarkable. There is evidence showing that alterations in the gut microbiota and especially the gut-dependant metabolite trimethylamine N-oxide is associated with hypertension. However, there is a scarcity of literature addressing the role of trimethylamine N-oxide in hypertension pathogenesis. In this review, we discuss the impact of the gut microbiota and gut microbiota dependant trimethylamine N-oxide in the pathogenesis of hypertension. We present evidence from both human and animal studies and further discuss new insights relating to potential therapies for managing hypertension by altering the gut microbiota.

Keywords: TMAO; gut; hypertension; mechanisms; microbiota; trimethylamine N-oxide.

FIGURE 1

Mechanism of TMAO activation of PERK pathway leading to hypertension. TMAO activates the PERK pathway leading to apoptosis, inflammation, and vascular injury resulting in hypertension. TMAO, trimethylamine N-oxide; IRE1α, inositol-requiring protein 1α; ATF6α3, activating transcription factor 6α3; eIF2α, eukaryotic translation initiation factor 2 subunit-α; NADPH, nicotinamide adenine dinucleotide phosphate oxidase; ROS, reactive oxygen species; Ang II, angiotensin II.

FIGURE 2

Proposed model for TMAO-induced hypertension in high salt diet. TMA, trimethylamine; DC, dendritic cell, TMAO, trimethylamine N-oxide; FMO3, flavin-containing monooxygenase-3; IsoLG, Isolevuglandin; AA, arachidonic acid; MHC, major histocompatibility complex; ROS, reactive oxygen species; T_H17 cell, T-helper 17 cell; IL1B, Interleukin-1 beta; IL17A, Interleukin-17A.