MetaBiom
Microbiome & Chronic Diseases

Evidence Based Medicine

TMAO {60000064}

Record Keys


Biotic:
TMAO
Class:[  ]
Queue:[  ]

Details


Initialisation date:
2020-09-23
Specification:

trimethylamine-N-oxide

Source:
[  ]

Links


Meta Information


Structural Type:[  ]
Functional Type:[  ]
Function:
Pro-inflammatory, Building cholesterol plaques

Notes


- trimethylamine N-oxide (TMAO) is risk indicator for cardiovascular diseases, diabetes mellitus, nonalcoholic fatty liver disease, and other metabolic events. As the end-product of dietary choline and L-carnitine, TMAO is converted from trimethylamine (TMA) in the liver by flavin-containing monooxygenases (FMOs), especially FMO3.
- TMAO promotes the release of the inflammatory cytokines IL-1β and IL-18 via activation of the NLRP3 inflammasome from foetal human colon cells in a time- and dose-dependent manner
TMAO induces inflammation by activating the ROS-TXNIP-NLRP3 inflammasome, thereby contributing to endothelial dysfunction in human umbilical vein endothelial cells
- injection of TMAO was shown to significantly increase inflammatory markers, including cyclooxygenase 2, IL-6, E-selectin, and ICAM1, through the MAPK and NF-κB signalling pathways, which then recruit leukocytes and induce vascular inflammation.

- TMAO aggravates triglyceride accumulation and lipogenesis in the livers of high-fat diet-fed mice.

-TMAO promotes vascular endothelial cell pyroptosis via ROS production, thus resulting in the development of atherosclerosis

Shared Notes


  • [1.2
    - Gut microbe-dependent metabolite, produced from degradation of choline and L-carnitine
  • [1.3
    - TMAO is asociated with platelet hyperactivity, lipid disorders, and oxidative stress
  • [1.4
    - Regardless of the initial TMAO levels, 10-year increases in TMAO from the first to second blood collection were significantly associated with an increased risk of CHD
  • [1.5
    - Patients with MCI and AD also show higher levels of gut microbiota-derived trimethylamine N-oxide (TMAO) in the cerebrospinal fluid.
    - TMAO correlate with AD biomarkers including pTau, total Tau, and Aβ42.
    - TMAO treatment reduces cognitive function and aging signs in mice, by ameliorating neuronal senescence and mitochondrial dysfunction.
    - TMAO and its precursors have inflammatory biomarkers, possibly contributing to AD-related leaky gut.
  • - The Western diet consists of low-fiber, high-fat, and high-protein foods, where it is common to eat fatty red meats and eggs that are rich in TMA and choline, thus increase TMAO production.
  • [1.1
    - TMA and subsequent conversion to TMAO by host FMO3 is related to T2DM pathogenesis and comorbidities.
    - Mice with selective hepatic insulin resistance have elevated levels of circulating TMAO.
    - Dietary supplementation with TMAO can exacerbate glucose intolerance in high-fat–fed mice.
    - High concentrations TMAO directly binds to and activates PERK, a key effector of the unfolded protein response in the liver, promoting hyperglycemia and metabolic dysfunction
  • - TMAO was found to contribute to thrombotic events by causing platelet hyperactivity

Common References