TMA {60000037}

Shared Reference Notes

• [1.1] 
  - Common commensal bacteria produce the volatile trimethylamine (TMA) by cleaving it from choline, carnitine, betaine, and phosphatidylcholine. - After reaching portal circulation and trafficking to the liver TMA is oxidized to trimethylamine-N-oxide (TMAO) by flavin-containing monooxygenases (FMOs), most predominantly FMO3
• [1.2] [#Atherosclerosis, #Coronary artery disease] 
  - #Bilophila, a genus of gut microbes, can metabolize TMA, resulting in lower #TMAO, suggesting that differences in TMA-metabolizing gut bacteria in individuals lead to different ultimate effects, and replacement of relevant bacteria may reduce the risk from #TMAO.
• [#Para-cresol] - #TMAO is the hepatic oxidation product of the microbial trimethylamine (TMA). - dietary supplementation with #TMAO was shown to promote atherogenesis and development of #Atherosclerosis in mice. - #TMAO levels associate with an increased risk of adverse cardiovascular events. - Carotid #Atherosclerosis was demonstrated to be associated with gut microbial metabolites (especially #TMAO and p-cresol sulfate) in >3,000 patients, which could serve as an independent predictor of the disease.
• [1.3] [#Metabolic Dysfunction-associated Steatohepatitis, #Metabolic associated fatty liver disease] [#Lipopolysaccharide] 
  - A shift in the metabolic function of intestinal bacteria is predominantly caused by dysbiosis. In the intestine, it leads to an increase in the permeability of intestinal mucosa for LPS and ultimately causes chronic inflammation. Concentration of bacterial metabolites in the blood, such as trimethylamine which is metabolized in the liver to trimethylamine-N-oxide (#TMAO) correlates with the severity of #Steatohepatitis
• [1.4] 
  - In a mouse model, it was demonstrated that #Methanobrevibacter smithii, #Methanosarcina mazei, and #Methanomicrococcus blatticola use TMA as growth substrates, resulting in reduced #Atherosclerosis
• [1.5] [#Atherosclerosis] 
  - Trimethylamine (TMA) is generated by the gut microbiome and in the host converted by flavin-containing monooxygenase (FMO3) into trimethylamine N-oxide (#TMAO), which has been implicated in chronic cardiovascular and metabolic diseases. - Using cell culture systems and patient biopsies > #TMAO reprograms skin fibroblasts, vascular endothelial cells, and adipocytic progenitor cells into myofibroblasts via the putative #TMAO receptor protein R-like endoplasmic reticulum kinase (PERK). - FMO3 was detected in skin fibroblasts and its expression stimulated by TGF-β1. - FMO3 was elevated in #Systemic sclerosis skin biopsies and in #Systemic sclerosis fibroblasts.
• [1.6] 
  - Animal products such as meat, fish, and eggs are rich in TMA precursors.
• [1.7] [#Egg Consumption, #Meat-based diet] 
  - dietary #Choline or L-#Carnitine, which are found in foods such as meat and eggs, are metabolized by the gut microbiota into TMA in the intestine. - TMA enters the blood circulation and is transformed into #TMAO in the liver.
• - gut microbe–derived metabolite trimethylamine N-oxide (#TMAO), enhanced antitumor immunity to Pancreatic ductal adenocarcinoma (PDAC) - Delivery of #TMAO intraperitoneally or via a dietary choline supplement to orthotopic PDAC-bearing mice reduced tumor growth, associated with an immunostimulatory tumor-associated macrophage (TAM) phenotype, and activated effector T cell response in the tumor microenvironment. - #TMAO potentiated the type I interferon (IFN) pathway and conferred antitumor effects in a type I IFN–dependent manner. - bacteria producing an enzyme that generates TMA was associated with positive immunotherapy outcomes in people with #Pancreatic Cancer. - #Bacillus and #Paenibacillus species, were present at higher levels in people who survived for a long period of time after #Pancreatic Cancer.
• [1.8] [#Parkinson’s Disease] 
  - Circulating levels of #TMAO, a gut microbiome derived oxidation product of TMA, are reportedly elevated in PD and correlate with disease progression and severity. Gene families involved in TMA production were elevated in PD, including cutC (choline lyase) which cleaves choline to produce TMA , and caiT (L-carnitine/gamma-butyrobetaine antiporter) which exchanges carnitine for gamma-butyrobetaine before TMA can be produced.
• [1.9] [#Human gammaherpesvirus 4] 
  - #Tomato > Fruitflow when administered over 4 wk at 2×150 mg Fruitflow per d > Significant changes in relative abundance of microbial taxa with Fruitflow, such as decreases in #Bacteroides, Ruminococccus, and #Hungatella related OTUs, as well as increases in #Alistipes which are all known for the involvement in TMA/#TMAO metabolism.
• [#Meat-based diet] - The animal meat-derived metabolites #Carnitine, #Choline, or #Phosphocholine (PC) are degraded by gut bacteria to trimethylamine (TMA), which is further metabolized in the liver to trimethylamine N-oxide (#TMAO)
• - The microbiota metabolizes phosphatidylcholine, #Choline, and #Carnitine to produce trimethylamine (TMA), which is further metabolized in the liver to trimethylamine-N-oxide (#TMAO).
• [1.11] 
  - #Hungatella is associated with #Paleolithic diet and is known to produce the precursor molecule for trimethylamine-N-oxide (#TMAO).
• [1.12] [#Atherosclerosis, #CVD] [#Lipopolysaccharide, #TMAO] 
• [1.13] 
  - members of the seventh order of methanogens may decrease the concentration of TMA by converting it to #Methane, resulting in #Archaea-mediated TMA depletion before it reaches the liver.
• [#Clostridium clusters XIVa] - Components with the[N(CH3)3] structure, such as #Choline, #Phosphatidylcholine, and L-#Carnitine, can be used by #Clostridium (primarily #Clostridium XIVa and #Eubacterium) and Proteobacterium produced trimethylamine (TMA) lyases to form TMA. - TMA is a foul-smelling gas that smells like rotten fish
• [1.14] 
  - #Lachnoclostridium could affect cardiometabolic health by lowering #Acetate levels and producing harmful lipid compounds, including trimethylamine and CDP-diacylglycerol
• [1.15] [#Clostridium asparagiforme, #Clostridium citroniae, #Clostridium hathewayi, #Clostridium sporogenes] [#TMAO] 
  - #Clostridium sp (C asparagiforme, C citroniae, C hathewayi, and C sporogenes), #Desulfovibrio, and #Enterobacteriaceae (#Escherichia coli and #Acinetobacter sp), can respond to a diet rich in #Choline, an essential nutrient for omnivores, and convert it to trimethylamine, which is then metabolised in the liver to trimethylamine N-oxide, a microbiome derived proatherogenic metabolite.
• [1.16] [#Meat-based diet] 
  - TMA is synthesized from #Choline found in eggs, red meat or fish and is subsequently transformed in the liver into its active metabolite trimethylamine Noxide (#TMAO), which eventually acts as a neuronal protein stabilizer.
• - TMA is the main agonist interacting with trace amine–associated receptors (TAARs), a family of G-protein–coupled receptors that are further classified into 9 different subfamilies expressed in the human brain and other peripheral organs. - The most highly expressed receptor subtype, namely TAAR5, has been detected in several human brain areas, including the amygdala, hippocampus, caudate nucleus, thalamus, hypothalamus and substantia nigra. - TAAR5-knockout mice displayed altered emotional behaviour, particularly anxiety- and #Depression-like behaviour, as well as impaired brain #Serotonin (5-HT) neurotransmission.
• - Distinct VOC signatures for #Schizophrenia were m/z 60 and m/z 74. The first of these was identified as trimethylamine (TMA). - patients with #Schizophrenia displayed a significantly lower concentration of TMA in their breath. - Decreased production of TMA is found in patients with #Choline-deficient diets, in nonalcoholic #Steatohepatitis and may result in #Obesity and #Hyperglycemia, which are often seen in patients with #Schizophrenia.
• [1.17] [#Quinolinic acid] [#High Fat Diet] 
  - QA inhibits the increase of #Cholesterol, TMA, #TMAO, CXCL13, TIMP-1 and HMGB1 levels in peripheral blood of Apoe−/− mice induced by HFD, suggesting that QA can effectively inhibit HFD-induced #Atherosclerosis.
• [1.18] [#Lithocholic acid] 
  - #Lachnoclostridium is described with higher microbial capacity for bile acid conversion through a 7α-dehydratase process38, explained the robust increase in LCA abundance. - #Lachnoclostridium produces trimethylamine (TMA), which was turned into trimethylamine-N-oxide (#TMAO) in liver

References Notes