Tryptamine {60000056}

Shared Reference Notes

• [1.1] 
  - Tryptamine is found abundantly in human and rodent stool samples. - The role of tryptamine in the GI tract is facilitated by the 5-HT4 receptor that is only found in colonic epithelium. - Tryptamine produced increase movement across the colonic epithelium as well as fluid secretions in colonoids for proper intestinal secretion. - Improved GI motility was seen in GF mice that were colonized with tryptamine-producing engineered Bacteroides thetaiotaomicron microbes.
• [1.2] 
  - #Clostridium sporogenes is able to decarboxylate Trp leading to the production of the neurotransmitter tryptamine.
• [1.3] [#Indole-3-acetic acid, #Indole-3-propionic acid, #Tryptophan] 
  - TRP > utilized by the intestinal flora in the intestinal tract and metabolized into ligand molecules indole, indole propionic acid, indole acetic acid, #Skatole, and tryptamine > action on of aryl hydrocarbon receptor (AHR).
• [1.4] 
  - #Clostridium perfringens also metabolizes tryptophan to tryptamine, a metabolite that decreases macrophage inflammatory indicators and reduces pro-inflammatory cytokines stimulated by fatty acids and LPS.
• [#Short Chain Fatty Acid] - SCFAs, #Serotonin, #kynurenine, #Indole and its derivatives, and tryptamine, can bridge the gut and nervous system.
• [1.5] [#Indole-3-acetamide (IAM), #Indole-3-acetic acid, #Indole-3-aldehyde, #Indole-3-lactic acid, #Indole-3-propionic acid, #Indole-3-pyruvic acid (IPyA), #Indoleacrylic acid (IA)] 
  - For AhR, the most effective Trp metabolites are #Indole, #Skatole, IA, tryptamine, IPyA and #Indole-3-acetamide (IAM), whereas IAA, IAID, IPA and ILA are the least active
• - Tryptamine induces the release of the neurotransmitter 5-HT, a #Serotonin of enterochromaffin cells. - 5-HT can work on the enteric nervous system to stimulate gastrointestinal motility such as #Irritable bowel syndrome (IBS)
• [1.6] 
  - #Tryptophan metabolites are produced via four different pathways: The #Serotonin pathway, the tryptamine pathway, the #kynurenine pathway, and the bacterial #Indole pathway.
• [1.7] [#Indole-3-propionic acid] 
  - The GM metabolism of #Tryptophan also leads to the production of six neuroactive compounds altogether called TRYP-6 affecting the Gut-Brain Axis (GBA). - These six metabolites include #Indole-3-acetic acid, quinolinate, #kynurenine, indole, tryptamine and indole propionic acid
• [1.8] [#Aromatic amino acid] 
  - #Ruminococcus gnavus is the main producer of tryptamine in #Infants’ gut.
• [1.9] [#Clostridium sporogenes] [#Tryptophan] 
  - Two gut #Bacteria C. sporogenes and #Ruminococcus gnavus can convert Trp into tryptamine which is able to inhibit #Glucose-induced #Hyperglycemia and enhance insulin release.
• [#Clostridium boltae] - #Blautia hansenii, Enterocloster (Clostridium) boltae and #Enterococcus faecalis and have also been shown to produce tryptamine and #Phenethylamine by recent studies
• [#Diabetes Type 2, #Irritable bowel syndrome] [#Ruminococcus gnavus] [#High fibre diet] - fiber intervention significantly suppressed tryptamine and #Phenethylamine levels and abundances of R. gnavus in T2D subjects, revealing manipulation of gut microbiota-derived tryptamine and #Phenethylamine by dietary changes or prebiotics is a potential direction for managing #Metabolic syndrome and IBS.
• [#Diabetes Type 2, #Irritable bowel syndrome] [#Ruminococcus gnavus] - tryptamine and phenethylamine derived from the R. gnavus-mediated catabolism on dietary amino acids impaired insulin sensitivity via activation of TAAR1-MAPK/ERK signaling pathway axis, thereby contributing to insulin resistance in gut dysbiosis-associated IBS and T2D.
• [#Diabetes Type 2] [#Blautia hansenii] - increased abundances of other tryptamine and #Phenethylamine producer B. hansenii in #Metabolic syndrome
• [#Diabetes Type 2] - tryptamine and #Phenethylamine can stimulate insulin secretion but both acute and long-term exposure to TAAR1 activators tryptamine and #Phenethylamine impair insulin sensitivity
• [#Diabetes Type 2] [#Ruminococcus gnavus] - tryptamine/#Phenethylamine-mediated TAAR1 signaling pathway as the key molecular axis underlying R. gnavus-induced insulin resistance
• - TAAR1 is an amine-activated G protein-coupled receptor that is activated by gut microbes-derived aromatic trace amines including tryptamine, #Phenethylamine, and #Tyramine in gut
• [#Ruminococcus gnavus] - tryptamine and #Phenethylamine as TAAR1 ligands are the culprits and one possible way to design a therapeutic approach is to facilitate the reduction of R. gnavus or on top of blocking the tryptamine and #Phenethylamine production by inhibiting the bacterial TDC
• [#Ruminococcus gnavus] - R. gnavus reduction accompanied by downregulation of tryptamine and #Phenethylamine are positively correlated with the improvement of insulin resistance.
• [#Ruminococcus gnavus] - Among these tryptamine and #Phenethylamine-producing bacteria species, R. gnavus has the highest catalytic ability to transform aromatic amino acids into aromatic trace amines (tryptamine, #Tyramine, and #Phenethylamine) compared with other bacteria specie
• [1.11] 
  - enterobacterial metabolite #Norharman, which was partly exogenous and generated from #Tryptophan metabolism regulated by #Lactobacillus, showed the strongest inhibitory effect on M1 macrophage activation. - As a neuroactive β-carboline, #Norharman is a pyridoindole alkaloid that is naturally occurring, is plant-derived or in thermally processed foods, and is formed by the condensation of indoleamine (such as tryptamine) and formaldehyde, showing antioxidant, anti-inflammatory, and antitumor activities
• [1.12] [#Allergy] 
  - Several maturation-dependent metabolites were disturbed in #Children who developed allergies with three biogenic amines, namely #Phenylethylamine, tryptamine, and #Tyramine, also demonstrating high correlations with disrupted microbial pathways. - This Trace amines (TAs) have a very high affinity for TA-associated receptors (TAARs), a class of G-coupled protein receptors found on both intestinal and immune cells, and TAAR ligation has been demonstrated to increase intestinal cell oxidative stress and immune cell activation. - their accumulation promotes bacterial adherence to intestinal cells, likely perpetuating this inflammatory response
• [1.13] [#Indole-3-acetic acid] 
  - #Lactobacillus can use #Tryptophan instead of #Glucose as a source of energy, and produce #AHR ligands such as #Indole-3-acetic acid (IAA), tryptamine (TA) and 3-methyl #Indole
• [1.14] 
  - Tryptamine functions as a neurotransmitter that regulates intestinal motility and immune function by acting as a ligand for the aryl hydrocarbon receptor (#AHR)
• [#Indole-3-lactic acid, #Indole-3-propionic acid] - #Clostridium sporogenes, for example, converts #Tryptophan into tryptamine, indoleacetic acid (ILA), and #Indole #Propionic acid (IPA)
• - tryptamine stimulates the release of #Serotonin from intestinal endocrine cells.
• [1.15] [#Multiple Sclerosis] 
  - Tryptamine is a neuromodulator with antioxidant characteristics that is produced when commensal bacteria break down #Tryptophan. - Deficits in #Tryptophan-derived #Neurotransmitters like #Serotonin and #Melatonin, which are both essential for #Sleep, are frequently linked to MS comorbidities, including #Depression
• [1.16] [#Inflamatory bowel disease] [#Ruminococcus gnavus] 
  - In patients with IBD, R. gnavus has been found to be highly abundant and positively correlated with tryptamine levels.
• [#Ruminococcus gnavus] - R. gnavus is capable of producing tryptamine, which can affect gut motility through several mechanisms. - First, tryptamine activates the #Serotonin receptor 4 (SR4) or #5-hydroxytryptamine receptor 4 (5-HT4R), leading to an increase in intracellular cyclic #Adenosine monophosphate (cAMP) concentration > This elevation in cAMP levels can enhance gut motility. - Second, tryptamine can also increase fluid secretion by acting on the cystic fibrosis transmembrane regulator (CFTR) > promotes the secretion of fluids into the gut, affecting gut motility.
• [1.17] [#Tryptophan] 
  - Trp is converted to #Indole via the enzyme Trp identified in gut bacteria such as #Escherichia coli (E. coli), #Clostridium spp., and #Bacteroides spp. - Trp decarboxylase converts Trp to tryptamine > is expressed in #Clostridium, #Ruminococcus, #Blautia, and #Lactobacillus bacteria

References Notes