Serotonin {60000050}

Shared Reference Notes

• [1.1] 
  - #Bifidobacterium infantis > elevate tryptophan levels in blood plasma > influence central serotonin transmission
• - Candida, Streptococcus, Escherichia, and Enterococcus spp. can produce serotonin
• [1.2] [#Crohn’s disease, #Inflamatory bowel disease] 
  - The blood–brain barrier allows the access of #Tryptophan. - In IBD, especially in CD patients, TRP metabolism increases; consequently, the amino acid levels are reduced with respect to normal healthy individuals, and these changes correlate with the gravity of the disease. - TRP undergoes two major metabolic host pathways, the #kynurenine (KYN) and serotonin (5-HT) biosynthetic pathways, and one microbial pathway to produce #Indole and its derivatives.
• [1.3] 
  - Candida albicans, Escherichia, Streptococci, and Enterococci spp. produce serotonin (5-HT)
• [1.4] [#Parkinson’s Disease] 
  - Serotonin > protective factor of PD
• [1.5] 
  - 5-Hydroxytryptamine (serotonini) > could exert pro- or anti-inflammatory effects in the gut depending on the respective engagement of 5-HT7 versus 5-HT4 receptors.
• [1.6] [#Short Chain Fatty Acid] 
  - SCFAs > directly affect the sympathetic system > thereby increasing the release of mucosal serotonin and affecting learning and memory functions
• [1.7] [#Alzheimer’s disease] 
• [1.8] [#Antibiotic Therapy] 
  - Gut Dysbiosis > increase hypothalamic microRNA-204 (miR-204), a microRNA > reduce SIRT1 and BDNF > decrease in the sympathetic nerve activity > increase the browning of WAT > #Obesity
• [1.9] [#Colorectal cancer] 
  - #Tryptophan > serotonin > can exhibit both a protective and detrimental role. For example, activation of serotonin receptors, 5-HTR1B and 5-HTR2B stimulate tumor angiogenesis and cell proliferation. SCFAs can induce the production and release of serotonin though. In normal conditions, serotonin seems to have mainly a protective role but dysregulation of its production is linked to cancer promotion.
• - 5-HT in the body is synthesized from the essential amino acid #Tryptophan (Trp) in both the brain and gut, and the majority of it (approximately 95% of total 5-HT) resides in the digestive tract and is mostly produced and stored in enterochromaffin cells (ECs). - In the gut, 5-HT is responsible for one of the core signaling pathways, especially in modulating intestinal permeability and regulating mucosal inflammation. - 5-HT is related to colon inflammation in a DSS-induced murine colitis model, and treatment by inhibiting 5-HT production in colonic mucosa has a therapeutic outcome in ameliorating colitis-associated symptoms and inflammation
• [1.11] 
  - bacterial SCFA-#Butyrate regulates the biosynthesis of serotonin, which is responsible for initiating peristalsis.
• [1.12] [#Short Chain Fatty Acid] 
  - SCFAs, serotonin, #kynurenine, #Indole and its derivatives, and #Tryptamine, can bridge the gut and nervous system.
• [1.13] 
  - lack of gut microbiota causes changes in the expression of serotonin 5-HT1 receptors;
• [1.14] [#Celiac Disease, #Migraine] [#CGRP, #Glutamate] 
• [1.15] 
  - #Pu-erh tea could boost the #Indole and 5-hydroxytryptamine pathways of the Trp metabolism.
• - #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)
• [1.16] 
  - A higher relative abundance of #Alistipes species has been reported in children with #Autism, pervasive developmental disorder not otherwise specified (PDD-NOS) , and depression. - #Alistipes may disrupt the gut–brain axis by decreasing serotonin (indole-positive organism) and impair cognition by producing #Propionic acid in rats.
• [1.17] [#Parkinson’s Disease] 
  - #Tryptophan, an essential amino acid only derived from microbiome or diet, is the rate limiting precursor to serotonin. #Tryptophan biosynthesis pathway was reduced in PD. - spore forming bacteria modulate serotonin production and enhance gut motility - #Constipation, a common symptom of PD, may be related to the depletion of spore forming bacteria.
• [1.18] 
  - #Tryptophan metabolites are produced via four different pathways: The serotonin pathway, the #Tryptamine pathway, the #kynurenine pathway, and the bacterial #Indole pathway.
• [1.19] 
  - #Eggerthella is involved in the synthesis of serotonin and gamma aminobutyric acid (#GABA).
• - serotonin produced by the gut cannot cross the blood-brain barrier, it can affect the blood-brain barrier permeability, which can lead to inflammation of the brain.
• [#Bipolar disorder, #Major depressive disorder, #Schizophrenia] [#Quinolinic acid, #kynurenine] - shift in the #Tryptophan metabolism from serotonin to the kyn pathway is associated with BD, MDD and SZ, but only in mood disorders (BD and MDD) there was a preferential metabolism of Kyn to the potentially neurotoxic QA.
• [#Bipolar disorder] - in BD > Especially, #GABA, #Glutamate, serotonin, #Dopamine, norepinephrine and #Acetylcholine appears to be importantly dysregulated in these patients
• - serotonin can affect both vagus nerve and BBB permeability, and it modulates intestinal inflammation.
• - #Tryptophan can cross the BBB, serotonin produced in the gut cannot.
• [1.21] 
  - 95 % of all serotonin synthesis occurs in the GIT, which influences its availability in the brain.
• [1.22] [#Anorexia nervosa, #Bulimia nervosa] [#Bacteroides uniformis] 
  - Individuals with AN lacking the genomic region of B. uniformis had greater scores for self-denial and bulimia. - The genetic deletion in B. uniformis could result in the deficiency of thiamine, a vitamin associated with intestinal and mental health. - The serotonin synthesis module causally affected BMI through #Glycoursodeoxycholic acid, which is upregulated by serotonin.
• [#Anorexia nervosa] - The abundance of GBMs for serotonin synthesis and degradation of #Tryptophan, #Glutamate, and #Dopamine, were enriched in AN.
• [1.23] [#α-tocopherol] 
  - microbial metabolites such as α-tocopherol, #Tyramine, #p-aminobenzoate, and #Indole impact serotonin 5-HT secretion by enteroendocrine cells in the intestine.
• [1.24] [#Depression] 
  - inoculation of healthy mice with GM from UCMS mice activates the Vagus Nerve and induces early and sustained changes in both serotonin and #Dopamine neurotransmission pathways in the brainstem and HPC. - #Vagotomy abrogates adult HPC neurogenesis deficits, neuroinflammation and depressive-like behavior, suggesting that vagal afferent pathways are necessary to drive GM-mediated effects on the brain.
• [1.25] 
  - #Tyramine, #Deoxycholic acid, and #4-aminobenzoic acid have been reported to stimulate serotonin synthesis
• - norepinephrine, indole, #Indole-3-aldehyde, #Isovaleric acid, #Butyric acid, and #Isobutyric acid stimulate serotonin release from enterochromaffin cells.
• [#Short Chain Fatty Acid] - gut microbiota may promote the development of functional #Constipation through microbial metabolites, including #Bile Acids, SCFAs, 5-hydroxytryptamine, and #Methane.
• [1.26] 
  - #Tryptophan is mostly shunted into the #kynurenine pathway but is also the primary metabolite for serotonin production and the bacterial #Indole pathway.
• [#Tryptophan] - Digestion of Trp results in the well-known neuroactive compounds, serotonin and #Melatonin, and is a starting point for the NAD+ -producing #kynurenine pathway in human
• [1.27] 
  - Serotonin levels could predict an increased risk for osteoporotic fractures, gut-derived serotonin reduces osteoblast proliferation and inhibits bone formation leading to a decrease in BMD and a higher risk of #Osteoporosis
• [1.28] [#Autism] 
  - FMT in the ASD cohort could decrease #GABA and serotonin in serum, but the #Dopamine level was increased by FMT.
• [#Autism] - FMT could exhibit a recovery effect on the serum levels of serotonin, #GABA, and DA in the ASD cohort, which means that FMT might be an effective technique in regulating #Neurotransmitters via the MGB axis
• [#Blood Brain Barrier Integrity] - #Tryptophan can cross the BBB and affect serotonin synthesis in CNS
• - #Streptococcus and #Enterococcus produce serotonin
• - #Lactococcus lactis subsp. cremoris, L. lactis subsp. lactis, #Lactobacillus plantarum, #Streptococcus thermophilus, #Escherichia coli, #Morganella morganii, #Klebsiella pneumoniae, and #Hafnia alvei produce serotonin
• - #Escherichia produces #Norepinephrine, serotonin, and #Dopamine
• [1.29] [#Acetylcholine, #Noradrenalin] [#Keto diet] 
  - concentrations of 5-HT, NE, AC, and cAMP of SHR in the KD group were strikingly higher than that in the ND group.
• [#Alzheimer’s disease] - #Tryptophan depletion increases cognitive deficits among people with AD and the bioavailability of metabolites in the serotonin and #kynurenine pathways are altered in both the urine and serum of AD patients
• [1.31] 
  - increasing serotonin synthesis from intestinal endocrine cells has been linked to #Depression and #Autism.
• - There is currently no evidence that bacterial serotonin production contributes to the pathogenesis of #Irritable bowel syndrome (IBS)
• - #Tryptamine stimulates the release of serotonin from intestinal endocrine cells.
• [1.32] [#Depression] [#Exercise training] 
  - Voluntary exercise-induced antidepressant properties might be partially caused by suppression of serotonin uptake into gut microbiota and increase the permeability of the blood-brain barrier via reduced #Propionate production.
• [1.33] 
  - low levels of cerebral serotonin were strongly associated with #Migraine. - migraineurs have higher levels of cerebral serotonin during an acute pain attack compared with the periods between attacks
• [1.34] [#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
• [1.35] 
  - #Indole is an inter-kingdom signal in gut epithelial cells, reinforcing the host cell-barrier assets - It is derived from #Tryptophan, produced by several microbes (i.e., #Bacteroides, #Clostridium, #Desulfovibrio) colonizing the human GI tract - It is a critical precursor of physiologically important molecules, such as serotonin and #Melatonin
• - GM #Indole derivatives may influence the level of serotonin precursors that affect the amount of serotonin in the brain.
• [1.36] [#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.
• [1.37] [#Tryptophan] 
  - #Fructooligosaccharides have been shown to modulate the gut microbial composition, by decreasing the abundance of #Akkermansiaceae (family level) and #Verrucomicrobia (phylum level) and increasing the abundance of #Ruminococcaceae (phylum level), and to increase the levels of Trp and 5-HT in mice models
• [#Irritable bowel syndrome] - serotonin levels are increased in both patients with #Diarrhea predominant and #Constipation predominant IBS. - increased levels of 5-HT in patients with #Diarrhea predominant IBS in both fasting and fed conditions, whereas patients with #Constipation predominant IBS did not show increased levels of 5-HT after meal ingestion.
• [#Tryptophan] - #Lactococcus lactis subsp. cremoris (MG 1363), L. lactis subsp. lactis (IL1403), #Lactobacillus plantarum (FI8595), #Streptococcus thermophilus (NCFB2392), #Escherichia coli K-12, #Morganella morganii (NCIMB, 10466), #Klebsiella pneumoniae (NCIMB, 673), and #Hafnia alvei (NCIMB, 11999) that can produce serotonin from Trp
• [#Irritable bowel syndrome] - increased plasma 5-HT levels in patients with IBS and the presence of #Bifidobacteriaceae, #Bacteroidaceae, #Oscillospiraceae, and the bacteriophages #Podoviridae in the gut microbiota.
• [#Irritable bowel syndrome] - 5-HT levels are lower in Plasma of IBS patients compared to the healthy controls and it is associated with a low expression of the re-uptake transporters for TPH1 and serotoni
• - Serotonin is known to contribute to feelings of satiety and fullness. - Low serotonin levels have been associated with an increased appetite and cravings for carbohydrate-rich foods.
• - The gut microbiota is apparently responsible for the maturation of the #Adult ENS through the release of 5-HT and activation of 5-HT4 receptors, indicating its involvement in the normal peristaltic function of the gut
• [1.38] [#Neonate] 
  - in neonates > 5-HT directly alters T cell metabolism to promote the differentiation of Tregs and thereby long-term immune tolerance toward both dietary antigens and commensal bacteria.
• [1.39] [#Alzheimer’s disease] 
  - microbial-derived #Tryptophan degradation as one of the primary microbial sources of #Formate. - #Tryptophan depletion increases cognitive deficits among people with AD and the bioavailability of metabolites in the serotonin and #kynurenine pathways are altered in both the urine and serum of AD patients
• - #Turicibacter sanguinis plays roles in serotonin utilization and pathways of steroid and lipid metabolism.
• [1.41] 
  - #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.

References Notes