Comment: It has been known since the 1940s that not only is 5-HT produced predominantly in theGI tract, but also that elevated serotonin levels are causally linked to aplethora of chronic conditions, especially various inflammatory bowel diseases(IBD) such as Crohn’s, ulcerative colitis (UC), irritable bowel syndrome (IBS),and even cancer (carcinoid tumors)…the study above demonstrates that 5-HT is a major causal factor in IBD, and perhaps a host of other issues seemingly unrelated to the GI tract. Worse, the study cites direct evidence that the very usage of those SSRI drugs is likely a causal factor in all of these disease. Those other conditions include Parkinson disease (PD), AlzheimerDisease (AD), Multiple sclerosis (MS), theumatoid arthritis (RA), Lupus, diabetes, osteoporosis, hypogonadism, mental illness, cancer, etc since all of them have been found to be at least partially caused by impaired autophagy, and the study below demonstrates that a major mechanism of 5-HT’s pathological role is by impairing autophagy. Now, since 5-HT production in the GI tract largely depends on the production of endotoxin, the study once again implicates endotoxin/LPS and ultimately the microbiome, as the top-level cause ofvirtually all chronic diseases. Link: http://haidut.me/?p=1677

Enterochromaffin (EC) cells, a subset of enteroendocrine cells, produce approximately 90% of serotonin [5-hydroxytryptamine (5-HT)] in the gut (18, 19). In EC cells, the synthesis of 5-HT begins with the conversion of dietary tryptophan to 5-hydroxy-L-tryptophan (5-HTP), a process catalyzed by the rate-limiting enzyme, tryptophan hydroxylase (Tph) (18). There are two isoforms of the Tph enzyme, Tph1, present mainly in EC cells, and Tph2, found in the brain stem and enteric neurons (18, 20). 5-HTP is converted into 5-HT by aromatic L-amino acid decarboxylase. Apical and basolateral release of 5-HT from EC cells occurs in response to mechanical and various chemical stimulants (20). Once released, 5-HT is taken up by surrounding IECs and immune cells by the serotonin reuptake transporter (SERT) (20).