Understanding the role of tryptophan and serotonin metabolism in gastrointestinal function

Keszthelyi, Dániel; Troost, Freddy J.; Masclee, Ad

doi:10.1111/j.1365-2982.2009.01370.x

Cited by 285 publications

(260 citation statements)

References 60 publications

(112 reference statements)

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“…Produced from tryptophan it plays a key role in multiple processes and only a small percentage of 5-HT is found in the brain with over 90% found in the GI tract (Keszthelyi et al, 2009). In the gut it is mainly stored in the enterochromaffin cells of the intestinal mucosa and the remainder in the serotonergic neurons of the enteric nervous system (Keszthelyi et al, 2009). Most antidepressants currently marketed impact 5-HT (Cryan and O'Leary, 2010).…”

Section: Microbiota and Humoral Responsesmentioning

confidence: 99%

Microbes, Immunity, and Behavior: Psychoneuroimmunology Meets the Microbiome

Dinan

Cryan

2016

Neuropsychopharmacol

183

110

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There is now a large volume of evidence to support the view that the immune system is a key communication pathway between the gut and brain, which plays an important role in stress-related psychopathologies and thus provides a potentially fruitful target for psychotropic intervention. The gut microbiota is a complex ecosystem with a diverse range of organisms and a sophisticated genomic structure. Bacteria within the gut are estimated to weigh in excess of 1 kg in the adult human and the microbes within not only produce antimicrobial peptides, short chain fatty acids, and vitamins, but also most of the common neurotransmitters found in the human brain. That the microbial content of the gut plays a key role in immune development is now beyond doubt. Early disruption of the host-microbe interplay can have lifelong consequences, not just in terms of intestinal function but in distal organs including the brain. It is clear that the immune system and nervous system are in continuous communication in order to maintain a state of homeostasis. Significant gaps in knowledge remain about the effect of the gut microbiota in coordinating the immune-nervous systems dialogue. However, studies using germ-free animals, infective models, prebiotics, probiotics, and antibiotics have increased our understanding of the interplay. Early life stress can have a lifelong impact on the microbial content of the intestine and permanently alter immune functioning. That early life stress can also impact adult psychopathology has long been appreciated in psychiatry. The challenge now is to fully decipher the molecular mechanisms that link the gut microbiota, immune, and central nervous systems in a network of communication that impacts behavior patterns and psychopathology, to eventually translate these findings to the human situation both in health and disease. Even at this juncture, there is evidence to pinpoint key sites of communication where gut microbial interventions either with drugs or diet or perhaps fecal microbiota transplantation may positively impact mental health.

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Section: Microbiota and Humoral Responsesmentioning

confidence: 99%

Microbes, Immunity, and Behavior: Psychoneuroimmunology Meets the Microbiome

Dinan

Cryan

2016

Neuropsychopharmacol

183

110

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“…Most catabolites are biologically active and involved in the pathogenesis of many disease processes [7][8][9][10][11][12]. Furthermore, the interrelationship between metabolic pathways is of profound pharmacological and physiological importance as changes in one pathway might have secondary effects on the others [1]. New physiological roles and correlations between the different pathways can only be described by the simultaneous detection of all the metabolites.…”

Section: Introductionmentioning

confidence: 99%

“…As shown in Fig. 1, Trp catabolism proceeds mainly via three pathways in mammalians [1]: the kynurenine and serotonin Electronic supplementary material The online version of this article (doi:10.1007/s00216-011-5436-y) contains supplementary material, which is available to authorized users. pathways as well as bacterial degradation.…”

Section: Introductionmentioning

confidence: 99%

Quantitative profiling of tryptophan metabolites in serum, urine, and cell culture supernatants by liquid chromatography–tandem mass spectrometry

et al. 2011

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A sensitive, selective, and comprehensive method for the quantitative determination of tryptophan and 18 of its key metabolites in serum, urine, and cell culture supernatants was developed. The analytes were separated on a C18 silica column by reversed-phase liquid chromatography and detected by electrospray ionization tandem mass spectrometry in positive ion multiple reaction monitoring (MRM) mode, except for indoxyl sulfate which was measured in negative ion MRM mode in a separate run. The limits of detection and lower limits of quantification were in the range of 0.1-50 and 0.5-100 nM, respectively. Fully 13 C isotope-labeled and deuterated internal standards were used to achieve accurate quantification. The applicability of the method to analyze serum, urine, and cell culture supernatants was demonstrated by recovery experiments and the evaluation of matrix effects. Precision for the analysis of serum, urine, and cell culture supernatants ranged between 1.3% and 16.0%, 1.5% and 13.5%, and 1.0% and 17.4%, respectively. The method was applied to analyze changes in tryptophan metabolism in cell culture supernatants from IFN-γ-treated monocytes and immature or mature dendritic cells.

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“…Over 95% of 5-HT is produced in the digestive tract (13). Accordingly, urinary excretion of 5-HT and its metabolite, 5-HIAA, reflects systemic l-Trp metabolism via the 5-HT pathway.…”

Section: Resultsmentioning

confidence: 99%