Acute tryptophan depletion affects brain-gut responses in irritable bowel syndrome patients and controls

Abstract

Background: Serotonin, a key denominator of the brain-gut axis, is involved in the regulation of gastrointestinal motility, secretion, and perception as well as cognition and mood. Aim: To assess the effects of an acutely lowered serotonin synthesis, using the acute tryptophan depletion (ATD) method, on visceral perception, affective memory performance, and mood in diarrhoea predominant irritable bowel syndrome patients (d-IBS) and controls. Methods: In a randomised, double blind, crossover design, 14 d-IBS patients and fourteen matched controls were studied under ATD and placebo conditions, respectively. Perception of urge and pain was scored during rectal distensions. Affective memory performance, mood, and biochemical parameters of serotonergic metabolism were simultaneously assessed. Results: ATD significantly decreased plasma tryptophan (67.0 (2.0) v 24.9 (2.0) mmol/l) and 5-hydroxyindole acetic acid concentrations (29.9 (1.0) v 15.8 (0.6) nmol/l). ATD was associated with significantly increased urge scores specifically in the lower pressure range and overall increased pain scores. ATD significantly lowered the perceptual threshold for first perception compared with placebo (patients 10.6 (1.2) v 13.6 (0.8) mm Hg, controls 12.6 (1.3) v 15.7 (1.2) mm Hg) but not for maximal tolerable discomfort (patients 50.5 (3.6) v 51.6 (3.3) mm Hg, controls 50.9 (3.3) v 48.8 (2.9) mm Hg). ATD induced a significant shift in affective memory bias towards preferential loss of positive material but no significant changes in mood. ATD did not differentially affect the patient or control group. Conclusions: We have provided evidence that serotonergic modulation by ATD affects both visceral perception as well as cognition in d-IBS and controls. Simultaneous measurement of brain and gut function and the application of ATD contribute to the elucidation of the complex pathophysiology of IBS.

Kynurenine pathway metabolism and the microbiota-gut-brain axis

“…Acute tryptophan depletion (ATD) is the most common clinical method to determine the impact of manipulating peripheral levels of tryptophan on CNS and ENS function, and has been utilised to investigate brain-gut axis communication in healthy control participants and individuals with IBS (Kilkens et al, 2005;Kilkens et al, 2004;Labus et al, 2011;Shufflebotham et al, 2006). Systemic free tryptophan competes with all other large neutral amino acids (LNAAs; valine, leucine, isoleucine, methionine, phenylalanine and tyrosines) for transportation across the BBB (Silber and Schmitt, 2010) where once across, it is subsequently synthesised into a variety of agents including kynurenine via specific metabolic processes.…”

Evidence-based clinical practice guidelines for irritable bowel syndrome

“…The leading neurotransmitter responsible for the pathology of IBS is serotonin. Depletion of tryptophan, a serotonin precursor, causes visceral hypersensitivity [21] and elicits fear [22] in IBS patients. The administration of an antidepressant that inhibits the reuptake of serotonin in IBS patients suppresses hyperactivity of the anterior cingulate cortex [23] and improves clinical IBS symptoms [24].…”

Um marcador anatômico e a proposta de tratamento cirúrgico na síndrome do cólon irritável

“…Fatores culturais e decorrentes de hábitos alimentares têm sido isolados com sugestões de agentes etiológicos. 25,26 Hiperalgesia visceral, estresse, abuso físico e sexual têm sido elementos associados como participantes do conjunto de dados clínicos, englobado no universo dessa moléstia [1][2][3][4][5][6][7][8][9] , da mesma forma ocorrendo com as enterites bacterianas e virais, sem que, no entanto, seja possível destacar um elemento marcador. 27,28 São tantas as teorias e complexas as investigações e conclusões que a SCI passa a ser vista sob um conjunto heterogêneo de desordens com sintomas parecidos, mas de diferentes etiologias [29][30][31][32] que retroalimentam mais especulações sobre uma causa básica, o que, sem dúvida alguma, favorece a " medicalização" e a emergência de procedimentos subsidiados pela medicina alternativa 33 .…”

“…Apesar de ser comum, com incidência populacional de até 30% (predominando nas mulheres), e de ser alvo de estudos com destaque para diversos hormônios de ação gastrintestinal [3][4][5][6][7][8][9][10][11] , o diagnóstico e o tratamento dessa doença nem sempre são tarefas fáceis de serem executadas, sobretudo pela falta de um marcador que defina sua natureza, não só para retirá-la da classe de " doença de diagnóstico de exceção", como para permitir opções terapêuticas efetivas. 12,13 Baseados na observação de que a Síndrome do ceco móvel (SCM) engloba sintomas que se superpõem aos da SCI 14 nossos objetivos, ao desenvolver um estudo prospectivo não casualizado, foram: a. demonstrar a relação de causa e efeito entre o ceco móvel e a SCI, b. avaliar o resultado da cecopexia, como método de tratamento de pacientes com Síndrome do cólon irritável (SCI) ou com desconforto abdominal de etiologia desconhecida; e c. mostrar que o ceco móvel pode ser considerado como o primeiro marcador anatômico para a SCI.…”