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Background

Tryptophan is an essential amino acid that is transformed by host and gut microbial enzymes into multiple bioactive metabolites that regulate immunity, mood and circadian rhythms. In particular, indoles, produced by gut bacterial metabolism of tryptophan, have recently gained central attention. Indoles are activators of the aryl hydrocarbon receptor (AhR), which is crucial for the maintenance of intestinal homeostasis and immunity. Tryptophan supplementation in fortified foods have been advocated to prevent chronic inflammatory conditions, from autism to chronic inflammation. However, whether dietary tryptophan supplementation affects immune function, tryptophan metabolic pathways and gastrointestinal symptoms in healthy subjects, is unknown.

Aims

To assess whether tryptophan supplementation, in healthy subjects on a low tryptophan diet, induces changes in microbiota-derived metabolites (indoles), host cytokine production or gut symptoms.

Methods

We performed a randomized, double blind, placebo-controlled, crossover study in 20 healthy individuals, between 18 and 75 years old, following a regular diet. Subjects were instructed to start a standardized low tryptophan diet and were randomly assigned to a 3-week tryptophan supplement (3gr/day) or placebo. After a 2-week washout period, subjects were crossed over to the opposite 3-week intervention arm. Self-administered questionnaires (GSRS, DASS21 and HADS) were used to assess gastrointestinal symptoms and mood/anxiety/stress. Stool, urine and blood samples were collected to measure tryptophan metabolites (kynurenine pathway and indoles) and cytokines …