Inflammation in the intestine results from the net effect of genetics, nutritional status, the microbiome that converge to influence multiple inflammatory signaling pathways. Some existing data suggests that L-tryptophan can promote remission, yet little is known of the mechanisms involved in protection derived from L-tryptophan. One possible mechanism may involve serotonin, a tryptophan metabolite that affects the expression of serotonin receptors. A recent study by Wang and colleagues investigated the impact of tryptophan on serotonin receptor-mediated responses of the gut immune system and the results are published in the July 2020 issue of The Journal of Nutrition.
In the first experiment, male mice were assigned to the control group or received daily supplementation of L-tryptophan in water (0.1 mg/g body weight), and half of each group were exposed to 2% DSS to induce colitis during days 8-14 of the 17-day study. In the second and third experiments, the mice were treated with tryptophan and DSS, or just DSS and administered serotonin receptor antagonists (HRT1A and HRT4) or an agonist (HRT2). Immune cell phenotype, inflammatory mediators and related signaling molecules were monitored. The expression of tryptophan hydroxylase, a serotonin reuptake transporter, and, serotonin receptors was determined.
Providing tryptophan prior to DSS administration increased the expression of a serotonin reuptake transporter, and two serotonin receptors, but decreased the expression of another serotonin receptor. The level of serotonin in the colon was decreased. Tryptophan attenuated the activation of toll-like receptor 4 signaling and nuclear p-65 that had been induced by DSS administration. The effects of tryptophan were reversed by the administration of HRT2 agonist or HRT1A and HRT4 antagonists. These observations led the authors to conclude that tryptophan reduces colonic immune responses by reducing serotonin levels that decrease interactions with HRT1A and HRT4.
In a commentary on this article, Alvarado and Ciorba concur that this work demonstrates the ability of prophylactically administered tryptophan to reduce colitis through its impact on serotonin receptor signaling. They suggest the work does not address whether tryptophan would suppress ongoing disease and that although its effects through serotonin signaling are supported, that the work does not exclude effects resulting from kynurenine or microbially-derived indoles. Even though the serotonin-receptor signaling was not always consistent, Alvarado and Ciorba concluded that more work is needed to determine if modulation of serotonin receptor subtypes might serve as a therapeutic approach.
References Wang B, Sun S, Liu M, Chen H, Liu N, Wu Z, Wu G, Dai Z. Dietary L-tryptophan regulates colonic serotonin homeostasis in mice with dextran sodium sulfate-induced colitis. The Journal of Nutrition, Volume 150, Issue 7, July 2020, Pages 1966–1976, https://doi.org/10.1093/jn/nxaa129.
Alvarado DM, Ciorba MA. Serotonin receptors regulate inflammatory response in experimental colitis. The Journal of Nutrition, Volume 150, Issue 7, July 2020, Pages 1678–1679, https://doi.org/10.1093/jn/nxaa160.
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