Tryptophan-kynurenine metabolism: a link between the gut and brain for depression in inflammatory bowel disease

Abstract

Inflammatory bowel disease (IBD), which mainly includes ulcerative colitis (UC) and Crohn's disease (CD), is a group of chronic bowel diseases that are characterized by abdominal pain, diarrhea, and bloody stools. IBD is strongly associated with depression, and its patients have a higher incidence of depression than the general population. Depression also adversely affects the quality of life and disease prognosis of patients with IBD. The tryptophan-kynurenine metabolic pathway degrades more than 90% of tryptophan (TRP) throughout the body, with indoleamine 2,3-dioxygenase (IDO), the key metabolic enzyme, being activated in the inflammatory environment. A series of metabolites of the pathway are neurologically active, among which kynerunic acid (KYNA) and quinolinic acid (QUIN) are molecules of great interest in recent studies on the mechanisms of inflammation-induced depression. In this review, the relationship between depression in IBD and the tryptophan-kynurenine metabolic pathway is overviewed in the light of recent publications.

Dual Role of Indoles Derived From Intestinal Microbiota on Human Health

“…A recent study shows that, IAA, an indole derivative, can alleviate ankylosing spondylitis in mice by restoring intestinal microflora balance and decreasing the inflammatory response (158). Indoles have beneficial effects on human health, modulating the intestinal barrier and helping to maintain intestinal homeostasis by activating immune cells to release anti-inflammatory factors such as IL-22 (58), inhibiting the colonization of pathogenic bacteria including EHEC (31), inducing gene expression of TJs and AJ to reduce intestinal permeability (96), and increasing MUC expression to enhance mucus barrier function (22). Mainly, indoles in the regulation of intestinal microecology also play a key role.…”

“…3) the serotonin pathway (1-2%) (Figure 1). Most of the existing reviews focus on Trp (17)(18)(19) and kynurenine (20)(21)(22), and few reviews systematically describe the properties of indoles (23).…”

Molecular Basis Underlying the Therapeutic Potential of Vitamin D for the Treatment of Depression and Anxiety

“…The activation of this enzyme increases the formation of quinolinic acid, an N-methyl-D-aspartate (NMDA) receptor agonist, through the kynurenine pathway, contributing to glutamatergic system disturbance and compromising the synthesis of serotonin by depleting tryptophan [8,[29][30][31]. Within this scenario, it is worth noting that more than 90% of the body's serotonin is produced in the gut, particularly by enterochromaffin cells, and alterations in the intestinal microbiota triggered by inflammatory processes have been shown to directly compromise the synthesis of this monoamine [32,33]. Indeed, it is important to note that changes in gut microbiota have been reported to impair the efficacy of antidepressants, such as fluoxetine [34].…”

Targeting the Gut Microbiome in Prader-Willi Syndrome

“…Therefore, targeting the gut microbiome is being actively investigated as a therapeutic strategy not only for obesity but also for mental health symptoms. In this regards, microbial regulation of tryptophan metabolism, specifically the tryptophan-kynurenine pathway, is being extensively investigated as a mediator of the impact of the gut microbiome on mental health [21][22][23][24].…”