An Insight into the Roles of Dietary Tryptophan and Its Metabolites in Intestinal Inflammation and Inflammatory Bowel Disease

Abstract

Inflammatory bowel disease (IBD) is complex, chronic, and relapsing gastrointestinal inflammatory disorders, which includes mainly two conditions, namely ulcerative colitis (UC) and Crohn's disease (CD). Development of IBD in any individual is closely related to his/her autoimmune regulation, gene‐microbiota interactions, and dietary factors. Dietary tryptophan (Trp) is an essential amino acid for intestinal mucosal cells, and it is associated with the intestinal inflammation, epithelial barrier, and energy homeostasis of the host. According to recent studies, Trp and its three major metabolic pathways, namely kynurenine (KYN) pathway, indole pathway, and 5‐hydroxytryptamine (5‐HT) pathway, have vital roles in the regulation of intestinal inflammation by acting directly or indirectly on the pro/anti‐inflammatory cytokines, functions of various immune cells, as well as the intestinal microbial composition and homeostasis. In this review, recent advances in Trp‐ and its metabolites‐associated intestinal inflammation are summarized. It further discusses the complex mechanisms and interrelationships of the three major metabolic pathways of Trp in regulating inflammation, which could elucidate the value of dietary Trp to be used as a nutrient for IBD patients.

Some CSF Kynurenine Pathway Intermediates Associated with Disease Evolution in Amyotrophic Lateral Sclerosis

“…Apart from KP and serotonin, TRP is also catabolized by another metabolic pathway: Direct metabolism into indole and derivates by the gut microbiota [ 31 ]. Indole metabolites, like indole-3-acetic acid, also participate in immune regulation [ 8 ]. To the best of our knowledge, no previous study has investigated the relationship between ALS and these indole intermediates in CSF.…”

“…In the context of inflammation, larger amounts of NAD+ are needed by immune cells. To meet this requirement, IDO-1 expression is upregulated by proinflammatory cytokines, mainly interferon gamma (IFN-γ), interferon alpha (IFN-α), and interleukin 6 (IL-6) [ 7 , 8 , 9 ]. Activation of IDO-1 and production of KP intermediates in turn have immunomodulatory effects [ 8 , 9 ].…”

“…To meet this requirement, IDO-1 expression is upregulated by proinflammatory cytokines, mainly interferon gamma (IFN-γ), interferon alpha (IFN-α), and interleukin 6 (IL-6) [ 7 , 8 , 9 ]. Activation of IDO-1 and production of KP intermediates in turn have immunomodulatory effects [ 8 , 9 ]. Contrasting with TRP and kynurenine which cross the blood–brain barrier and can be elevated in cerebrospinal fluid (CSF) after systemic inflammation, KYNA and QUIN cross this barrier poorly, are produced locally in situ from kynurenine, and their elevation reflects neuroinflammation [ 7 ].…”

An Investigation into the Temporal Reproducibility of Tryptophan Metabolite Networks Among Healthy Adolescents

“…There is cross-talk 12 , 13 and a balanced interplay 14 among these aforementioned pathways. Interestingly, the microbial production of indoles influences the host-derived pathways 15 and provides a metabolic balance between the host-derived pathways.…”

Nutrition—or Lack Thereof—As a Source of Gut Inflammation: Evidence from Basic Science and Clinical Studies

“…[ 3 ] Among the most prominent “postbiotics” are short‐chain fatty acids, polyamines, secondary bile acids, bacterial polysaccharides, vitamins, and other micronutrients reviewed by Kundra and colleagues, [ 4 ] and tryptophan metabolites, namely indole derivates reviewed by Li and colleagues. [ 5 ] Recently developed experimental models such as intestinal epithelial organoids or “glued caved cylinders” nowadays allow reproducible mechanistic and toxicological ex vivo studies on the biological effects of potentially beneficial “postbiotics” prior to their use in animal and human in vivo studies. Postbiotics as opposed to probiotics do not bear the risk of further propagating inflammation or horizontal antibiotic resistant gene transfer, a major concern with probiotics, and thus are perfectly suited for therapeutic interventions in diseased patients.…”