Dietary tryptophan alleviates dextran sodium sulfate-induced colitis through aryl hydrocarbon receptor in mice

Islam, Jahidul; Sato, Shoko; Watanabe, Kouichi; Watanabe, Takahito; Ardiansyah, Ardiansyah; Hirahara, Keisuke; Aoyama, Yukihide; Tomita, Shuhei; Aso, Hisashi; Komai, Michio; Shirakawa, Hitoshi

doi:10.1016/j.jnutbio.2016.12.019

Cited by 164 publications

(142 citation statements)

References 40 publications

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“…The metabolism of tryptophan by certain gut bacteria has been shown to generate indole metabolites that exhibit both AhR agonistic and partial antagonistic activities . Furthermore, tryptophan supplementation in the diet of mice resulted in the production of tryptophan metabolites, which attenuated colitis in an AhR‐dependent fashion …”

Section: Resultsmentioning

confidence: 99%

“…Certain dietary compounds like polyphenols, mainly flavonoids, and tryptophan derivatives have been reported as AhR ligands . Recent studies showed the major significance of dietary compounds like tryptophan and phytochemicals like indole‐derivatives in both intestinal and microbial homeostasis in relation to AhR in mouse colitis models . As little is known about how metabolism of these compounds by microbes alters the AhR‐mediated signaling activity, we sought to study the kinetics of their release and the ability to activate the AhR using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME), simulating the ascending (AC), transverse (TC), and descending (DC) colon .…”

Section: Introductionmentioning

confidence: 99%

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Polyphenols and Tryptophan Metabolites Activate the Aryl Hydrocarbon Receptor in an in vitro Model of Colonic Fermentation

Koper

Loonen

Wells

et al. 2018

Molecular Nutrition Food Res

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Scope Many dietary phytochemicals have been reported to promote gut health. Specific dietary phytochemicals, such as luteolin, as well as specific microbial metabolites of tryptophan are ligands of the aryl hydrocarbon receptor (AhR), which plays a role in immunity and homeostasis of the gut barrier. Here, the fate of luteolin during colonic fermentation and the contribution of tryptophan metabolites to AhR activity in different parts of the colon are investigated. Methods and results Several polyphenols are screened for AhR activation and oregano, containing the ligand luteolin, is added to batch cultures of human microbiota from the distal colon. Luteolin is rapidly metabolized, with no measurable increase in AhR activity. In the second experiment, using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME), not all luteolin is metabolized in the ascending colon, but disappear rapidly in the transverse colon. The greatest AhR activity is due to microbiota‐derived metabolites of tryptophan, particularly in the descending colon. Conclusions Luteolin in food is rapidly metabolized in the transverse colon. Tryptophan metabolism by the microbiota in the colon contributes substantially to the pool of lumen metabolites that can activate the AhR.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Polyphenols and Tryptophan Metabolites Activate the Aryl Hydrocarbon Receptor in an in vitro Model of Colonic Fermentation

Koper

Loonen

Wells

et al. 2018

Molecular Nutrition Food Res

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“…Trp is also a functional AA, which serves as a vital regulator of the metabolic pathway and reacts with ligands to effectively protect host health (Hisamatsu et al, 2012;Kim et al, 2010;Palego, Betti, Rossi, & Giannaccini, 2016;Shizuma, Mori, & Fukuyama, 2013). In the GI tract, Trp can enter several metabolic pathways under the action of gut microbes and also interact closely with the immune system (Islam et al, 2017). Among these pathways, the protein synthesis, serotonin (5-hydroxytryptamine, 5-HT), kynurenine, and microbiota-mediated degradation pathways (Keszthelyi, Troost, & Masclee, 2009;Ma et al, 2018;Zelante et al, 2013) are the most notable.…”

Section: Tryptophan Microbiota and The Immune Systemmentioning

confidence: 99%

Dietary Amino Acids and the Gut‐Microbiome‐Immune Axis: Physiological Metabolism and Therapeutic Prospects

2018

Comp Rev Food Sci Food Safe

190

122

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Dietary amino acids (AAs) are not only absorbed and metabolized by enterocytes but also available to the microbiota in the gut in mammals. In addition to serving as the materials for protein synthesis, AAs can act as precursors for numerous metabolic end products in reactions involving the intestinal mucosa and microbiota. After penetrating the epithelial barrier, microbial metabolites can enter and accumulate in the host circulatory system, where they are sensed by immune cells and then elicit a wide range of biological functions via different receptors and mechanisms. Some intestinal bacteria can also synthesize certain AAs, implying that the exchange of AAs between hosts and microorganisms is bidirectional. Changes in AA composition and abundance can affect AA‐metabolizing bacterial communities and modulate macrophages and dendritic cells via toll‐like receptors (TLRs), autoinducer‐2 (AI‐2), and NOD‐like receptors (NLRs), and also regulate the gut‐microbiome‐immune axis via aryl hydrocarbon receptor (AhR), serotonin/5‐hydroxytryptamine (5‐HT), and other signaling pathways, all of which play critical roles in regulating the intestinal mucosal immunity and microbiota directly or indirectly, contributing to intestinal homeostasis. Therefore, the current findings of the effects of certain functional AAs on the gut‐microbiome‐immune axis are reviewed, illustrating signaling pathways of tryptophan (Trp), glutamine (Gln), methionine (Met), and branched‐chain AAs (BCAAs) in the intestinal barrier and regarding immunity via crosstalk with their receptors or ligands. These findings have shed light on the clinical applications of dietary AAs in improving gut microbiota and mucosal immunity, therefore benefiting the gut as well as local and systemic health.

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“…AHR also plays a unique role in regulating adaptive cell immunity (21)(22)(23), including the CD39-dependent induction of Tregs (24). Alterations in the AHR pathway of activation are linked to chronic inflammation in IBD patients (25) and AHR deletion results in exacerbations of DSS-induced colitis (26,27). Further, it has recently been shown that DSS-induced colitis is worsened upon reconstitution of RAG-2/IL2RG-deficient mice with T cells derived from Ahr d mice (28) expressing an AHR molecule of reduced affinity (21).…”

Section: Introductionmentioning

confidence: 99%

Bilirubin suppresses Th17 immunity in colitis by upregulating CD39

et al. 2017

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Dietary tryptophan alleviates dextran sodium sulfate-induced colitis through aryl hydrocarbon receptor in mice

Cited by 164 publications

References 40 publications

Polyphenols and Tryptophan Metabolites Activate the Aryl Hydrocarbon Receptor in an in vitro Model of Colonic Fermentation

Polyphenols and Tryptophan Metabolites Activate the Aryl Hydrocarbon Receptor in an in vitro Model of Colonic Fermentation

Dietary Amino Acids and the Gut‐Microbiome‐Immune Axis: Physiological Metabolism and Therapeutic Prospects

Bilirubin suppresses Th17 immunity in colitis by upregulating CD39

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