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Mixture Effects of Tryptophan Intestinal Microbial Metabolites on Aryl Hydrocarbon Receptor Activity

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F22%3A73614401" target="_blank" >RIV/61989592:15310/22:73614401 - isvavai.cz</a>

  • Result on the web

    <a href="https://www.mdpi.com/1422-0067/23/18/10825/htm" target="_blank" >https://www.mdpi.com/1422-0067/23/18/10825/htm</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.3390/ijms231810825" target="_blank" >10.3390/ijms231810825</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Mixture Effects of Tryptophan Intestinal Microbial Metabolites on Aryl Hydrocarbon Receptor Activity

  • Original language description

    Aryl hydrocarbon receptor (AHR) plays pivotal roles in intestinal physiology and pathophysiology. Intestinal AHR is activated by numerous dietary, endogenous, and microbial ligands. Whereas the effects of individual compounds on AHR are mostly known, the effects of real physiological mixtures occurring in the intestine have not been studied. Using reporter gene assays and RT-PCR, we evaluated the combinatorial effects (3520 combinations) of 11 microbial catabolites of tryptophan (MICTs) on AHR. We robustly (n = 30) determined the potencies and relative efficacies of single MICTs. Synergistic effects of MICT binary mixtures were observed between low- or medium-efficacy agonists, in particular for combinations of indole-3-propionate and indole-3-lactate. Combinations comprising highly efficacious agonists such as indole-3-pyruvate displayed rather antagonist effects, caused by saturation of the assay response. These synergistic effects were confirmed by RT-PCR as CYP1A1 mRNA expression. We also tested mimic multicomponent and binary mixtures of MICTs, prepared based on the metabolomic analyses of human feces and colonoscopy aspirates, respectively. In this case, AHR responsiveness did not correlate with type of diet or health status, and the indole concentrations in the mixtures were determinative of gross AHR activity. Future systematic research on the synergistic activation of AHR by microbial metabolites and other ligands is needed.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    10608 - Biochemistry and molecular biology

Result continuities

  • Project

    Result was created during the realization of more than one project. More information in the Projects tab.

  • Continuities

    P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Others

  • Publication year

    2022

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

  • ISSN

    1422-0067

  • e-ISSN

    1422-0067

  • Volume of the periodical

    23

  • Issue of the periodical within the volume

    18

  • Country of publishing house

    CH - SWITZERLAND

  • Number of pages

    15

  • Pages from-to

    "10825-1"-"10825-15"

  • UT code for WoS article

    000856436800001

  • EID of the result in the Scopus database

    2-s2.0-85138908033