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Aryl hydrocarbon receptor and immunity: Activation by diet, microbiota and probiotics

This project was part of a Joint programming Initiative on Healthy Diet for a Healthy Life, involving 3 partner organisations (1). Dr Harry Sokol at Sokol from the French National Institute for Agricultural Research (INRA) and the French Medical Research Institute (INSERM), (2) Dr Elena Verdu, Famcombe Family Digestive Health Research Institute at McMaster University, Canada and (3) Prof Jerry Wells, Wageningen University and Research, The Netherlands.

The intestinal metabolism of tryptophan, an essential amino acid and important component of our diet is perturbed in intestinal diseases (such as inflammatory bowel disease and irritable bowel syndrome), but also in some non-intestinal diseases. In the gut, tryptophan can be transformed by certain intestinal bacteria into several molecules some of which promote a healthy intestine and immune system through interaction with a host receptor called the arylhydrocarbon receptor (AhR).

In this project we obtained further evidence that a harmless Lactobacilus bacterium with a strong and natural ability to produce beneficial metabolites of tryptophan or the metabolites themselves, can have beneficial effects in certain diseases where the gut bacteria have a reduced capacity to produce tryptophan metabolites interacting with AhR.

Results of AryImune

AhR signalling orchestrates immune responses at barrier sites such as the gut mucosa, promoting tolerance, intra-epithelial lymphocytes (IEL), organogenesis of intestinal lymphoid follicles, T cells and innate lymphoid cells (ILCs) group 3, that produce IL-17 and IL-22,16 all of which could have an impact on gut barrier function and intestinal inflammatory diseases where the microbiota has a reduced capacity to produce AhR ligands. The aims of the project were to identify AhR-activating microorganisms, or their tryptophan metabolites and assess their health effects including a clinical trial in human subjects performed in Canada.

Lactobacillus species (commonly used as probiotics) vary in their capacity to produce AhR activating ligands in vitro and L. reuteri strains were among the highest producers. The selected Lactobacillus strains had no significant effect on the severity of colitis or C. rodentium infection in vivo. However, administration of indoles (found in cruciform vegetables) in the diet increased AhR activation activity in faecal extracts and reduced disease activity. Results of the human trial are still being analysed but indicate that high-tryptophan diets increase AhR activating metabolites in some subjects.

Verslagen


Eindverslag

Dit project maakte onderdeel uit van een gezamenlijk programma gericht op Gezond Dieet – Gezond Leven. Drie verschillende partner organisaties waren betrokken bij dit project, te weten 1) Dr Harry Sokol van het Franse INRA (Institute National de la Recherche Agronomique) en INSERM (Institut National de la Santé et de la Recherche Médicale) in Parijs, 2) Dr Elena Verdu, Famcombe Family Digestive Health Research Institute aan de McMaster Universiteit in Canada, en 3) Prof Jerry Wells, van de Wageningen Universiteit, Nederland. Tryptofaan is een essentieel aminozuur en een belangrijke component in ons dieet. Het metabolisme van tryptofaan in de darm is verstoord bij darmaandoeningen zoals chronische darmontsteking (IBD) en prikkelbare darmsyndroom (IBS), maar ook bij enkele niet darm-gerelateerde aandoeningen. In de darm wordt tryptofaan door bepaalde bacteriën die daar aanwezig zijn omgezet in andere moleculen (metabolieten) waarvan er een aantal een gezonde darm en gezond immuunsysteem bevorderen door de interactie met een receptor van de gastheer. Deze receptor heet de aryl hydrocarbon receptor (AhR). In dit project hebben we bewijs verzameld dat een onschadelijke Lactobacillus bacterie, waarvan bekend is dat deze tryptofaan kan omzetten in verschillende metabolieten, gezondheid bevorderende effecten kan hebben bij bepaalde ziekten, waarbij de aanwezige darm bacteriën moeite hebben met het produceren van de metabolieten van tryptofaan die aan de AhR kunnen binden.
Bacteria in the gut have recently been shown to produce specific dietary compounds that promote a healthy gut through interactions with immune system. The mechanism involves interaction of these compounds with the aryl hydrocarbon receptor (AhR). We have screened intestinal and probiotic strains of bacteria to identify those that produce compounds interacting with AhR. The best producers are now being characterised and tested for their health effects.

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  • Voeding
  • Darmen

    • Kenmerken

    • Projectnummer:
      529051009
    • Looptijd: 100%
      2016
      2020
    • Gerelateerde programma's:
    • Gerelateerde subsidieronde:
      Intestinal Microbiom ics
    • Projectleider en penvoerder:
      Prof. dr. J.M. Wells
    • Verantwoordelijke organisatie:
      Wageningen Universiteit