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

JPI HDHL “Intestinal Microbiomics” (IM2015)
Aryl hydrocarbon receptor and immunity: Activation by diet, microbiota and probiotics
Harry Sokol


Partner Organization Partner Country
Farncombe Family Digestive Health Research Institute at McMaster UniversityCanada
French National Institute for Agricultural Research (INRA)France
University WageningenThe Netherlands

1. Overall project description

1.1 Summary

Aims: The aryl hydrocarbon receptor (AhR) is a transcription factor recently shown to be crucial for the maintenance of intestinal homeostasis, however its precise gut luminal activators and functional consequences are unknown. Activators originate from (i) the diet, such as indole-3-carbinol from cruciferous vegetables, (ii) the microbiota, (iii) lactic acid bacteria, used in food or as probiotics, that produce AhR agonists from catabolism of tryptophan. The overall aim of our project is to assess the effects of AhR activation by microbiota-derived components on intestinal immunity and physiology. We will specifically determine the dietary-microbiota interactions that lead to AhR activation and identify AhR-activating microorganisms, or their metabolites, with potential health benefits.

Achievements: Before starting the project, a consortium agreement has been signed between all the academic and industrial partners on november 2016. Three post docs have been hired for the project. The screening of probiotic strains for their ability to produce AhR agonists is completed and 3 candidates have been selected for in vivo studies in 3 pathological models. The clinical trial design has been approved by regulatory agencies in Canada. The study started on October 2017 and 10 participants have already been recruited.

Expected Impact: We expect to better understand the host-microbiota crosstalk in health and disease and identify new dietary strategies to modulate AhR signalling to maintain gut health and alleviate intestinal inflammation

1.2 Highlights

We identified an alteration in the gut microbiota function in Coeliac disease in human characterized by an impaired production of aryl hydrocarbon receptor (AhR) agonists. In Coeliac disease mouse models, correcting this alteration using a pharmacologic approach (adminstration of AhR agonists) or by using intestinal bacteria naturally producing AhR agonists alleviated the severity of the gluten immunopathology in the mouse model. 

4. Impact

4.1 List of publications

AuthorsTitleYear, Issue, PPPartners NumberDoiPdf
Lamas B, Natividad J, Sokol H (first and last authors are Partners)Aryl hydrocarbon receptor and intestinal immunity10.1038/s41385-018-0019-2 Download
Agus A, Planchais J, Sokol H (Second and third authors are Partners)Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease10.1016/j.chom.2018.05.003 Download

4.2 Presentation of the project

Target groupAuthorsMeans of communicationHyperlinkPdf
Scientist sand physicianVerdu E., Environmental factors: update on the role of gut microbiota in celiac disease, International Celiac disease symposium, Paris, 2019oral presentation
ScientistsVerdu E., , Keystone symposia, Microbiome and Celiac disease Ireland, 2019oral presentation
Verdu E., Gut microbiota in celiac disease, International Celiac disease symposium, New York, 2020oral presentation

4.3 List of submitted patents and other outputs

Patent licencePartners involvedYearInternational eu or national patentCommentPdf

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This project has received funding from the European Union’s
H2020 Research and Innovation Programme under grant agreement n.696300

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