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Activation of the Ah Receptor Modulates Gastrointestinal Homeostasis and the Intestinal Microbiome

  • Gulsum E. Muku
  • Iain A. Murray
  • Gary H. PerdewEmail author
Microbiome (A Patterson, Section Editor)
  • 10 Downloads
Part of the following topical collections:
  1. Topical Collection on Microbiome

Abstract

Purpose of Review

The Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that responds to a variety of structurally diverse exogenous and endogenous small molecules. The AHR has been implicated in both host and microbiota homeostasis. Understanding the role of the AHR in gastrointestinal health and the appropriate level of AHR activation has implications in determining whether the AHR is an appropriate target for dietary or drug intervention.

Recent Findings

The discovery of previously unrecognized AHR ligands of dietary, environmental, and pharmaceutical origin continues to expand, including many tryptophan derivatives (e.g., 2-oxindole, kynurenic acid). AHR activation can lead to organ and cell type-specific effects through altered gene expression. Most recent studies have focused on the role of the AHR in immune cell function especially within the gastrointestinal tract. The AHR plays an important role in xenobiotic metabolism within the intestine. In addition, the AHR regulates proliferation and differentiation status of intestinal epithelial cells. The lack of AHR expression and activation of the AHR are both capable of altering the composition of the gut microbiota in mice. Dietary AHR ligand exposure has been shown to attenuate toxicity due to gastrointestinal challenge. However, activation by persistent AHR ligands can lead to intestinal dysfunction.

Summary

Many questions remain to be answered as to the suitability of utilizing the AHR as a target to maintain gastrointestinal health and treat various disease states. Nevertheless, the potential of AHR ligands to improve intestinal health appears to be quite significant.

Keywords

Ah receptor IL-22 Aryl hydrocarbon Intestine CYP1A1 TCDD 

Notes

Acknowledgments

We thank Marcia H. Perdew for excellent editorial assistance.

Funding Information

This work was supported by the National Institutes of Health Grants ES028244 (GHP) and the USDA National Institute of Food and Federal Appropriations under Project PEN04607 and Accession number 1009993.

Compliance with Ethical Standards

Conflict of Interest

Gulsum E. Muku, Iain A. Murray and Gary H. Perdew declare no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Veterinary and Biomedical Sciences and The Center for Molecular Toxicology and CarcinogenesisThe Pennsylvania State UniversityUniversity ParkUSA

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