Cited by 60Gut microbiota and healthInflammatory Bowel DiseaseGenomics, phytochemicals, and oxidative stress

Dietary AhR Ligands Regulate AhRR Expression in Intestinal Immune Cells and Intestinal Microbiota Composition

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Schanz, Oliver, Chijiiwa, Rieka, Cengiz, Sevgi Can, Majlesain, Yasmin, Weighardt, Heike, Takeyama, Haruko, Förster, Irmgard·2020·International Journal of Molecular Sciences

Abstract

A diet rich in vegetables and fruit is generally considered healthy because of a high content of phytochemicals, vitamins, and fiber. The phytochemical indole-3-carbinol (I3C), a derivative of glucobrassicin, is sold as a dietary supplement promising diverse health benefits. I3C metabolites act as ligands of the aryl hydrocarbon receptor (AhR), an important sensor for environmental polyaromatic chemicals. Here, we investigated how dietary AhR ligand supplementation influences AhR target gene expression and intestinal microbiota composition. For this, we used AhR repressor (AhRR)-reporter mice as a tool to study AhR activation in the intestine following dietary I3C-supplementation in comparison with AhR ligand-deprived diets, including a high fat diet. AhRR expression in intestinal immune cells was mainly driven by dietary AhR ligands and was independent of microbial metabolites. A lack of dietary AhR ligands caused enhanced susceptibility to dextran sodium sulfate (DSS)-induced colitis and correlated with the expansion of Enterobacteriaceae, whereas Clostridiales, Muribaculaceae, and Rikenellaceae were strongly reduced. I3C supplementation largely reverted this effect. Comparison of I3C-induced changes in microbiota composition using wild-type (WT), AhRR-deficient, and AhR-deficient mice revealed both AhR-dependent and -independent alterations in the microbiome. Overall, our study demonstrates that dietary AhR ligand supplementation has a profound influence on Ahrr expression in intestinal immune cells as well as microbiota composition.

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  • Environmental differences such as diet, ligand amount in diet, bedding, caging, or facility pathogens can influence observed phenotypes in Ahr null mice.

    “Differences in the environment such as diet, amount of ligand in the diet, bedding, caging, or the presence of pathogens in the facility can influence observed phenotypes.”

    From Rodent Genetic Models of Ah Receptor Signaling (2021) · cites this paper as Schanz et al., 2020

    The Results (§2.4; page unavailable) show that diet and AhR-ligand supplementation change gut microbial composition, including some responses specific to AhR-null mice. The Discussion (§3; page unavailable) also warns that diet comparisons can confound observed AhR-signaling effects. The paper does not establish that bedding, caging, or facility pathogens influence those phenotypes; its discussion of a specific-pathogen-free facility concerns possible differences in commensal bacteria. (LLM, conf=0.88)

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  • Dietary ligands can influence the microbiome and AHR signaling.

    “These environmental considerations are particularly important as it is now known that ligands obtained through the diet can influence microbiome and AHR signaling, and it is also likely that differences in pathogens can affect immune output in laboratory mice (Brawner et al., 2019; Leavy, 2011; Schanz et al., 2020).”

    From Rodent Genetic Models of Ah Receptor Signaling (2021) · cites this paper as Schanz et al., 2020

  • Differences in pathogens can affect immune output in laboratory mice.

    “These environmental considerations are particularly important as it is now known that ligands obtained through the diet can influence microbiome and AHR signaling, and it is also likely that differences in pathogens can affect immune output in laboratory mice (Brawner et al., 2019; Leavy, 2011; Schanz et al., 2020).”

    From Rodent Genetic Models of Ah Receptor Signaling (2021) · cites this paper as Schanz et al., 2020

    The Discussion (page unavailable) considers whether commensal bacteria in the authors’ specific-pathogen-free facility affect AhR signaling, and the Results report immune differences associated with diet. Neither passage addresses whether differences in pathogens affect immune output in laboratory mice. Searches for pathogen differences and immune responses found no passage making that point. (LLM, conf=0.73)

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Authors
Schanz, O., Chijiiwa, R., Cengiz, S. C., Majlesain, Y., Weighardt, H., Takeyama, H., & Förster, I.
Affiliations
  • University of Bonn (DE)
  • Waseda University (JP)
Corresponding author
  • Weighardt, Heike
  • Takeyama, Haruko
  • Förster, Irmgard
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2020-04-30
Volume
21
Issue
9
Pages
3189
ISSN
1422-0067 (ISSN-L)
OpenAlex
W3023164985
Cited by
60
References
4
Citations by year
2026: 5 · 2025: 9 · 2024: 9 · 2023: 10 · 2022: 11 · 2021: 11 · 2020: 4 · 2019: 1
FWCI
2.92
Type
journal article
Language
en
Open access
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Deutsche Forschungsgemeinschaft (EXC 2151-Project No. 390873048)
  • Jürgen Manchot Foundation (MOI-P14, PhD stipend Majlesain)
  • Ministry of Education, Culture, Sports, Science and Technology (Top Global University Project)
  • Innovation Advancement Organization, Japan (H.T.)
  • Deutscher Akademischer Austauschdienst (Short-Term Grants, 2019 (57440917))
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
Keywords
aryl hydrocarbon receptor, indole-3-carbinol, intestinal immune cells, gut microbiota, DSS-induced colitis, Enterobacteriaceae, high-fat diet, phytochemicals
MeSH terms
Gastrointestinal Microbiome, Animals, Colitis, Female, Flow Cytometry, Indoles, Male, RNA, Ribosomal, 16S, Dextran Sulfate, Receptors, Aryl Hydrocarbon, Mice, Real-Time Polymerase Chain Reaction

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