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Record W4413139630 · doi:10.1016/j.phrs.2025.107909

The aryl hydrocarbon receptor: A promising target for intestinal fibrosis therapy

2025· article· en· W4413139630 on OpenAlexaff
Yiyang Pan, Ying Deng, Hua Yang, Min Yu

Bibliographic record

VenuePharmacological Research · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicDigestive system and related health
Canadian institutionsMontreal Clinical Research Institute
FundersNational Key Research and Development Program of ChinaNatural Science Foundation of ChongqingMinistry of Science and Technology of the People's Republic of ChinaNatural Science Foundation Project of Chongqing, Chongqing Science and Technology CommissionNational Natural Science Foundation of China
KeywordsAryl hydrocarbon receptorFibrosisGut floraBiologyTranscription factorImmunologyMedicineInternal medicineBiochemistry

Abstract

fetched live from OpenAlex

Intestinal fibrosis, a severe complication of inflammatory bowel disease, leads to intestinal stenosis. Effective therapies for this condition are lacking. The aryl hydrocarbon receptor (AhR), a highly conserved nuclear transcription factor activated by diverse ligands, plays dual roles in fibrogenesis, but its relationship to intestinal fibrosis has not been comprehensively reviewed. This review explores the pathogenesis of intestinal fibrosis, and places particular focus on the mechanistic role of AhR signaling pathways, which may be mediated by dietary, microbial, and environmental ligands. We propose a new strategy for the targeting of AhR-related dietary ligands to prevent intestinal fibrosis. Dietary AhR ligands, such as glucobrassicin, flavonoids, and curcumin, exert anti-fibrotic effects by modulating the gut microbiota, suppressing collagen deposition, and inhibiting transforming growth factor-β pathways. Conversely, environmental pollutants (e.g., polycyclic aromatic hydrocarbons, microplastics, and propiconazole) exacerbate fibrosis via AhR activation. In multiple disease models, 16S rRNA sequencing has revealed positive and negative linear relationships between the gut microbiota and fibrosis. Intestinal microbiota-derived metabolites also affect fibrosis, including via immune cell regulation to indirectly reduce collagen deposition and direct action on extracellular matrix-related proteins to relieve intestinal fibrosis. The interaction among the AhR, microbiota, and diet suggests new therapeutic strategies, such as dietary interventions and fecal microbiota transplantation, to restore the microbial balance and inhibit fibrosis. The promotion of intestinal fibrosis by AhR agonists in environmental pollutants further emphasizes the need to reduce exposure to environmental toxins while following a plant-based diet rich in AhR agonists.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.461
Threshold uncertainty score0.540

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0010.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.085
GPT teacher head0.453
Teacher spread0.369 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations3
Published2025
Admission routes1
Has abstractyes

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