Table 1 Summary of studies showing the effect of the microbiome on the AhR/CYP1 pathway and possible mechanisms involved

THP-1 derived macrophages

Fn/kynurenine

↑Kyn (endogenous AhR agonist)

Immune tolerance

IDO activation by LPS-mediated release of TNF-⍺ and IL-6 leads to ↑Kyn

[141]

Administration of ampicillin to B6 pancreatic tumor-bearing mice

Bacterial indoles

↓cyp1a1 mRNA, ↓cyp1b1 mRNA, ↓cyp1a2 mRNA

↑PD-L1, ↑MHCII

↑IFNγ⁺TNFα⁺CD8⁺ T cells

↓Immune tolerance

AhR activation in tumor-associated macrophages by bacterial indoles suppresses CD8⁺ T-cell activity in the tumor microenvironment

[142]

Lyz2^cre/+Ahr^fl/fl B6 pancreatic tumor-bearing mice

TCGA PanCancer Atlas Studies (n = 10,071)

↑AhR with ↓survival

Enrichment of indole-producing bacteria ↓survival

Caco-2 human CRC cells treated with butyrate ± TCDD

Butyrate (SCFA)

↑AhR mRNA, ↑CYP1A1 mRNA, ↑CYP1B1 mRNA

↑TCDD effect

Not measured

Butyrate acts as an HDAC inhibitor, increasing AhR recruitment to the CYP1A1 gene promoter

[143]

HepG2 treated with different SCFAs

SCFAs (butyrate, acetate, and propionate)

↑AhR activity, ↑CYP1A1 mRNA, ↑AhRR mRNA

Not measured

SCFAs act as HDAC inhibitors, increasing AhR recruitment to the cyp1a1 gene promoter

[144]

T18 CRC cells treated with Fn or formate

Fn/formate

↑AhR mRNA

↑ARNT,

↑CYP1A1 mRNA,

↑CSC markers (ALDH, CD44, OCT4, SOX2, CD133, CD24)

↑invasion, ↑metastasis

↑Wnt activation

Fn-derived formate activates AhR and Wnt signaling

[133]