# Diet induced modifications of microbiota metabolites in colon tumorigenesis

> **NIH NIH R01** · TEXAS A&M AGRILIFE RESEARCH · 2020 · $99,770

## Abstract

Recent findings suggest that the arylhydrocarbon receptor (AhR) plays a vital role in
the development of colon cancer. While there is evidence that AhR ligands modulate
the intestinal epithelium, the extent to which gut microbiota shape the tumor suppressive
effects associated with exposure to AhR ligands remains an important unresolved
question. We provide novel preliminary data demonstrating that microbiota-derived AhR
ligand levels are decreased under high fat diet (obesogenic) conditions. This is
noteworthy, because a growing body of preclinical and epidemiological data indicate that
the risk of colon cancer is strongly associated with obesity. Since transformation of adult
stem cells is an extremely important route towards initiating intestinal cancer, we
propose to interrogate the effect of microbiota-derived AhR ligands on intestinal stem
cell homeostasis and colon tumorigenesis using tissue-specific AhR knock out and
control compound mice fed high fat versus low fat diets. This objective is supported by
our novel preliminary data indicating that microbial-derived AhR ligands have a direct
effect on the intestinal epithelium (without the contribution of the mesenchymal niche)
and modulate stemness. Based on these findings, we hypothesize that microbial-
derived AhR ligands are important determinants of colonic malignant transformation. To
unravel the intricacies of AhR effects on intestinal biology, the following specific aims will
be addressed: (1) Identify microbiota-derived AhR ligands that are modulated by high-fat
feeding; (2) Determine the effect of microbiota-derived AhR ligands on intestinal stem
cell responses in vivo and ex vivo; and (3) Determine whether microbe-derived AhR
ligands modulate colon cancer initiation and progression. At the completion of this
project, we anticipate that our novel approaches will provide us with a unique snap shot
of host-microbe metabolite interactions during tumorigenesis.

## Key facts

- **NIH application ID:** 9930552
- **Project number:** 5R01CA202697-05
- **Recipient organization:** TEXAS A&M AGRILIFE RESEARCH
- **Principal Investigator:** Clinton D Allred
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $99,770
- **Award type:** 5
- **Project period:** 2016-07-01 → 2020-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9930552

## Citation

> US National Institutes of Health, RePORTER application 9930552, Diet induced modifications of microbiota metabolites in colon tumorigenesis (5R01CA202697-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9930552. Licensed CC0.

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