# Diet and the colonic exfoliome: a novel, non-invasive approach to testing interventions in humans

> **NIH NIH R21** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2020 · $136,323

## Abstract

PROJECT SUMMARY
 Diet is an important risk factor for colorectal cancer (CRC) and several dietary constituents implicated in
CRC are modified by gut microbial metabolism. Microbial fermentation of dietary fiber produces short chain
fatty acids, e.g., acetate, propionate, and butyrate. Dietary fiber has been shown to reduce colon tumors in
animal models and, in vitro, butyrate influences cellular pathways important to cancer risk. Further, work from
our group suggests that the combined effects of butyrate and omega-3 polyunsaturated fatty acids (n-3 PUFA)
may enhance the chemopreventive potential of these dietary constituents. We postulate that the relatively low
intakes of n-3 PUFA and fiber in Western populations and the failure to address interactions between these
dietary components may explain why chemoprotective effects of n-3 PUFA and fermentable fibers have not
been detected consistently in prospective cohort studies. We hypothesize that the combined effects of long-
chain n-3 PUFA supplementation and supplemental highly fermentable fiber will alter critical pathways
important to CRC prevention, particularly intrinsic mitochondrial-mediated programmed cell death resulting
from the accumulation of lipid reactive oxygen species (ferroptosis), cell proliferation, and the
eicosanoid/inflammation pathways.
 We propose a randomized, controlled crossover pilot study in 30 healthy men and women (50-75 y) to
compare supplemental soluble fiber (35 g/d) + supplemental n-3 PUFA (6 g/d EPA+DHA), in quantities
mirroring mean daily intakes associated with lower CRC risk, with a maltodextrin and corn oil control. Stool
samples will be collected at the beginning, middle (day 15), and end of each of the two 30-day intervention
periods. Using a novel, cost-effective, non-invasive approach, we will evaluate differences in global gene
expression signatures in the stool exfoliome (i.e., sloughed colonic epithelial cells in stool) using RNA-Seq.
We will focus on pathways related to colonic cell proliferation and apoptosis/ferroptosis, cell phenotype, and
inflammatory response. Further, we will evaluate changes in gut microbial functional genes involved in butyrate
production using droplet digital PCR (ddPCR). The collection of multiple samples over the intervention periods
will provide a critical measure of longitudinal changes in response to the supplemental n-3 PUFA and
fermentable fiber.
 This proposed pilot human mechanistic study will be the first in humans to integrate and characterize the
relationships between n-3 PUFA and fermentable fiber exposure that modulate programmed cell death and
other CRC-related cell-signaling pathways through metabolic activities of the gut microbiome. Results of this
controlled intervention will help to translate the current mechanistic knowledge from preclinical animal models
to humans and to de-risk and inform approaches for CRC prevention. Interrogating the stool exfoliome is a
novel, cost-effective, non-invasive approach ...

## Key facts

- **NIH application ID:** 9877629
- **Project number:** 1R21CA245456-01
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** Robert Stephen Chapkin
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $136,323
- **Award type:** 1
- **Project period:** 2020-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9877629

## Citation

> US National Institutes of Health, RePORTER application 9877629, Diet and the colonic exfoliome: a novel, non-invasive approach to testing interventions in humans (1R21CA245456-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9877629. Licensed CC0.

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