# Colorectal carcinogenesis and Fusobacterium nucleatum: oncomicrobe, oncometabolites, and oncoimmunology

> **NIH NIH R01** · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · 2022 · $378,813

## Abstract

PROJECT SUMMARY
Configurations of the gut microbiome and specific bacterial species are associated with CRC, and such data
provide fresh perspectives and insights into CRC susceptibility, response to therapy, and therapeutics. A central
challenge of cancer gut microbiome studies is to define the bioactive features of micro-organisms that influence
CRC susceptibility and progression. Fusobacterium nucleatum, a Gram-negative anaerobic bacterium, is a
normal constituent of the human oral microbiome. However, numerous studies now demonstrate that F.
nucleatum (Fn) is enriched in human colorectal adenomas and CRC compared to healthy colonic tissues, as
well as in stool from individuals with CRC, and that tumoral Fn-enrichment correlates with worse overall-survival,
progress-free survival and chemoresistance. My lab has been involved in studies detecting Fn in adenomas and
CRC, correlating fusobacterial presence with various CRC risk factors, and determining how Fn may contribute
to CRC using preclinical CRC models with a focus on its interactions with immune cells. Yet, much remains to
discover about the mechanisms by which Fn contributes to CRC. To date, the bulk of studies on Fn virulence
mechanisms in CRC have focused on its adhesins and its lipid polysaccharide. While such studies have revealed
important biology about Fn, there are additional mechanisms that may underlie Fn's contribution to CRC. In this
renewal proposal, we build upon our expertise with Fn, microbial metabolism, and immunology to further
understanding of how Fn contributes to CRC. Specifically, we will investigate the effects of three bioactivities, Fn
hydrogen sulfide production, short-chain fatty acids and Fic proteins, on the colonic epithelium and immune cells
in the evolving tumor microenvironment. In considering broader mechanisms used by but not exclusive to Fn,
we hope to extend the applicability of our findings to Fn-negative CRC and other malignancies.

## Key facts

- **NIH application ID:** 10520591
- **Project number:** 2R01CA154426-11
- **Recipient organization:** HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH
- **Principal Investigator:** Wendy S. Garrett
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $378,813
- **Award type:** 2
- **Project period:** 2011-03-18 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10520591

## Citation

> US National Institutes of Health, RePORTER application 10520591, Colorectal carcinogenesis and Fusobacterium nucleatum: oncomicrobe, oncometabolites, and oncoimmunology (2R01CA154426-11). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10520591. Licensed CC0.

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