# Determining how the human gut microbiota modulates colon cancer tumorigenesis

> **NIH NIH F32** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2021 · $70,458

## Abstract

ABSTRACT
 Colorectal cancer (CRC) is the third most common cancer worldwide with nearly 1.4 million
new cases every year, and rates are predicted to double. Emerging clinical, epidemiological and
laboratory research has demonstrated an important role for gut bacteria in CRC development;
however, research in this field is lacking and only a few members of the human gut microbiota have
been investigated. In addition to exacerbating CRC development, microbes impact the development
of effector T cell subsets that influence tumor killing. Colon tumors are often infiltrated by immune
cells and disease outcome is influenced by which immune cells are recruited to tumors and their roles
within the tumor microenvironment. Despite advances in other cancer types, targeted
immunotherapies for colon cancer treatment have been largely unsuccessful. The microbiota could
be a major factor in causing CRC and in unsuccessful immunotherapies. Therefore, I hypothesize
that differences between the gut microbiotas in healthy and CRC patients contribute to CRC
development and severity.
 To test this hypothesis, I will initially determine if the gut microbiota from human CRC patients
has an effect on tumorigenesis in mouse models of CRC by colonizing Germ Free mice with the fecal
microbiotas from CRC patients and matched healthy controls, and inducing CRC using an
established pre-clinical mouse model for CRC. This aim will identify bacteria that modulate CRC by
either exacerbation of tumorigenesis or protection from CRC. I further aim to characterize tumor
infiltrating lymphocytes (TILs) within the tumor microenvironment during CRC models, and test the
potential of immunogenic bacteria to increase targeted anti-tumor activity, or mitigate tolerogenic
responses that hinder anti-tumor cytotoxicity, using both known and undiscovered human-derived
bacteria isolated from this study. These experiments will identify novel mechanisms by which bacteria
interact with TILs during CRC, and could lead to innovative immunotherapies for CRC.
 Lastly, I will test the hypothesis that secretory IgA sculpting, or the selection of commensal
bacteria by IgA recognition, can lead to detrimental consequences by selecting for pro-tumorigenic
bacteria in the colonic mucosa. These experiments will test if IgA sculpting is a mechanism by which
pro-tumorigenic bacteria colonize the host. Together, results from this study will identify previously
unknown bacteria as important during CRC, leading to new biomarkers and diagnostics, illuminating
new strategies for immunotherapy, and gaining novel insight on the dynamic interplay between host
and microbe.

## Key facts

- **NIH application ID:** 10215257
- **Project number:** 5F32CA243501-03
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** ALLISON WEIS
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $70,458
- **Award type:** 5
- **Project period:** 2019-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10215257

## Citation

> US National Institutes of Health, RePORTER application 10215257, Determining how the human gut microbiota modulates colon cancer tumorigenesis (5F32CA243501-03). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10215257. Licensed CC0.

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