# Gut microbiota-related mechanisms that impact colorectal cancer risk after bariatric surgery

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $688,648

## Abstract

Abstract: Bariatric surgery, currently the most effective treatment for morbid obesity, has become increasingly
common in the US. Besides substantial and sustained weight loss, bariatric surgery leads to dramatic changes
in many aspects of human physiology, including glycemic control, bile acid metabolism, immunosurveillance,
and gut microbiota. These changes, if sustained after surgery, may affect the risk of colorectal cancer (CRC).
On one hand, reduced obesity, insulin resistance, and systemic inflammation may lower CRC risk; meanwhile,
increased exposures to some bile acids (e.g., ursodeoxycholic acid) and beneficial bacteria (e.g., Akkermansia
muciniphila & Faecalibacterium prausnitzii) may also lower CRC risk. On the other hand, increased exposures
to other bile acids (e.g., deoxycholic acid) and bacteria (e.g., aerotolerant species) may increase CRC risk after
bariatric surgery. While the interplays of gut microbiota with host metabolism & immunity have been implicated
in CRC etiology, it is unclear what sustained changes in gut microbiota are induced by bariatric surgery
and how post-surgery “gut microbiota-host interactions” may impact CRC risk. Longitudinal studies with
repeated collections of biospecimens (e.g., blood & stool) and patient data (e.g., diet & medication) are needed
to tackle these questions but currently lacking. ●Building on a longitudinal cohort of bariatric surgery patients,
we propose to investigate, in Aim 1 (targeted evaluation): pre- to 1-year and 3-years post-surgery changes in
potential CRC-related bacteria (e.g., Fusobacterium nucleatum, enterotoxigenic B. fragilis, & pks+ E. coli),
major microbial metabolites (e.g., bile acids & short-chain fatty acids), and established markers of systemic
and microbial inflammation (e.g., C-reactive protein & LPS-binding protein); in Aim 2 (omics-wide discovery):
the most significantly and consistently altered bacteria, microbial metabolites, and inflammatory & immune
response proteins at 1- and 3-years post- vs. pre-surgery, using shotgun metagenomics, global metabolomics,
and proteomics; in Aim 3 (in vivo experiments): the causality and molecular mechanisms of post- vs. pre-
surgery gut microbiota in CRC carcinogenesis. We will perform fecal microbiota transplant (FMT) on antibiotic-
treated, genetic mouse models of CRC using preserved pre- and 3-years post-surgery stools and compare
adenoma/tumor burden, colonocyte biology, and systemic & intestinal inflammation between those groups and
with mice receiving a group of bacteria with the largest and consistent post-surgery increases as identified in
Aim 2 and with control. ●Leveraging a longitudinal cohort of bariatric surgery patients and applying state-of-
the-art multi-omics and FMT in pre-clinical models, our study will fill research gaps regarding sustained post-
bariatric surgery changes in gut microbiota and microbial molecules and how they contribute to patients'
metabolic, inflammatory, and immunological profiles, an...

## Key facts

- **NIH application ID:** 10923948
- **Project number:** 5R01CA275864-02
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** CHARLES R FLYNN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $688,648
- **Award type:** 5
- **Project period:** 2023-09-07 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10923948

## Citation

> US National Institutes of Health, RePORTER application 10923948, Gut microbiota-related mechanisms that impact colorectal cancer risk after bariatric surgery (5R01CA275864-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10923948. Licensed CC0.

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