# Role of Gut Microbiome in Smoking Induced Promotion of Pancreatic Cancer

> **NIH VA I01** · BIRMINGHAM VA MEDICAL CENTER · 2024 · —

## Abstract

Project Summary
Pancreatic cancer (PDAC) is the 3rd most common cause of cancer-related mortality in the US. Our veterans
and military personnel bear significant brunt of this disease. One of the major obstacles in devising effective
treatment strategies against PDAC is the incomplete understanding of its pathogenesis. For instance, smoking
is one of the major life style factors, which affects PDAC incidence and outcomes. However, our understanding
of the mechanism(s) by which smoking affects PDAC development is still rudimentary. Thus, to develop novel
and effective treatment strategies, we need a better understanding of the pathogenesis of PDAC.
Our recent work has demonstrated that gut microbiome modulates adaptive immune response and promotes
PDAC growth and metastases. Interestingly, few studies suggest that cigarette smoking significantly impact gut
microbiome. Whether, this modulation of gut microbiome in any way mediates the pro-tumorigenic effects of
smoking is not known. Intriguingly, our preliminary data in animal models suggest that gut microbiome is critical
for the smoking induced tumor initiation and progression. Furthermore, with respect to the mechanism, our
preliminary data suggest that smoking induced dysbiosis attenuates anti-cancer immune response. The current
study is the next logical step and clinical investigation of the findings generated from the pre-clinical
models. Based on our preliminary studies we have hypothesized that ‘the cigarette smoking alters gut
microbiome, which in turn promotes tumor initiation and progression in a immune dependent fashion.
This hypothesis will be tested through a combination of a clinical, observational, non-interventional study in
humans, and translational studies in Human Gut Microbiome Avatar Mice (AVATAR) generated using the
samples collected from humans. The study will be executed through the following three specific aims:
In Aim 1, to characterize the effect of smoking on gut metagenome and metabolome, stool samples will be
collected from smokers and non-smoker generally healthy volunteers as well as PDAC patients, and analyzed
by shotgun meta-genomics (for gut metagenome) and LC-MS (unbiased-metabolome). This analysis will help
elucidate the specific gut microbial colonies as well as metabolites, which are enriched in the gut of smokers and
might contribute to the increased incidence and worse outcomes of PDAC and other cancers in them. In Aim 2,
to directly evaluate the effect of the smoking induced dysbiosis on PDAC growth and to elucidate the mechanism
of this effect, we will leverage AVATAR model. Stool from healthy volunteers (smokers and non-smokers, in aim
1), will be transplanted into germ free genetically engineered mouse models of PDAC to yield patient specific
AVATAR mice. The tumor initiation and progression in AVATAR mice generated from the stool of smokers
(healthy volunteers/PDAC patients) will be measured, and compared with those generated from stools of non-
smoker...

## Key facts

- **NIH application ID:** 10585886
- **Project number:** 1I01CX002478-01A1
- **Recipient organization:** BIRMINGHAM VA MEDICAL CENTER
- **Principal Investigator:** VIKAS DUDEJA
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2023-10-01 → 2027-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10585886

## Citation

> US National Institutes of Health, RePORTER application 10585886, Role of Gut Microbiome in Smoking Induced Promotion of Pancreatic Cancer (1I01CX002478-01A1). Retrieved via AI Analytics 2026-08-11 from https://api.ai-analytics.org/grant/nih/10585886. Licensed CC0.

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