# Saliva microbiota dynamics and role in metformin-mediated oral squamous cell carcinoma prophylaxis

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $22,862

## Abstract

PROJECT SUMMARY
Oral squamous cell carcinoma (OSCC) claims a quarter of a million lives each year. Epidemiological evidence
has shown that metformin, the most commonly prescribed therapy for type 2 diabetes mellitus, is correlated
with a reduced risk of carcinogenesis. Strong evidence from murine models and in vitro studies suggest that
metformin can also reduce OSCC growth, even in the context of metabolic health. Therefore, a phase II clinical
trial (M4OC- Prevent, NCT02581137) was initiated to test the potential of metformin to reduce the pathology of
oral premalignant lesions (OPL) in non-diabetic patients. Preliminary analysis of this trial has shown that acute
metformin treatment induces a remarkable reduction in pathology. However, the mechanism underlying
metformin’s anti-neoplastic properties remains unknown. Interestingly, over the past year multiple studies
have implicated microbial dysbiosis in cancer onset and therapy. Independently, the anti-diabetic properties of
metformin were shown to be caused by dramatically altering the gut microbiome. Earlier this year, a large
prospective study found significant differences in the oral microbiome that were predictive of future OSCC
development. However, to date no studies have examined the response of the oral microbiome to metformin
treatment. In this proposal, we will test the hypothesis that metformin affects the oral microbiome and that this
effect is related to the anti-neoplastic properties of metformin. Unstimulated saliva samples from patients
enrolled in clinical trial M4OC- Prevent, NCT02581137 were collected before and after metformin treatment,
and the microbiome will be evaluated using novel, quantitative microbial analysis technologies developed in
our lab. Additionally, the diurnal dynamics of the oral microbiome in healthy individuals will be evaluated in
a controlled experiment to determine potential sources of bias in our patient cohort. Lastly, in vitro culturing
and metabolomics experiments taking advantage of genetically modified OSCC cells will allow us to
determine mechanistic background and identify molecules relevant for this relationship. The results from
these experiments will greatly enhance our knowledge of the saliva microbiome and have the potential to
dramatically increase our understanding of human oral health.

## Key facts

- **NIH application ID:** 9836615
- **Project number:** 5F31DE028478-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Clarisse A. Marotz
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $22,862
- **Award type:** 5
- **Project period:** 2019-01-01 → 2020-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9836615

## Citation

> US National Institutes of Health, RePORTER application 9836615, Saliva microbiota dynamics and role in metformin-mediated oral squamous cell carcinoma prophylaxis (5F31DE028478-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9836615. Licensed CC0.

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