# Prevention of Brain Metastasis Relapse through Modulation of Age-related Gut Microbiota-Immune Cross talk

> **NIH NIH R21** · UNIVERSITY OF NOTRE DAME · 2021 · $219,491

## Abstract

Project Summary
 Metastasis is the major cause of cancer mortality, with brain metastasis being the most aggressive and
incurable form of metastatic recurrence. The prognosis for breast cancer patients with brain metastasis is
devastatingly poor with a median survival of less than six months. Brain metastasis relapse depends on the
intricate interplay between disseminated tumor cells and components of the brain metastatic microenvironment
- the niche. To combat breast cancer mortality, it is imperative to develop rationally-designed strategies to
prevent brain metastasis relapse.
 The immune system plays a significant role in regulating both primary and metastatic tumors. The gut
microbiota - an ecological community of commensal, symbiotic, and pathogenic microorganisms consistently
primes and reshapes the immune surveillance system during aging. Mounting evidence in the neuroscience
field demonstrated a clear connection between gut microbiota dysbiosis and brain inflammation as well as
various neurological diseases. As brain metastasis relapse often occurs in aged breast cancer survivors, in this
proposed study, we will focus on delineating mechanisms by which the microbiota-host immune interaction
influences metastatic progression in the aged female population. We postulate that age-related gut dysbiosis
may reshape the brain immune metastatic niche to influence brain metastatic relapse. Our overarching goal
is to dissect the mechanistic connection between gut dysbiosis and brain metastasis relapse and identify
clinically actionable probiotics modulation strategies tailored to aged breast cancer survivors to prevent brain
metastatic relapse. Based on well-established aging models, cutting-edge single-cell genomics, and
metagenomics approaches, we will examine molecular changes in brain metastatic tumors with gut microbiota
alterations in the aged host. Then design and test targeted microbiota-modulation strategies to prevent brain
metastatic relapse in aged hosts.
 This project is the first attempt to explore the mechanistic link between the gut microbiota and breast
cancer brain metastatic niche in the aging context. From the cancer prevention perspective, mechanistic
insights via examining age-associated dysbiosis in regulating brain metastasis relapse will guide personalized
microbiota-modulation strategy that is tailored to each breast cancer survivor to prevent deadly brain
metastatic relapse.

## Key facts

- **NIH application ID:** 10287850
- **Project number:** 1R21CA263798-01
- **Recipient organization:** UNIVERSITY OF NOTRE DAME
- **Principal Investigator:** Siyuan Zhang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $219,491
- **Award type:** 1
- **Project period:** 2021-08-03 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10287850

## Citation

> US National Institutes of Health, RePORTER application 10287850, Prevention of Brain Metastasis Relapse through Modulation of Age-related Gut Microbiota-Immune Cross talk (1R21CA263798-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10287850. Licensed CC0.

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