# Dissecting Gut Microbiota Modulation on Brain Metastasis Progression

> **NIH NIH F31** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $6,060

## Abstract

Project Summary/Abstract
Brain metastasis is the development of secondary tumors within brain tissue which are typically derived from
melanoma, lung cancer, and breast cancer. The prognosis for patients with brain metastasis is devastatingly
poor with a median survival of less than six months. To reduce brain metastasis incidence and cancer
mortality, rationally-designed therapeutic approaches targeting the mechanistic underpinnings of brain
metastasis progression is imperative.
 It is increasingly appreciated that the immune cells within the brain metastatic niche have indisputable and
ubiquitous roles in regulating brain tumor progression. Yet, the regulation of CNS immunity by peripheral and
systemic factors during brain metastatic colonization and outgrowth are not completely understood. The gut
microbiota composition plays a crucial role in regulating the host’s peripheral immune system, correlates with
anti-cancer immunotherapy efficacy and has a profound influence on brain behavior and function by reshaping
the brain immune niche. In this study, we aim to identify how gut microbiota modulation reshapes the brain’s
immune landscape and subsequently influences the metastatic niche and progression of brain metastasis.
Antibiotic-induced gut microbiota dysbiosis led to a significant increase in brain metastasis burden in contrast
to a vehicle-treated control group, suggesting that gut microbiota dysbiosis remodeled the brain metastatic
niche to a tumor-promoting environment. Using single-cell analysis, we revealed compositional and
transcriptional differences of immune cells within the brain metastatic niche of mice with and without gut
dysbiosis. These findings suggest that gut dysbiosis affects specific immune cell types to promote brain
metastasis outgrowth. Here, we propose to dissect the roles of these immune cell types in promoting brain
metastasis outgrowth under gut dysbiosis conditions. Furthermore, we will elucidate the spatial distribution of
effector immune cells within the brain metastatic niche and functional impact of gut-derived signaling molecules
in brain metastasis outgrowth. Understanding the constituents and host-intrinsic regulators of the brain
metastatic niche shaped through gut-brain communication will guide the development of novel and feasible
brain metastasis prevention strategies through gut microbiota modulation.

## Key facts

- **NIH application ID:** 10912486
- **Project number:** 5F31CA261046-05
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Samantha M Golomb
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $6,060
- **Award type:** 5
- **Project period:** 2021-09-01 → 2024-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10912486

## Citation

> US National Institutes of Health, RePORTER application 10912486, Dissecting Gut Microbiota Modulation on Brain Metastasis Progression (5F31CA261046-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10912486. Licensed CC0.

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