# Elucidating the role of gut, blood, and tumor microbiota in brain metastasis

> **NIH NIH F32** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2021 · $65,994

## Abstract

Project Summary
Brain metastasis is a substantial clinical challenge associated with rising incidence and significant morbidity
and mortality. Understanding the mechanisms underlying the different stages of brain metastasis is essential
for the development of early diagnostic and preventive approaches and efficient therapeutic strategies to
improve the outcome of this disease. The microenvironment in brain metastases is often immune-suppressed,
suggesting a critical role for the immune system in the process of brain metastasis. Our group and others have
demonstrated that gut and tumor microbiota have a major role in shaping the immune system and tumor
immunity in a variety of cancer types. However, the role of microbiota and microbiota-driven immune
modulation in the development and progression of brain metastasis is not clear. Growing evidence
demonstrating a dynamic interaction between gut microbiota and the brain (i.e. gut-brain axis) along with
recent studies showing the presence of intratumoral microbial signatures in primary brain tumors suggest a
prominent role for the microbiota in neoplastic and non-neoplastic diseases of the brain. Consistent with these
findings, our preliminary studies have demonstrated that microbial reads can be detected within sequencing
datasets from metastatic brain tumor tissue. Building on these preliminary findings and the previous studies
from our group and our collaborators, we developed the central hypothesis that distinct gut, blood, and tumor
microbiome signatures can modulate the immune microenvironment in the brain to promote brain metastasis.
In Specific Aim 1, we will identify the gut, blood, and tumor microbiome signatures associated with brain
metastasis in cancer patients. We will analyze the existing whole exome, whole genome, and RNA sequencing
datasets collected from brain metastasis patients and will conduct 16S rRNA gene amplicon and metagenomic
shotgun sequencing to analyze the microbial signatures in prospectively collected fecal, blood, and tumor
samples from brain metastasis patients. We will determine the association between microbial signatures and
the immune profile in cancer patients with and without brain metastasis. In Specific Aim 2, we will conduct
longitudinal studies using preclinical models of microbiome depletion to determine the role of microbiota in
immune modulation and metastasis development during the different stages of brain metastasis. With
microbiota being easily accessible for detection and targetable for modulation, the proposed studies have the
potential to uncover novel aspects of the process of brain metastasis that can be leveraged to develop
diagnostic, preventive, and therapeutic approaches for this disease.

## Key facts

- **NIH application ID:** 10230890
- **Project number:** 1F32CA260769-01
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Golnaz Morad
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $65,994
- **Award type:** 1
- **Project period:** 2021-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10230890

## Citation

> US National Institutes of Health, RePORTER application 10230890, Elucidating the role of gut, blood, and tumor microbiota in brain metastasis (1F32CA260769-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10230890. Licensed CC0.

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