# Center for High-Throughput Minimally-Invasive Radiation Biodosimetry

> **NIH NIH U19** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2022 · $171,000

## Abstract

ABSTRACT (30 line limit):
 Multi-organ radiation-induced injury represents a significant unmet medical need that occurs during
accidental exposure, radio-cancer therapy or a targeted terror attack. Substantial federal efforts have been made
to mitigate acute radiation symptoms; however, it remains a long-standing and unresolved problem. Intestinal
epithelium is the fastest-renewing adult tissue, making it highly sensitive to radiation and thereby the major
target of acute injury during environmental overexposure and radiation therapy. The gastrointestinal (GI) tract
harbors a complex microbial community that comprises 10-100 trillion microorganisms. The microbiota has
known roles in multiple diseases, such as inflammatory bowel disease (IBD), type 2 diabetes, intestinal vascular
remodeling and neuronal homeostasis. Recently, there is increasing evidence linking the intestinal microbiota
to radiation induced syndromes.
 We have shown that GI microbiota composition can affect the outcome of high dose total body irradiation
(TBI) (Science 2020). We described an unexpected finding that a small percentage of animals can survive lethal
TBI and live a normal life span. These elite-survivors harbor a distinct gut microbiota which are protective
against radiation. A detailed delineation has narrowed down the bacteria that are beneficial for TBI.
Lachnospiraceae plays a vital role in enhancing hematopoietic stem cell regeneration and gastrointestinal
epithelial repair post radiation. We further identified propionate, a short chain fatty acid (SCFA) and the key
metabolite that acts downstream from Lachnospiraceae, to serve as a potent radio-protectant. More strikingly,
tryptophan pathway metabolites (1H-indole-3-carboxaldehyde and kynurenic acid) are also selectively found
in the elite-survivors and provide radioprotection. Although we have uncovered the correlation between gut
microbiota/metabolites and radiation-induced damage, and the use of these metabolites to mitigate radiation
damage, the detailed underpinnings of the mechanism remain under investigation.
 This proposal aims at elucidating the mechanism of how the microbiota derived metabolites ameliorate
radiation injury. We will focus on identifying which cell types and metabolites receptors play the essential role
in mediating the radioprotection by SCFA or tryptophan metabolites and confirming whether this function is
controlled by the gut microbiota in the radiation model. This work would provide insight into both disease
pathophysiology and potential therapeutics, leading to better and more efficient treatments against radiation
injury in the cases of radiation exposure after a radiological/nuclear terrorist event, accidental exposure, and
radio-cancer therapy.

## Key facts

- **NIH application ID:** 10590249
- **Project number:** 3U19AI067773-17S2
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** DAVID JONATHAN BRENNER
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $171,000
- **Award type:** 3
- **Project period:** 2022-05-26 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10590249

## Citation

> US National Institutes of Health, RePORTER application 10590249, Center for High-Throughput Minimally-Invasive Radiation Biodosimetry (3U19AI067773-17S2). Retrieved via AI Analytics 2026-06-16 from https://api.ai-analytics.org/grant/nih/10590249. Licensed CC0.

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