# Human Intestinal Organoids as a Model for Acute GI-ARS

> **NIH AI U01** · BAYLOR COLLEGE OF MEDICINE · 2026 · $560,175

## Abstract

PROJECT SUMMARY
Gastrointestinal acute radiation syndrome (GI-ARS) is a consequence of exposure to high doses of ionizing
radiation and is characterized by extensive damage to the intestinal epithelium that leads to loss of barrier
function, sepsis, and in some cases mortality. Currently there is a critical need to develop new physiologically
relevant human models to study GI-ARS and to evaluate potential medical countermeasures (MCMs). This
project aims to establish human intestinal organoids (HIOs) as a robust in vitro model for GI-ARS using high-
content imaging approaches to assess the therapeutic potential of a microbial based MCM. Optimization of
radiation dosing will be performed using a large cohort of HIOs that allow assessment of sex, age, and intestinal
region on the response to radiation to be interrogated. A library of biomarkers of radiation damage will be
assembled using novel screening approaches that combine multi-omics analysis, bioinformatic pipelines, and
network analysis. Following biomarker identification, Cell Painting, a high content morphological profiling
technique, will be implemented to characterize the cellular response to radiation treatment in a high throughput
manner using a scanning disc confocal microscope and customized analyses package. The generation of
detailed cellular and subcellular phenotypic profiles that associate with radiation will be used to enable rapid,
quantitative assessment of therapeutic efficacy of a microbial based MCM. The MCMs to be tested are
Limosilactobacillus reuteri 6475 (LR6475) organisms as a modality to deliver key growth factors necessary to
promote regeneration and repair of the intestinal epithelium that target the intestinal stem cell. At the completion
of the proposed studies, HIO will be validated as a translatable model for GI-ARS and a novel imaging based
phenotypic screening pipeline for radiation injury and MCM evaluation will be established. This work will
significantly advance efforts in ra

## Key facts

- **NIH application ID:** 11278171
- **Project number:** 1U01AI195485-01
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** SARAH E BLUTT; ROBERT A BRITTON
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** AI
- **Fiscal year:** 2026
- **Award amount:** $560,175
- **Award type:** 1
- **Project period:** 2026-04-15T00:00:00 → 2031-03-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11278171

## Citation

> US National Institutes of Health, RePORTER application 11278171, Human Intestinal Organoids as a Model for Acute GI-ARS (1U01AI195485-01). Retrieved via AI Analytics 2026-07-03 from https://api.ai-analytics.org/grant/nih/11278171. Licensed CC0.

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