# Core 2: Microbiome and Therapeutic Probiotics

> **NIH NIH P01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $232,614

## Abstract

CORE 2 SUMMARY/ABSTRACT
The ability to translate pre-clinical findings into viable therapeutic options in humans is a significant
challenge. Recent work investigating the human microbiome has demonstrated that microbial
communities that exist within and upon our bodies play a large role in health and disease. The
microbiota that is harbored in the intestinal tract, due in large part to the vast number and diversity of
microbes in the gut, plays the most crucial role in human health. Therefore, there has been a recent
push to develop microbial-based therapeutics for the treatment of intestinal disease. The main function
of the Therapeutic Probiotic Optimization Core is to provide Projects 1 and 2 with microbial-based
therapeutics that will ameliorate intestinal GVHD. Objective 1 of the core is to isolate novel intestinal
bacteria capable of producing high levels of butyrate and that also possess anti-inflammatory
properties. We have developed human fecal bioreactors that allow for the generation of complex
microbial communities and moderate throughput testing of bacteria that produce butyrate. Core 2 will
provide Project 1 with complex communities that produce high levels of butyrate for testing. Objective 2
of the core is to develop probiotic Lactobacillus reuteri into a therapeutic delivery vehicle to provide IL-
22, REG3A and Reg3γ directly to the intestinal tract. Preliminary data demonstrates that L.reuteri can
secrete active IL-22 and REG3A.
Advances in our basic understanding of the microbiome have set the stage for more detailed
characterizations of the functional properties and metagenomic differences between health and
disease. In the context of BMT and GVHD, several studies have characterized broad differences
between the gut microbiota of BMT patients before and during GVHD. These studies demonstrate a
loss of microbial diversity and an increase Enterococci in during GVHD. To further understand the
pathogenesis of GVHD, it is critical to decipher the mechanisms by which specific strains in a
microbiota mediate GVHD.
The lack of consistent, well-characterized microbiotas in GVHD studies represents a major confounding
factor that could differentiate patients at risk for severe GVHD. Over the past five years, the laboratory
of Dr. Faith, the new director of Core 2, has developed high-throughput microbial isolation pipelines,
high-throughput gnotobiotic community screening technologies, and efficient computational algorithms
to identify specific microbial strains that modulate host physiology. With these microbial culture isolation
methods, the Core has access to a biobank of microbial culture collections with over 600 strains
isolated from 14 individuals. We are therefore in a unique position to use the tools and reagents to
understand the influence of diverse microbial communities on intestinal pathogenesis in experimental
GVHD models. Identification of the specific microbial strains that drive or prevent GVHD will enable
mechanistic stu...

## Key facts

- **NIH application ID:** 10006006
- **Project number:** 5P01CA039542-32
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Jeremiah James Faith
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $232,614
- **Award type:** 5
- **Project period:** 1997-09-10 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10006006

## Citation

> US National Institutes of Health, RePORTER application 10006006, Core 2: Microbiome and Therapeutic Probiotics (5P01CA039542-32). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10006006. Licensed CC0.

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