# Host and Microbial Metabolism in Graft versus Host Disease

> **NIH NIH P01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $2,295,629

## Abstract

PROJECT SUMMARY/ABSTRACT
The program project grant’s (PPG’s) overarching goal is to make allogeneic hematopoietic cell
transplantation (allo-HCT) safer and more efficacious for patients with non-malignant and malignant blood
diseases. Towards this end, it will address importance of microbiome in mitigating the severity of graft-
versus-host disease (GVHD), the most significant complication of allo-HCT and improving outcomes after
allo-HCT. The proposal has a unifying central theme, specifically to understand the role of intestinal
microbial metabolite interactions with host metabolism and impact on intestinal GVHD. The proposed
projects in the PPG are independent and yet synergistic. It will integrate big data (cutting edge
technologies high throughput sequencing of genomes of microbial communities complemented by
metabolomes), mechanistic studies of fundamental microbial and mammalian biology in well-defined
HCT model systems and in humans, and, also importantly an IRB approved bench to bedside translation
of these into proof of concept prospective human clinical trial under an IND from FDA. The PPG brings
together investigators who are leaders from diverse fields into a cohesive group that has worked,
published together and bring their varied expertise to improve outcomes of allo-HCT for blood diseases.
The PPG being proposed will have four projects and four cores. All projects germinated from the common
unified preliminary datasets that were generated by project leaders over last several years. Project 1 will
explore the role of crosstalk between host intestinal epithelial cell (IEC) mitochondria and microbial
metabolites, specifically the short chain fatty acid (butyrate) in murine models of GVHD. In synergistic,
yet distinct line if investigation, project 2 will explore the role of host-microbiome interaction dependent
metabolites, secondary bile acids (SBAs), on IEC homeostasis and GVHD in murine models. Project 3
will delineate the critical microbes and the mechanisms employed by them in breaking down specific host
diet (resistant starch) to generate butyrate and SBAs. The role of dietary resistant starch on host
microbiome and metabolome and its impact on clinical GVHD will be explored in a proof of concept
clinical trial in project 4. These projects will be facilitated by state of the art Cores that include
Metabolomics, Gnotobiotics mice and bacterial phenotyping, Bioinformatics, Biostatistics and supported
by the Administrative Core. All of the investigators are from University of Michigan (a single institution).

## Key facts

- **NIH application ID:** 10241900
- **Project number:** 5P01HL149633-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** PAVAN REDDY
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,295,629
- **Award type:** 5
- **Project period:** 2020-09-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241900

## Citation

> US National Institutes of Health, RePORTER application 10241900, Host and Microbial Metabolism in Graft versus Host Disease (5P01HL149633-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10241900. Licensed CC0.

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