# Microbiota mechanisms and biomarkers in GVHD

> **NIH NIH K08** · SLOAN-KETTERING INST CAN RESEARCH · 2021 · $171,612

## Abstract

Project Summary
 Allogeneic hematopoietic-cell transplantation (allo-HCT) is an important treatment for hematological
malignancies. The intestinal microbiota consists of a community of diverse microbes that reside in the intestine
and are critical for host development, homeostasis, and immune regulation. In human analyses and animal
experiments, we and others have shown that the intestinal microbiota contribute to the pathophysiology of all
three major complications of allo-HCT: infections, GVHD, and relapse. Using 16S ribosomal RNA next-
generation sequencing, we examined the intestinal microbiota of allo-HCT patients and found a post-transplant
“microbiota injury”. This dysbiosis is likely due to the combined effects of (a) broad-spectrum antibiotics for the
treatment of post-transplant febrile neutropenia and (b) the profound nutritional alterations experienced by
these patients. We found an inverse relationship between a loss of the genus Blautia after allo-HCT and GVHD
mortality. We observed that broad-spectrum antibiotics that target the anaerobic commensal flora are
particularly associated with increases in GVHD-related mortality and in fact worsened intestinal GVHD in our
animal model. We and others have observed an association between Enterococcus and the development of
GVHD in mouse and man. Finally, we have found an association between Eubacterium limosum and graft-vs-
tumor activity after allo-HCT. Therefore, we hypothesize that the intestinal microbiota can modulate
alloreactivity. We propose in Aim 1 to identify microbiota biomarkers of GVHD in allo-HCT patients and to
develop a clinically useful multi-parameter, rapid-turnaround biomarker panel. In Aim 2, we will use mouse
models to study the mechanisms by which members of the microbiota affect alloreactivity, including both
GVHD and graft-vs-tumor activity. In addition to elucidating the interactions of the intestinal microbiota in the
development of GVHD, this work will form the basis of clinical trials to reduce GVHD and transplant-related
mortality.
 During the award period, the candidate will conduct research at Memorial Sloan Kettering Cancer
Center under the mentorship of Dr. Marcel van den Brink and an Advisory Committee. He will obtain the critical
skills he needs to become a tenure-track physician-scientist who runs his own academic laboratory and
competes for independent NIH funding. He will acquire detailed and comprehensive knowledge of mouse
microbiota models, statistical methods in biomarker development, and computational-biology approaches to
the analysis of high-dimensional microbiome sequencing data.

## Key facts

- **NIH application ID:** 10111552
- **Project number:** 5K08HL143189-03
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Jonathan Peled
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $171,612
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10111552

## Citation

> US National Institutes of Health, RePORTER application 10111552, Microbiota mechanisms and biomarkers in GVHD (5K08HL143189-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10111552. Licensed CC0.

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