# Intestinal microbiome restoration in allogeneic stem cell transplantation

> **NIH NIH R01** · SLOAN-KETTERING INST CAN RESEARCH · 2024 · $442,500

## Abstract

PROJECT SUMMARY
Allogeneic hematopoietic cell transplantation (allo-HCT) is often associated with a clinical complication known
as graft-versus-host disease (GVHD), a major driver of mortality after allo-HCT. Current approaches to the
prophylaxis of GVHD are primarily immunosuppressive therapies that can dampen the intended activity of the
transplanted immune cells against the tumor and cause delayed immune reconstitution. Gastrointestinal (GI)
microbiota, the highest microbial colonization in the body, has long been understood to contribute to the
pathophysiology of GVHD. Indeed, patients undergoing allo-HCT are subject to dramatic immunological and
microbiota perturbations, developing pre-HCT and continuing during transplant; GI microbiome diversity before
and after transplant are independently associated with clinical outcome. When GVHD occurs, the GI tract is
frequently involved, and patients often succumb to GVHD. New approaches to prevent GVHD and other
transplant-related complications are urgently needed. We hypothesize that restoring the health of the intestinal
microbial community early post-HCT is feasible and associated with improved transplant outcomes and immune
reconstitution. In 2 studies of fecal microbiota transplantation (FMT) in allo-HCT, our group reported that an FMT
intervention is a safe way to restore microbiota diversity. However, FMT has batch-to-batch variability depending
on specific donors and carries the risks of transmission of infectious organisms or antibiotic-resistance genes.
Here, we propose an entirely novel approach: a rationally designed oral-ecobiotic capsule that delivers a defined
composition of pure bacterial strains. An oral, defined blend of strains offers advantages of predictable and
reproducible pharmacology and would be immediately scalable to future studies. On this multi-PI proposal, we
will capitalize on samples from an ongoing, investigator-initiated multicenter placebo-controlled phase 1b trial,
led by PI Doris Ponce, which is first-in-human evaluating a clonally-derived multi-strain bacterial consortia for
the prevention and restoration of the GI microbiome (NCT04995653). Our group has shown in a large multicenter
study that early intestinal microbiome dysbiosis occurred universally among centers and had an association with
transplant outcomes. In addition, innovative preclinical models of microbiome dysbiosis serve as the basis for
the translational study and proposed microbiome analyses. Project objectives: Along with PI Marcel van den
Brink, to evaluate the effects of intestinal microbiota restoration in allo-HCT recipients. We will pursue 2 specific
aims that will evaluate the effects of microbiome restoration in the GI microbiome, allo-HCT outcomes, and
immune reconstitution. Expected outcome: Results will provide new mechanistic insights into interactions
between the intestinal microbiome and host immunity. Impact: Findings will inform future research not only for
the reduction of trans...

## Key facts

- **NIH application ID:** 10824345
- **Project number:** 5R01HL164902-02
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Doris Ponce
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $442,500
- **Award type:** 5
- **Project period:** 2023-05-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10824345

## Citation

> US National Institutes of Health, RePORTER application 10824345, Intestinal microbiome restoration in allogeneic stem cell transplantation (5R01HL164902-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10824345. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*