# Mechanisms of microbiome-driven cardiac allograft outcomes

> **NIH NIH U01** · UNIVERSITY OF MARYLAND BALTIMORE · 2024 · $386,250

## Abstract

PROJECT SUMMARY
Though the one-year survival rate in cardiac transplantation has reached 90-95%, the mortality rate beyond the
first year has not changed in the last two decades. Immune-mediated damage remains the primary cause of
long-term graft failure. Findings from our and other studies provide the rationale for investigating the gut
microbiome as a determinant of post-transplantation outcomes and as a potential tool to induce immune
modulation to improve long-term graft outcomes. The goal of this study is to determine the mechanisms by
which the gut microbiome impacts allograft outcome. We postulate that the disrupted metabolic activities of the
gut microbiome lead to inflammatory responses and intestinal injury via cell-type specific responses in the
intestinal cells network, which subsequently modulate alloimmunity and ultimately chronic cardiac graft
outcomes. We will take advantage of our clinically-relevant cardiac transplant murine model of chronic rejection
with well-characterized alloresponses, induced by pro- or anti-inflammatory bacteria, to determine the
alterations in the microbial metabolic activities in Aim 1, then to identify local intestinal barrier changes and the
underlying intestinal cell-type specific responses in Aim 2, and finally to characterize systemic alloresponses
and graft survival in Aim 3, in order to obtain a holistic understanding of the precise mechanisms of
microbiome-driven chronic graft outcomes. The proposed work will identify novel and critical microbiome-based
targets for diagnostic application and therapeutic intervention, and discern the complex and bidirectional
dialogue between the microbiome and alloimmunity to promote transplant immunologic quiescence and long-
term cardiac graft survival.

## Key facts

- **NIH application ID:** 10840823
- **Project number:** 5U01AI170050-03
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Jonathan S Bromberg
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $386,250
- **Award type:** 5
- **Project period:** 2022-05-13 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10840823

## Citation

> US National Institutes of Health, RePORTER application 10840823, Mechanisms of microbiome-driven cardiac allograft outcomes (5U01AI170050-03). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10840823. Licensed CC0.

---

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