# Non-invasive Monitoring for Infections and Rejection after Lung Transplantation

> **NIH NIH R01** · STANFORD UNIVERSITY · 2024 · $583,817

## Abstract

Project Summary
 Over 4,000 patients receive life-saving lung transplants every year. Unfortunately, chronic respiratory
infection frequently complicates these cases and undermines the long-term benefits of this procedure. However,
it can be difficult to identify infections early or to distinguish them from rejection. Unfortunately, the current
diagnostic gold standard, bronchoalveolar lavage (BAL) fluid culture, is invasive and impractical. We need better,
non-invasive ways to diagnose lung infections.
 One novel but currently insufficient technology that could be developed for this purpose is Next Generation
Sequencing of circulating free DNA (cfDNA). These degraded DNA fragments are released by human cells, and
mirobes into blood plasma. High-throughput sequencing of cfDNA from blood samples is easy, non-invasive,
and has already transformed diagnostics in many areas of medicine.
There is great interest in using microbial cfDNA to diagnose infections. Unfortunately, microbial cfDNA
protocols cannot distinguish between pathogens and closely related organisms that frequently colonize the lungs
of lung transplant recipients. Consequently, microbial cfDNA is not widely used to diagnose infections.
 We have identified a novel approach for identifying microbial pathogens using phages – viral parasites of
bacteria, fungi, and mycobacteria. Because phages are exquisitely specific to their particular host species and
strain, they can provide insights into microbial population dynamics at the strain level. In particular, we find that
when a particular microbial strain causes infection, phages unique to that strain explode in abundance in
peripheral blood. These data suggest that phages can be used to identify their bacterial hosts.
 Further, we find that the circulating phages are a window into the lung. In paired samples of plasma and
bronchoalveolar lavage (BAL) fluid, circulating phages closely mirror the composition of respiratory flora. We
envision that phages in plasma could be used to monitor patients for infections.
It may also be possible to use phages to distinguish between infection and allograft rejection. Donor-derived
cell-free DNA fragments (dd-cfDNA), released by damaged allograft tissues, are a sensitive but not specific
biomarker for rejection. We postulate that phages might add to this specificity by helping to rule out infection.
 Our hypothesis is that circulating phages reflect microbial strain dynamics in the lung and can be used to
identify infections and rejection in lung transplant recipients. To test this, in Aim 1 we will develop protocols for
identifying phages associated with respiratory pathogens and AMR strains. Then, in Aim 2 we will define the
circulating phageome and its relationship to respiratory flora in lung transplant recipients. Finally, in Aim 3 we
will determine whether phages can retrospectively diagnose infections and distinguish these from rejection.
 Together, these bold studies will provide unprecedented i...

## Key facts

- **NIH application ID:** 10990317
- **Project number:** 1R01AI182349-01A1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Paul L Bollyky
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $583,817
- **Award type:** 1
- **Project period:** 2024-06-20 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10990317

## Citation

> US National Institutes of Health, RePORTER application 10990317, Non-invasive Monitoring for Infections and Rejection after Lung Transplantation (1R01AI182349-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10990317. Licensed CC0.

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