# Bacteriophages as Modulators of Bacterial Colonization

> **NIH NIH K01** · UNIVERSITY OF FLORIDA · 2022 · $105,792

## Abstract

PROJECT SUMMARY
Multidrug-resistant organisms (MDROs) remain major causes of morbidity and mortality in hematopoietic cell
transplant (HCT) recipients. Because of the substantial use of antibiotics in these patients, their gut
microbiome balance is perturbed and becomes dominated by MDROs, vancomycin-resistant enterococci
(VRE) in particular. This disturbance is associated with subsequent invasive infections such as bacteremia that
can lead to fatal outcome. Restoration of the normal balance of the gut flora and reduction or control of MDRO
colonization may curtail these complications and improve outcomes. One innovative approach to restore the
microbiome balance of the gut flora and reduce colonization with MDROs in HCT recipients is the
administration of bacteriophages (i.e., phages). Phages are ubiquitous and natural entities, present in the
environment and in our bodies, and capable of lysing specific pathogens without disturbing the host’s normal
flora while averting the collateral damage of antimicrobial usage. My long-term research goal is to understand
how phages contribute to host-microbe interactions and their overall impact on the health of HCT recipients.
Our preliminary data indicate that VRE colonization can cause inflammation in the gut of germ-free wild-type
mice. Additionally, we found that phages are present in high numbers in HCT patients’ stool samples and that
VRE phages can be recovered from environmental samples and can lyse a variety of VRE strains in a larva
model. The objective of the proposed research is to investigate the interactions between phages, the gut
bacterial microbiome, and host responses in VRE-colonized HCT recipients and to identify biomarkers in the
gut phage population predisposing patients to complications such as bacterial infections or graft versus host
disease. The central hypothesis for this project is that VRE phages can restore balance in the gut microbiota
by reducing inflammation and VRE colonization in HCT recipients. My ultimate goal is to generate significant
findings and new hypotheses for an R01 application aiming at (1) optimizing the design of a chemotherapy-
treated bone marrow-reconstituted mouse model mimicking the condition of HCT patients, (2) testing the
efficacy of phages and phages+antibiotic synergy in preventing major MDRO infections in this mouse model,
and (3) validating the role of certain phage populations in predicting and preventing poor outcomes. The
rationale is that this line of work will provide supportive evidence for future development and evaluation of a
phage-based intervention in humans. My long-term career goal is to become a leading investigator with
expertise in the design of effective and safe phage-based natural therapeutic products that may restore a
healthy gut microbiota and curtail serious complications encountered in HCT recipients (i.e., MDROs), thus
improving their overall health outcomes. The proposal will aid in the fight against MDROs by curtailing ...

## Key facts

- **NIH application ID:** 10350970
- **Project number:** 1K01AI166096-01
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Lynn El Haddad
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $105,792
- **Award type:** 1
- **Project period:** 2021-12-13 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10350970

## Citation

> US National Institutes of Health, RePORTER application 10350970, Bacteriophages as Modulators of Bacterial Colonization (1K01AI166096-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10350970. Licensed CC0.

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