# Mucin preserving strategies to reduce allo HCT toxicities

> **NIH NIH P01** · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · 2024 · $775,660

## Abstract

PROJECT 1 SUMMARY: Mucin-preserving strategies to reduce allo HCT toxicities
 Allogeneic hematopoietic cell transplantation (allo HCT) is a standard therapy for a variety of benign
and malignant hematological diseases. Despite ongoing advances, it remains a high-risk treatment modality,
due in large part to the risk of developing graft-versus-host disease (GVHD), a severe inflammatory condition
that commonly afflicts the intestinal tract and can lead to considerable morbidity and mortality. Work from
multiple groups over the past decade have demonstrated that gut microbiota (GM) injury commonly precedes
GVHD and subsequent treatment-related mortality (TRM).
 The most common source of GM injury in allo HCT patients are antibiotics, which are given to treat life-
threatening infections that commonly arise in these immune-compromised patients. We recently reported
(Hayase, et al, Cell, 2022) that one antibiotic, meropenem, is both associated with increased intestinal GVHD
in allo HCT patients and can aggravate experimental GVHD in mouse models. One major mechanism appears
to be antibiotic-mediated selection of mucus-degrading Bacteroides, which then leads to erosion of colonic
mucus and increased bacterial translocation.
 Neutropenic fever is another common toxicity of all HCT, and we recently published our findings that
Akkermansia and Bacteroides, both of which can degrade mucins, were associated with development of
neutropenic fever (Schwabkey, et al, Sci Transl Med, 2022). Experiments in mice with antibiotic-mediated
depletion of these bacteria, as well as re-introduction of these bacteria, demonstrated that Akkermansia and
Bacteroides species synergize to produce thermodysregulation and compromise intestinal mucus in mouse
models of HCT conditioning.
 In preliminary experiments, have begun to characterize the individual contributions of Akkermansia and
Bacteroides to intestinal GVHD, and have also identified conditions which lead to their expansion and
upregulation of mucus-degrading enzymes. Based on this knowledge, we are developing non-antibiotic
strategies to suppress mucus-degrading behavior by these otherwise usually benign commensal bacteria.
 In this Project, we will further explore the diet-microbiota-mucin axis is a targetable modifier of intestinal
GVHD risk. Our Aims are: 1) To examine how mucus-degrading intestinal bacteria are associated with
intestinal GVHD, and 2) To examine potential efficacy of novel translational strategies to target mucus-
degrading intestinal bacteria in reducing GVHD. Strategies include oral administration of xylose,
propionate, and the naphthoquionone MNQ.

## Key facts

- **NIH application ID:** 10935664
- **Project number:** 1P01HL170046-01A1
- **Recipient organization:** BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
- **Principal Investigator:** Robert Jenq
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $775,660
- **Award type:** 1
- **Project period:** 2024-09-21 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10935664

## Citation

> US National Institutes of Health, RePORTER application 10935664, Mucin preserving strategies to reduce allo HCT toxicities (1P01HL170046-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10935664. Licensed CC0.

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