# Mucus-degrading intestinal bacteria and toxicities of hematopoietic cell transplantation

> **NIH NIH P01** · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · 2024 · $2,594,544

## Abstract

OVERALL PROGRAM SUMMARY: Mucus-degrading intestinal bacteria and toxicities of hematopoietic
cell transplantation
 The microbial community (microbiota) in the human gut plays a central role in digestion of dietary fiber,
providing nutrients to the gut microbiota as well as to the host through fermentation products like short-chain
fatty acids. A minority of gut bacteria can also utilize nutrients derived from mucus, a complex mixture of
secreted, mucin glycoproteins that form a layer over the epithelium to protect it from microbial encroachment.
The most abundant mucin utilizers are members of the genera Akkermansia and Bacteroides.
 Allogeneic hematopoietic cell transplantation (allo HCT) is an important treatment modality performed
for a variety of benign and malignant hematological conditions. Patients receive systemic cytotoxic
conditioning, followed by infusion of allogeneic hematopoietic cells. In two recent manuscripts co-authored by
the Program Project Grant (PPG) Project and Core leaders, mucin-utilizing intestinal bacteria were found to
contribute to intestinal graft-versus-host disease (GVHD) that is aggravated by meropenem antibiotic
treatment, and neutropenic fever (NF).
 This is a revised PPG proposal with 3 integrated projects addressing how mucin-utilizing intestinal
bacteria contribute to intestinal GVHD. Recent preliminary data from experiments performed in mice identified
that Akkermansia and Bacteroides combine to compromise the colonic mucus layer, produce hypothermia in
models of HCT conditioning, and aggravate intestinal GVHD. The Projects of this PPG will extend these
findings, improving our understanding of how diet and metabolism modulate expression of mucin-degrading
enzymes in Akkermansia and Bacteroides.
 Project 1 builds upon expertise in clinical allo HCT microbiome profiling and preclinical modeling to
develop translational approaches. Project 2 incorporates an understanding of the natural landscape of
Akkermansia genetic heterogeneity, coupled with an extensive library of functional Akkermansia mutants to
deeply characterize the role of Akkermansia in intestinal GVHD. Finally, Project 3 offers a comprehensive
analysis of the effects of specific dietary glycans on mucin-degrading Bacteroides and genetic underpinnings
regulating expression of mucin-degrading enzymes.
 Supporting these are 2 unique cores. Core A will provide administrative services, microbiome-
specialized biostatistical support, clinical specimen and data collection from patients undergoing allo HCT at
two centers, and bionutritional support for collection of dietary data supplemented by metagenomic sequencing
of fecal chloroplast DNA. Core B will perform random and targeted bacterial mutagenesis to support high
throughput mutant screens as well as testing specific hypotheses, generate fluorescently labelled glycans to
visualize glycan uptake and degradation at the single cell level, and build a database of mucin-degrading
bacterial enzymes that wil...

## Key facts

- **NIH application ID:** 10935661
- **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:** $2,594,544
- **Award type:** 1
- **Project period:** 2024-09-21 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10935661

## Citation

> US National Institutes of Health, RePORTER application 10935661, Mucus-degrading intestinal bacteria and toxicities of hematopoietic cell transplantation (1P01HL170046-01A1). Retrieved via AI Analytics 2026-06-03 from https://api.ai-analytics.org/grant/nih/10935661. Licensed CC0.

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