# Akkermansia muciniphila mucolytic and immunomodulatory properties and intestinal GVHD

> **NIH NIH P01** · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · 2024 · $556,981

## Abstract

PROJECT 2: SUMMARY
There’s emerging evidence that the genetic diversity of the mucophylic gut commensal
Akkermansia muciniphila contribute to this microbe’s overall impact on human health. Based on
our collaborative findings that Akkermansia can exacerbate GVHD following HCT, we predict
that the variance in genetic content among Akkermansia species and clades influences its
impact on GVHD either through variances in its mucin degrading capabilities or through the
regulation of intestinal epithelia and associated immune cells. We propose to define how the
genomic variation among Akkermansia species and clades modulate the risk of developing
neutropenic fever and GVDH following hemopoietic cell transplantation (HCT) in humans and
mouse models of disease. We will test the premise that both mucin degradation by Akkermansia
and other commensal bacteria compounded by capsular polysaccharide-mediated
immunostimulation modulate the initiation and/or severity of disease. We will specifically ask: 1)
How does the genetic diversity of Akkkermansia in humans impact the severity of HCT-induced
GVDH; 2) What is the impact of mucin degradation by Akkermansia on the gut ecology and
damage to the GI by other mucolytic bacteria during HCT; 3) Does immune signaling induced by
the Akkermansia capsule modulate susceptibility to GVHD and 4) Does selective depletion of
Akkermansia with bacteriophages decrease the severity of GVHD in mouse models of HCT?

## Key facts

- **NIH application ID:** 10935665
- **Project number:** 1P01HL170046-01A1
- **Recipient organization:** BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
- **Principal Investigator:** Raphael H Valdivia
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $556,981
- **Award type:** 1
- **Project period:** 2024-09-21 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10935665

## Citation

> US National Institutes of Health, RePORTER application 10935665, Akkermansia muciniphila mucolytic and immunomodulatory properties and intestinal GVHD (1P01HL170046-01A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10935665. Licensed CC0.

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