# Genetic analysis of mucin utilization by Akkermansia  muciniphila and its impact on host physiology

> **NIH NIH R01** · DUKE UNIVERSITY · 2021 · $454,955

## Abstract

ABSTRACT
Microbes that inhabit the mucin layer that separates epithelial surfaces from the
bulk of microbial contents of the gastrointestinal tract (GI) play a critical role in
maintaining the metabolic and immunological health of their host. For instance,
the mucolytic, gram negative, obligate anaerobic bacterium Akkermansia
muciniphila is associated with protection from high-fat induced obesity.
Concomitantly, the abundance of this microbe decreases in humans on western
style diets. Importantly, in mouse models of diet-induced obesity, experimental
colonization with A. mucinophila leads to lower rates of weight gain and glucose
resistance. In addition, A. muciniphila contributes to dampening inflammation by
enhancing mucin production and promoting intestinal barrier integrity through
enhanced formation of epithelial cell junctions. Not surprisingly, A. muciniphila is
being considered as a potential commercial probiotic.
Unfortunately, the molecular mechanisms underlying the interactions between
Akkermansia, its host, and associated microbial communities are largely
unknown In this application, we propose to apply genetic methods we recently
developed to characterize the process of mucin acquisition and degradation by
A. mucinipihila, develop new ex vivo colonization models to test the impact of A.
muciniphila exposure on epithelial cell physiology and function, and define the
role that mucin metabolism plays in Akkermansia colonization of mice and its
impact on GI ecology.
The proposed work will generate new genetic tools and host model systems with
which to understand the molecular basis of how this emerging beneficial microbe
exerts its health-promoting effects on its host, and aid in the engineering of A.
muciniphila strains with enhanced probiotic functions.

## Key facts

- **NIH application ID:** 10229490
- **Project number:** 5R01AI142376-04
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Raphael H Valdivia
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $454,955
- **Award type:** 5
- **Project period:** 2018-09-21 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10229490

## Citation

> US National Institutes of Health, RePORTER application 10229490, Genetic analysis of mucin utilization by Akkermansia  muciniphila and its impact on host physiology (5R01AI142376-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10229490. Licensed CC0.

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