# The impact of Giardia metabolism in causing gastrointestinal dybiosis

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $196,250

## Abstract

Giardia lamblia is microaerophilic protozoan parasite of humans and animals that causes significant diarrheal
disease worldwide. Ingested cysts transform into motile trophozoites as they pass into the gastrointestinal
tract. As microaerophiles, non-encysting trophozoites have a fermentative metabolism with unique end
products. Encysting trophozoites have a dramatically different metabolism, defined by metabolic shifts from
glycolysis to the GlcNAc pathway, arginine fermentation by the ADiHP pathway, and upregulation of lipid
biosynthesis during the production of the cyst wall. Giardia produces no known toxin, and colonization does not
elicit a robust inflammatory reaction. Giardia colonization of the small intestine occurs in a niche already
inhabited by commensal microbiota, yet in vivo Giardia-microbiome interactions have largely been ignored in
models of pathogenesis. We recently showed that Giardia infection of mice results in a dysbiosis at the primary
site of colonization in the small intestine and other dysbioses extend to other regions of the gut. Using
bioluminescent imaging (BLI) methods developed in our lab, we discovered that trophozoites rapidly encyst in
foci of infection within days of inoculation, primarily in the small intestine. Using BLI-mediated precise sampling
of these encysting foci, we demonstrated that encysting trophozoites have a unique in vivo transcriptional
signature defined by significant upregulation of encystation and redox-response. We thus hypothesize that
encysting trophozoites have a specific and differential impact on small intestine dysbiosis as
compared to non-encysting trophozoites. This proposed work evaluates and quantifies the effect of
encysting and non-encysting trophozoite metabolic activity on host microbiome metabolic activity. In
Aim 1, we compare the differential impacts of encysting and non-encysting Giardia trophozoites on the small
intestinal microbiome metabolism and on known host immune responses. We will infect animals with a dual-
tagged (constitutive and encystation-specific) reporter strain to facilitate non-invasive in vivo quantification of
encysting and non-encysting trophozoites during the course of infection. We define microbiome community
structure and metabolism using total community metagenomic and metabolomic analyses and key immune
responses using BLI-mediated precision ex vivo sampling of sites with encysting and non-encysting
trophozoites. In Aim 2, we further explore the metabolic interactions between encysting or non-encysting
trophozoites and the microbiome by infecting animals with a dual-reporter encystation-defective CWP1 null
mutant that is unable to generate viable cysts. Defining exactly how the microbiome is affected in Giardia
infections is a first and necessary step toward designing microbiome-mediated therapies. Our detailed
analyses of Giardia-microbiome interactions provide a foundation for future studies of the impacts of
colonizing Giardia trophozoites (encys...

## Key facts

- **NIH application ID:** 9849176
- **Project number:** 5R21AI138150-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Scott C Dawson
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $196,250
- **Award type:** 5
- **Project period:** 2019-01-11 → 2020-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9849176

## Citation

> US National Institutes of Health, RePORTER application 9849176, The impact of Giardia metabolism in causing gastrointestinal dybiosis (5R21AI138150-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9849176. Licensed CC0.

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