# Intestinal Barrier Repair Mechanisms in Giardiasis

> **NIH NIH F31** · GEORGETOWN UNIVERSITY · 2024 · $41,605

## Abstract

PROJECT SUMMARY
Giardia duodenalis (syn G. lamblia, G. intestinalis) is a common protozoan parasite that causes the diarrheal
disease, Giardiasis. This disease is prevalent among individuals in low and middle-income countries (~200
million cases annually). While acute symptoms include diarrhea and vomiting, Giardiasis can also be subclinical.
Long-term consequences of Giardiasis may include irritable bowel syndrome and growth stunting in children.
Studies have suggested that growth stunting occurs due to impaired absorption of nutrients in the small intestine,
and intestinal barrier dysfunction leading to nutrient malabsorption has been linked to infection with Giardia.
However, the mechanisms underlying this phenomenon have yet to be well explored. While most research has
focused on mechanisms whereby infection leads to barrier damage, it is essential to also understand the repair
dynamics between bouts of active infection. This proposal examines how intestinal barrier repair signaling occurs
after Giardia-induced barrier damage. I will use an established mouse malnutrition model to investigate possible
mechanisms of barrier repair post-infection with Giardia. The overarching hypothesis of this proposal is that
Giardia alters the production of metabolites by the gut microbiome leading to defective repair of the damaged
intestinal barrier. Previous research has found that metabolites of the amino acid tryptophan can mediate
intestinal barrier repair by activating the Aryl hydrocarbon receptor (AHR). Analysis of urinary metabolites in
Giardia-infected children indicated reduced levels of tryptophan (Trp), along with other amino acids. Also,
unpublished analyses of blood plasma metabolites in children and mice infected with Giardia yielded similar
results, leading to my hypothesis of defective barrier repair in Giardiasis. To address this hypothesis and carry
out the objectives of this proposal, I will quantify specific microbiota produced Trp metabolites in the plasma of
infected mice by mass spectrometry. Additionally, I will analyze epithelial barrier damage and repair with various
assays. To further understand the importance of AHR ligands, I will supplement the diets of infected mice with
either Trp or Trp metabolites and examine weight gain, epithelial permeability, and repair dynamics. Specific
assays include immunostaining for Ki67 to quantify proliferating IECs, qPCR to measure levels of IL-22 mRNA,
and western blotting of villin and ezrin to determine protein levels and identify post-translational modifications
related to barrier repair. Broad-spectrum antibiotics will be used to determine the role of the microbiota in
converting Trp to metabolites that can activate AHR. Finally, I will utilize Ahr-deficient mouse models to identify
the involvement of AHR more precisely in facilitating barrier repair in Giardiasis. Completing this project will
significantly improve our knowledge of barrier repair in Giardia-infected individuals and help u...

## Key facts

- **NIH application ID:** 10903020
- **Project number:** 1F31AI183732-01
- **Recipient organization:** GEORGETOWN UNIVERSITY
- **Principal Investigator:** Rita Taye Kosile
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $41,605
- **Award type:** 1
- **Project period:** 2024-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10903020

## Citation

> US National Institutes of Health, RePORTER application 10903020, Intestinal Barrier Repair Mechanisms in Giardiasis (1F31AI183732-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10903020. Licensed CC0.

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