# Project 1: Biomimetic Interactions Between Bacterial Pathogens and the Gastrointestinal Epithelium

> **NIH NIH U19** · STANFORD UNIVERSITY · 2021 · $330,802

## Abstract

PROJECT SUMMARY (Project 1)
Helicobacter pylori and Salmonella enterica serovar Typhi (Typhi) are both strictly human-adapted pathogens
that colonize the stomach and intestine and are major public health threats worldwide that disproportionally affect
populations with lower socioeconomic resources. H. pylori chronically infects over 50% of the world population
and is the main risk factor for peptic ulcers and gastric cancer. About 77% (812,000) of new cases of gastric
cancer were attributable to H. pylori in 2018 (GLOBOCAN). Gastric cancer is the 3rd leading cause of cancer
death worldwide with about 783,000 deaths reported in 2018 (WHO). Typhi infects more than 20 million people
yearly and causes over 500,000 deaths annually from Typhoid fever. Both H. pylori and Salmonella have evolved
molecular adaptations to chronically colonize human mucosal surfaces and evade clearance from host innate
and adaptive immune responses. In addition, both are becoming increasingly difficult to treat because of rising
antibiotic resistance and poor understanding of their persistence mechanisms. We will address these emerging
problems by leveraging novel biomimetic platforms of human-derived gastric and intestinal organoids including
1) a method to reverse the polarity and control the differentiation of three-dimensional epithelial organoids in
suspension to expose the apical surface for infection studies, 2) a method to induce differentiation of intestinal
microfold (M) cells, and 3) an air-liquid interface culture method to preserve the endogenous mucosal immune
system. We will use these platforms to address difficult-to-model problems, including: 1) defining and
manipulating critical niches that enable bacterial colonization of the epithelial surface, 2) elucidating specialized
sites of invasion and intracellular replication in the mucosa, and 3) understanding secondary activation of
immune responses and immune feedback on the epithelium that control bacterial colonization and disease
progression. These studies will lead to the identification of new pathways that could serve as novel targets for
decolonization, therapeutics, and vaccine strategies.

## Key facts

- **NIH application ID:** 10191937
- **Project number:** 2U19AI116484-06
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** MANUEL R AMIEVA
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $330,802
- **Award type:** 2
- **Project period:** 2015-03-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10191937

## Citation

> US National Institutes of Health, RePORTER application 10191937, Project 1: Biomimetic Interactions Between Bacterial Pathogens and the Gastrointestinal Epithelium (2U19AI116484-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10191937. Licensed CC0.

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