# Engineering a Humanized Gut-Enteric-Axis

> **NIH NIH R21** · NORTHEASTERN UNIVERSITY · 2020 · $235,500

## Abstract

Project Summary
This project is focused on developing a novel in vitro platform for studying the impact of the enteric nervous
system on epithelial phenotype. There is a need for a simplified model of the human gut-enteric axis, as a clear
connection exists between gut and neural health and dysfunction, but the underlying regulatory mechanisms are
not well understood. The enteric nervous system is known to have tremendous impact on gut homeostasis,
especially the potential for inducing an anti-inflammatory response with vagus nerve stimulation. However, due
to the non-specificity of bioelectric vagal targeting and the limitations of probing innervated organs in vivo,
clinically relevant stimulation regimes for the gut have yet to be identified. Human intestinal epithelial cells
express receptors that are specific for enteric neurotransmitters, such as acetylcholine, which may be activated
during electrical stimulation leading to an anti-inflammatory phenotype. Thus, a microphysiological system that
recapitulates key components of the human gut-enteric-axis, including shear flow, oxygen saturation, bioelectric
stimulation, primary human epithelium, and primary human enteric neurons would be a valuable tool for
advancing scientific discovery, healthcare, compound screening, and biomedical research. Current organ-chips
generally utilize specialized equipment and microfabrication techniques for platform development, limiting
dissemination, as well as do not include primary human small intestinal epithelium or enteric neurons. The
approach here describes the development of a laser-fabricated, cut and assembled body-chip for a humanized
gut-enteric axis (hGEA). The team has worked together to establish a prototype hGEA and establish primary
enteric and epithelial cultures, and thus have demonstrated their complimentary teaming ability towards product
development. Two parallel and synergistic aims will be pursued, with platform development in Aim 1 utilizing
laser machining and assembly to fabricate the hGEA with microelectrode array electrophysiology capabilities,
followed by characterization of neural and epithelial responses on chip compared to static transwell controls over
0-14 days, and lastly oxygen and shear flow modeling to recapitulate physiological conditions. Aim 2 will
investigate the impact of electrical stimulation of enteric neurons to modulate a chemically induced inflammatory
phenotype in the primary human epithelium, and characterize especially (but not limited to) nicotinic acetylcholine
receptor proteins, trans epithelial electrical resistance (TEER), enzyme and mucus production, and cytokine
release as markers of epithelial health. Experiments will be benchmarked to conventional Caco-2 models and
static controls. The successful completion of the first ever in-vitro human GEA will accelerate the mechanistic
study of gut disease, including inflammatory disorders, and advance therapeutic target discovery by enabling
analysis on an acc...

## Key facts

- **NIH application ID:** 9816632
- **Project number:** 5R21EB025395-03
- **Recipient organization:** NORTHEASTERN UNIVERSITY
- **Principal Investigator:** Abigail Nelson Koppes
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $235,500
- **Award type:** 5
- **Project period:** 2017-12-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9816632

## Citation

> US National Institutes of Health, RePORTER application 9816632, Engineering a Humanized Gut-Enteric-Axis (5R21EB025395-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9816632. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*