The Innervation of Human Gut Sensory Epithelial Cells
| Status: | Recruiting |
|---|---|
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 12/13/2018 |
| Start Date: | September 5, 2017 |
| End Date: | October 2020 |
| Contact: | Diego Bohorquez |
| Email: | diego.bohorquez@duke.edu |
| Phone: | 919-684-4520 |
The study has two objectives:
1. To obtain endoscopic and colonoscopic biopsies to harvest and culture intestinal crypts
from human tissue to produce organoids. These organoids will be used to study the
biology of innervated sensory epithelial cells.
2. to collect subject data relating to clinical management and demographic characteristics
of patients undergoing upper endoscopy or colonoscopy to learn the mechanisms behind
visceral hypersensitivity, and neurodegenerative diseases that may arise in the gut.
1. To obtain endoscopic and colonoscopic biopsies to harvest and culture intestinal crypts
from human tissue to produce organoids. These organoids will be used to study the
biology of innervated sensory epithelial cells.
2. to collect subject data relating to clinical management and demographic characteristics
of patients undergoing upper endoscopy or colonoscopy to learn the mechanisms behind
visceral hypersensitivity, and neurodegenerative diseases that may arise in the gut.
Throughout the gastrointestinal tract there are specialized sensory epithelial cells that
recognize stimuli from nutrients and bacteria. These cells have been traditionally known for
their endocrine function. However, it was recently discovered using mouse models that these
cells receive synaptic inputs from enteric and peripheral neurons, such as those with cell
bodies in dorsal root ganglia or the vagal nodose.
This finding opened a few possibilities, including the following: 1) sensory function of the
gastrointestinal tract is modulated by neural activity; 2) gut bacteria influences brain
function through a direct neural circuit; and 3) viruses that preferentially infect neurons
access the central nervous system through this neural circuit [1,2]. To translate findings in
animal models to humans, the investigator must test the hypotheses in which the physiology of
gut sensory epithelial cells resembles that of humans.
Visceral hypersensitivity is a core symptom for several gastrointestinal and brain behavior
disorders, including irritable bowel syndrome, autism and anorexia. Unfortunately, the basic
mechanisms of sensory processing in the wall of the gut are non-existent. This lack of
knowledge precludes the development of therapeutic strategies to treat disorders linked to
visceral hypersensitivity. The investigator's efforts to translate animal research into human
models will be a foundation to develop target therapies for visceral hypersensitivity.
Today, it is possible to derive organoids from intestinal crypts harvested from human
intestinal or colonic tissue. The organoids have all epithelial cell types, including gut
sensory cells. Here, the investigator's goal is to use de-identified human tissues to culture
intestinal organoids in the laboratory, and use it as a platform to study the biology of
innervated sensory epithelial cells. This work is significant because it will open the
possibility to learn the mechanisms behind visceral sensation and neurodegenerative diseases
that may arise in the gut.
recognize stimuli from nutrients and bacteria. These cells have been traditionally known for
their endocrine function. However, it was recently discovered using mouse models that these
cells receive synaptic inputs from enteric and peripheral neurons, such as those with cell
bodies in dorsal root ganglia or the vagal nodose.
This finding opened a few possibilities, including the following: 1) sensory function of the
gastrointestinal tract is modulated by neural activity; 2) gut bacteria influences brain
function through a direct neural circuit; and 3) viruses that preferentially infect neurons
access the central nervous system through this neural circuit [1,2]. To translate findings in
animal models to humans, the investigator must test the hypotheses in which the physiology of
gut sensory epithelial cells resembles that of humans.
Visceral hypersensitivity is a core symptom for several gastrointestinal and brain behavior
disorders, including irritable bowel syndrome, autism and anorexia. Unfortunately, the basic
mechanisms of sensory processing in the wall of the gut are non-existent. This lack of
knowledge precludes the development of therapeutic strategies to treat disorders linked to
visceral hypersensitivity. The investigator's efforts to translate animal research into human
models will be a foundation to develop target therapies for visceral hypersensitivity.
Today, it is possible to derive organoids from intestinal crypts harvested from human
intestinal or colonic tissue. The organoids have all epithelial cell types, including gut
sensory cells. Here, the investigator's goal is to use de-identified human tissues to culture
intestinal organoids in the laboratory, and use it as a platform to study the biology of
innervated sensory epithelial cells. This work is significant because it will open the
possibility to learn the mechanisms behind visceral sensation and neurodegenerative diseases
that may arise in the gut.
Inclusion Criteria:
- All patients undergoing either endoscopy OR colonoscopy OR both procedures will be
eligible for inclusion in this study.
- adult males and females 18 years of age or older who have been seen by the GI clinic
or who have been scheduled for direct-to-procedure appointment in the GI clinic.
Exclusion Criteria:
- Subjects who are not competent to give consent
- Males and females under 18 years of age
- Women who are pregnant
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