# Dysbiosis in Hirschsprung Associated Enterocolitis Pathogenesis

> **NIH NIH R01** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2021 · $403,698

## Abstract

Hirschsprung-associated enterocolitis (HAEC) is a life-threatening complication of Hirschsprung Disease
(HSCR), a common cause of intestinal obstruction in the newborn that results from incomplete development of
the enteric nervous system (ENS). HAEC affects 30-60% of infants with HSCR, occurs with unchanged incidence
pre- and post-operatively, and carries a mortality of 5-10%, with the majority of deaths occurring in newborns
prior to definitive operation. A critical barrier in the field is that the etiology of HAEC is poorly defined and current
treatment remains empiric (bowel rest, rectal washouts, broad-spectrum antibiotics) and directed toward
alleviating acute symptoms rather than targeting underlying pathophysiology. The long-term goal of our research
is to define the pathophysiology of HAEC in order to develop novel therapeutic approaches that reduce morbidity
and mortality in HSCR patients. Our preliminary and published findings, reinforced by those of other laboratories,
support the central hypothesis that perturbation of host-microbiome mutualism, including evasion of immune
exclusion and reinforcement of intestinal stasis by dysbiotic microbiota, drives the development of HAEC. Our
objectives are to 1) define the mechanisms for impaired IgA production and secretion in HAEC, 2) identify the
disease-promoting members of the dysbiotic HAEC microbiome, and 3) determine how the HAEC microbiome
reinforces intestinal stasis. The proposed research is innovative because it will utilize novel, preclinical models
to establish a causative relationship between dysbiosis and HAEC pathogenesis and test potential therapeutic
targets. Our group is uniquely qualified to complete the aims because of our expertise in HSCR & HAEC, host-
microbiome interactions, microbial endocrinology, and intestinal epithelial cell biology. The expected outcome of
these studies will be a deeper understanding of the pathophysiology of HAEC and identification of novel
therapeutic approaches for prevention or treatment of HAEC.

## Key facts

- **NIH application ID:** 10135960
- **Project number:** 5R01DK125047-02
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** Ankush Gosain
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $403,698
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10135960

## Citation

> US National Institutes of Health, RePORTER application 10135960, Dysbiosis in Hirschsprung Associated Enterocolitis Pathogenesis (5R01DK125047-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10135960. Licensed CC0.

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