# Unraveling the biological state of children with Environmental enteric dysfunction

> **NIH NIH F30** · WASHINGTON UNIVERSITY · 2022 · $51,752

## Abstract

PROJECT SUMMARY/ABSTRACT
Affecting more than 795 million children under the age of 5, childhood undernutrition is one of the greatest
impediments to the flourishing of humankind. Current dietary interventions fail to ameliorate many of the long-
term sequelae of undernutrition, including linear growth-faltering (‘stunting’) and abnormal central nervous
system (CNS) development. This failure suggests that our understanding of the biological state of undernutrition
is incomplete, and that traditional food therapies fail to target key drivers of undernutrition-dependent pathologies
that manifest later in life. Work from our lab has provided the first evidence that impaired development of the gut
microbiota plays a causal role in stunting. Thus, a multi-dimensional view of childhood undernutrition that
considers several axes of biological state may be required to move the needle on stunting and abnormal CNS
development seen in undernourished children. Recently, a highly prevalent but poorly understood condition
known as Environmental enteric dysfunction (EED) has been found to cause 45% of childhood stunting globally.
Aside from growth-faltering, children with EED are typically asymptomatic; thus, EED is diagnosed by biopsy
and histopathologic evidence of villous blunting, crypt hyperplasia, and chronic inflammatory infiltration within
the sub-lamina propria of the small intestine. Due to the challenge of obtaining upper-intestinal biopsies from
children in a global health setting, most studies have relied on plasma or fecal markers (rather than histologic
evidence) indicating an underlying enteropathy, severely muddling our understanding of EED pathogenesis. In
addition, no validated model of EED exists, further hampering our ability to develop biomarkers and treatments
for EED. The goal of this proposal is to take on a multi-dimensional view of children with biopsy confirmed EED
in order to understand the molecular and microbial features that underly EED pathogenesis and that may serve
as novel biomarkers and therapeutic targets. Employing proteomic and culture-independent methods to survey
the biological state of children with EED, the first aim in this proposal will identify differences between healthy
children and children with EED, determine the proteomic co-abundance network between the plasma and
duodenal compartments of children with EED, and identify putative EED-causal upper-intestinal microbes that
co-vary with duodenal proteins indicative of inflammation and injury. Leveraging the ability to manipulate
microbial community composition and nutrient landscape in gnotobiotic mice, the second aim of this proposal
will test the causality of the upper-intestinal microbiota in EED pathogenesis through a longitudinal study
introducing microbes cultured from the upper-intestinal tract of children with EED and by sequentially removing
members of this community and assessing the effects on host enteropathy. Successful completion of this
proposal wil...

## Key facts

- **NIH application ID:** 10347356
- **Project number:** 5F30DK124967-03
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Robert Yuzen Chen
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $51,752
- **Award type:** 5
- **Project period:** 2020-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10347356

## Citation

> US National Institutes of Health, RePORTER application 10347356, Unraveling the biological state of children with Environmental enteric dysfunction (5F30DK124967-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10347356. Licensed CC0.

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