# The small intestinal microbiota in undernourished women and undernourished children in Bangladesh: identifying causal mechanisms and therapeutic targets

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2021 · $1,060,905

## Abstract

PROJECT SUMMARY/ABSTRACT
Childhood undernutrition is a global health challenge manifested by impaired ponderal growth (wasting/acute
malnutrition), impaired linear growth (stunting), immune and metabolic dysfunctions, altered CNS development
plus other abnormalities. >30M children worldwide suffer from moderate acute malnutrition (MAM) with
prevalence anticipated to worsen significantly with the COVID-19 pandemic. Globally, 159M children are
stunted. Current treatments have limited effectiveness. By analyzing serially collected fecal samples from
healthy members of Bangladeshi birth cohorts and those with MAM, we found that MAM is associated with
impaired microbiota development (microbiota immaturity). We have developed a microbiota-directed
formulation of complementary foods that repairs their microbiota, resulting in significantly greater
improvements in ponderal growth compared to an existing nutritional intervention, and revealing mechanisms
by which microbiota members are linked to host mediators of healthy growth. The role of the small intestinal
(SI) microbiota in childhood undernutrition remains enigmatic in part because of the difficulty in obtaining
samples. Associations between altered SI absorptive function, asymptomatic enteropathogen infection and
stunting, have led to the hypothesis that subclinical enteric dysfunction contributes to growth faltering.
Environmental enteric dysfunction (EED) is a SI enteropathy of unknown etiology first described in adult Peace
Corps volunteers, returning from areas of high fecal-oral contamination, with diarrhea, intestinal malabsorption,
reduced villus height/number and gut barrier function disruption. Studies of EED have relied on non-validated
fecal or plasma biomarkers making its contribution to childhood undernutrition ill-defined. Our Bangladesh
Environmental Enteric Dysfunction (BEED) study involved endoscopy of stunted children who failed a
nutritional intervention, which revealed a group of SI bacterial taxa whose absolute abundances negatively
correlate with linear growth; a cultured consortium of these duodenal taxa produced SI enteropathy in recipient
gnotobiotic mice. We now propose to test the hypothesis that the SI microbiota contributes to SI enteropathy
and malnutrition (low-BMI) in women of childbearing age and, via transmission to their children, to perpetuate
intergenerational undernutrition. Our 4 specific aims will compare the SI microbiota plus the duodenal mucosal
and plasma proteomes of malnourished Bangladeshi women (BMI<18.5kg/m2) of child-bearing age with
histopathologic evidence of enteropathy versus those with normal BMIs (20-24.9kg/m2) and no histopathologic
evidence of enteropathy, determine whether their SI microbiota transmits SI enteropathy and impaired growth
to gnotobiotic mice, ascertain whether these phenotypes are prevented/rescued by SI microbial community
members from normal-BMI Bangladeshi women without enteropathy, and screen biochemically-diverse plant
p...

## Key facts

- **NIH application ID:** 10345378
- **Project number:** 1R01DK131107-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** JEFFREY I GORDON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,060,905
- **Award type:** 1
- **Project period:** 2021-09-21 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10345378

## Citation

> US National Institutes of Health, RePORTER application 10345378, The small intestinal microbiota in undernourished women and undernourished children in Bangladesh: identifying causal mechanisms and therapeutic targets (1R01DK131107-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10345378. Licensed CC0.

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