# Role of Immunity and the Microbiota in Enteropathogenic E. coli Eradication

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $386,526

## Abstract

ABSTRACT
Enteric and diarrheal diseases caused by pathogens are important causes of childhood death worldwide.
These diseases are estimated to cause near 1 million deaths per year in children under 5 years old worldwide,
ranking second as the cause of death in this age group. This is largely due to their increased susceptibility of
neonates and young children to enteric infections. In the healthy adult gut, the microbiota provides
“colonization resistance”, forming a barrier against invading pathogens. The increased susceptibility to
infections has been generally ascribed to immaturity of the immune system; however, additional factors may
play an important role because immune responses to different stimuli are highly variable among neonates.
Recent studies in our laboratory showed that the microbiota of neonatal mice is impaired in mediating
colonization resistance against Salmonella and Citrobacter rodentium, a bacterium that models infection by
enteropathogenic E. coli (EPEC), the most common cause of diarrheal deaths by bacteria worldwide. The lack
of colonization resistance was caused by the absence of Clostridiales in the neonatal microbiota. We also
found that IgG, but not IgA, induced after infection recognized surface C. rodentium virulence factors and
bound virulent bacteria within the intestinal lumen leading to their opsonization and engulfment by neutrophils,
while phenotypically avirulent pathogens remained in the intestinal lumen and are out-competed by the
microbiota. Thus, the immune system and the microbiota play cooperative and essential roles in C. rodentium
eradication. In this proposal, we proposed three specific Aims (i) to identify mechanisms by which Clostridia
species mediate inhibition of enteric pathogen in the gut; (ii) understand the mechanisms that promote the
colonization of protective Clostridiales in the neonatal intestine and (iii) determine the mechanism by which
intestinal IgG against C. rodentium virulence factors protects neonates from infection. The proposed studies
have the potential for a major impact on human health and in particular on that of infants and children.

## Key facts

- **NIH application ID:** 9961528
- **Project number:** 5R01DK095782-08
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Gabriel Nunez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $386,526
- **Award type:** 5
- **Project period:** 2013-05-20 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9961528

## Citation

> US National Institutes of Health, RePORTER application 9961528, Role of Immunity and the Microbiota in Enteropathogenic E. coli Eradication (5R01DK095782-08). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9961528. Licensed CC0.

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