# A novel live biologic for the prevention and treatment of NEC-induced neurodevelopmental impairment

> **NIH NIH R01** · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · 2024 · $683,916

## Abstract

SUMMARY: Worldwide, up to 25% of premature infants born prior to 31 weeks gestation, and up to 50% of
those born prior to 28 weeks gestation, have neurodevelopmental impairment (NI). The causes of NI are
multifactorial, but neuroinflammation is now recognized as a key component. Early life stresses commonly
encountered by premature infants, including hypoxia, forced formula feeding, and hypothermia, have the
potential to trigger inflammation throughout the body. This inflammation can originate in the intestine, e.g. during
neonatal necrotizing enterocolitis (NEC), where the microbiota incite a dysregulated inflammatory response.
Excessive inflammation in the periphery propagates neuroinflammation and subsequent long-term NI. We have
developed a novel, tunable probiotic delivery system in which the probiotic Limosilactobacillus reuteri (Lr) is
administered in a protective biofilm on biocompatible porous microspheres that provide Lr with cargos that induce
beneficial properties. Administration of Lr in this biofilm state reduces the incidence of NEC and subsequent
neuroinflammation in a rat model after just a single dose. The central hypothesis of this proposal is that
identifying the extent to which Lr antimicrobial and/or anti-inflammatory properties attenuates NI can be
leveraged to tune these Lr properties to optimally prevent, or even treat, NEC-induced NI. Studying the
neurodevelopmental impacts of optimized dosing regimens on both NEC and healthy control pups will
demonstrate the contributions of these properties towards not only preventing and treating NEC-induced NI, but
also healthy neurodevelopment. These studies are in line with the recent NOFO (PAR-23-130) for Translational
Research in Maternal and Pediatric Pharmacology and Therapeutics, where we intend to develop an FDA
approved probiotic formulation which can be administered to all premature infants at risk of developing NEC.
AIM 1: Determine the extent to which Lr antimicrobial pathways can prevent NEC-induced
neurodevelopmental impairment (NI). Bacterial dysbiosis can incite inflammatory responses in the periphery
and brain. We hypothesize that tuning Lr antimicrobial activity can prevent NEC-induced NI.
AIM 2: Determine the extent to which Lr anti-inflammatory pathways can prevent NEC-induced NI. We
will determine the extent to which Lr anti-inflammatory pathways prevent neuroinflammation and subsequent NI.
We hypothesize that tuning Lr anti-inflammatory properties can prevent NEC-induced NI.
AIM 3: Determine the dominant Lr-dependent pathways for the prevention and treatment of NI using all
proven cargos. We will determine whether Lr antimicrobial or anti-inflammatory pathways are dominant,
antagonistic, additive or synergistic in the prevention and treatment of NI. We hypothesize that tuning the best
combinations of Lr pathways can be used to both prevent and treat NEC-induced NI.
The significance of the proposed research is that it will lead to a better understanding of the ab...

## Key facts

- **NIH application ID:** 11027970
- **Project number:** 1R01HD116839-01
- **Recipient organization:** RESEARCH INST NATIONWIDE CHILDREN'S HOSP
- **Principal Investigator:** GAIL E BESNER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $683,916
- **Award type:** 1
- **Project period:** 2024-09-19 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11027970

## Citation

> US National Institutes of Health, RePORTER application 11027970, A novel live biologic for the prevention and treatment of NEC-induced neurodevelopmental impairment (1R01HD116839-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11027970. Licensed CC0.

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