# Role of short chain fatty acids in intestinal barrier maturation in preterm infants

> **NIH NIH R21** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $193,125

## Abstract

PROJECT SUMMARY
Necrotizing enterocolitis (NEC) is a life-threatening, gastrointestinal (GI) emergency affecting 7-10% of preterm
infants with mortality as high as 30-50%. "Leaky gut", or intestinal barrier immaturity with elevated intestinal
permeability (IP), is the proximate cause of susceptibility to NEC in preterm neonates. Early detection of leaky
gut is essential to identify infants at risk for NEC to prevent and reduce disease severity. No clinical factor,
routine laboratory test or biomarker alone or in combination have been described that identify preterm
neonates with impaired intestinal barrier function who at increased risk for NEC. The goal of this study is to
develop a rapid, non-invasive screening tool to identify “at-risk" preterm infants prior to the onset of NEC. We
recently revealed rapid maturation of the intestinal barrier is strongly associated with clinical factors such as
early breastmilk feeding, less antibiotic exposure and later post-menstrual age, and significantly higher
abundance and metabolic activities of Clostridiales and Bifidobacterium. Although the butyrate producing
Clostridiales have been implicated in strengthening the intestinal epithelial barrier and reducing intestinal
inflammation, it is unknown whether butyrate and potentially other short chain fatty acids (SCFAs) are
associated with neonatal intestinal barrier maturation. Our preliminary data revealed butyrate production
pathways, in particular Pyruvate/Acetyl-CoA pathway are significantly more abundant in low IP subjects. In this
study, we propose to validate a substantiated measure of fecal microbial and/or metabolic biomarkers
combined with associated neonatal factors for a rapid, non-invasive screening test. We postulate that the
level(s) of metabolic activities, particularly butyrate production and potentially other SCFAs via increased
colonization of Clostridiales and Bifidobacterium, are associated with intestinal barrier maturation in preterm
neonates. To address our hypothesis, we will leverage existed stool samples collected from a cohort of ~200
preterms (<33 weeks), for whom both microbiota (16S rRNA gene sequencing) and IP (urine non-metabolized
sugar probes lactulose and rhamnose) are available, and propose 2 aims: 1) to determine fecal metabolic
activities associated with intestinal barrier maturation in preterm neonates <33 weeks gestation; and 2) to
identify and characterize butyrate-producing bacteria associated with intestinal permeability in preterm
neonates during the first 7-10 days of life. At the completion of the study, we will determine the biomarkers
associated with healthy intestinal barrier functions and the discriminatory scheme for accurate classification of
high or low IP group. Our long-term goal is to conduct a randomize clinical trial of rationally designed
intervention for NEC early prevention. Refinement of the screening tool will identify infants with aberrant leaky
gut, an essential prerequisite for subsequent ra...

## Key facts

- **NIH application ID:** 10018932
- **Project number:** 5R21DK123674-02
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Bing Ma
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $193,125
- **Award type:** 5
- **Project period:** 2019-09-16 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10018932

## Citation

> US National Institutes of Health, RePORTER application 10018932, Role of short chain fatty acids in intestinal barrier maturation in preterm infants (5R21DK123674-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10018932. Licensed CC0.

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