# Microbiome Induced Epigenetic Changes in Intestinal Inflammation and Necrotizing Enterocolitis

> **NIH NIH R21** · BAYLOR COLLEGE OF MEDICINE · 2020 · $230,908

## Abstract

PROJECT SUMMARY
In preterm neonates, excessive inflammatory responses have been implicated in necrotizing enterocolitis
(NEC), the mechanisms for which are unclear. Microbiota and their metabolites including short chain fatty acids
may modify the epigenome by DNA methylation and/or histone deacetylation, and specific microbiome patterns
have been associated with altered DNA methylation of genes linked to lipid metabolism, obesity and
inflammation.
 The long term goal of this research is to determine the mechanism for excessive inflammatory responses that
lead to NEC and devise anti-inflammatory therapeutic and preventative strategies. The specific hypothesis of
the proposed research is that epigenetic changes induced by the developing intestinal microbiome result in
excessive immune and inflammatory responses that predispose to necrotizing enterocolitis in the preterm
neonate. We intend to test this hypothesis by first establishing DNA methylation alterations in preterm infants
with NEC compared to matched controls, in a nested cohort clinical design in Specific Aim 1. DNA methylation
patterns will be delineated in intestinal epithelial cells and peripheral blood mononuclear cells and confirm
differential gene expressions with transcriptomics in the intestinal epithelial cells from the stools and assess
systemic and intestinal inflammation. In our second Specific Aim, we will test the hypothesis that specific
microbiome and metabolomic signatures are associated with changes in the epigenome and transcriptome in
preterm neonates with NEC. In the cohort enrolled, we will evaluate stool microbiome by metagenomics and
stool and urine metabolome for microbial metabolites and record clinical metadata (e.g. gestational age,
feeding) for multi-variable analysis. We anticipate distinct microbiome and metabolome signatures associated
with DNA methylation alterations in NEC. Follow up studies of enteroids from surgical samples will be used to
mechanistically test our hypothesis by measuring epigenetic changes after exposure to specific inflammatory,
microbial or metabolomic stimuli that are identified from the proposed research.
The proposed research is innovative as the epigenome alterations in relation to the microbiome and
inflammation in the preterm infant have not been evaluated. We propose a holistic, multi-omics approach to
delineate the mechanisms for excessive inflammation in the preterm infant. Our research will not only make an
impact in the field of neonatology where major organ morbidity is related to inflammation but in also in other
patients and diseases where inflammation is an inciting and key factor in the pathogenesis. Exploring the
relationship between microbiota induced epigenetic changes and inflammatory responses may underpin the
pathophysiology of NEC and lead to novel preventive strategies in the preterm neonate. Our research is
significant because our work will provide new knowledge on microbiome-induced epigenetic changes that is
...

## Key facts

- **NIH application ID:** 9893335
- **Project number:** 1R21HD091718-01A1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Mohan Pammi
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $230,908
- **Award type:** 1
- **Project period:** 2020-06-17 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9893335

## Citation

> US National Institutes of Health, RePORTER application 9893335, Microbiome Induced Epigenetic Changes in Intestinal Inflammation and Necrotizing Enterocolitis (1R21HD091718-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9893335. Licensed CC0.

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