# Mechanisms of Gastrointestinal Post-Inflammatory Disease

> **NIH NIH R01** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2021 · $342,000

## Abstract

ABSTRACT:
Diarrhea-predominant, irritable bowel syndrome (IBS-D) is one of the most frequent
gastrointestinal disorders seen and is characterized by abdominal pain, loose watery stools, and
urgency in the absence of an identifiable inflammatory, structural, or metabolic abnormality. One
of the most common and difficult to treat IBS-D groups are those who contract an enteric
infection from food poisoning and subsequently develop post-infectious, diarrhea-predominant,
irritable bowel syndrome (PI-IBS-D). The mechanisms of persistent diarrhea and visceral
nociception following resolution of the colitis are unclear and further work is needed to
understand its pathophysiology. It puts an enormous financial burden on health care resources
and decreases quality of life. Unfortunately, pharmacologic therapies for PI-IBS-D remain
limited and unsatisfactory. Therefore, we are focusing on this subpopulation of patients to study
the underlying mechanisms of post-colitis gastrointestinal dysfunction.
 We now have preliminary data that provide a very strong rationale for a role for the cAMP-
response element transcription factor (CREB) and miRNAs, leading to decreased opioid gene
expression in PI-IBS-D patients. Enteric infections alter gastrointestinal function and visceral
nociception leading to PI-IBS-D. We have identified miRNAs in PI-IBS-D patients that are
modulated by CREB signaling pathways, that target downstream opioid genes in the colonic
enteric nervous system and that control post-inflammatory regulation of gastrointestinal function
and visceral nociception. We hypothesize that miRNAs dysregulate downstream targets
following an enteric infection through altered CREB signaling pathways. These new findings
suggest that PI-IBS-D involves dysregulation of complex regulatory pathways in which miRNAs
interact through downstream targets. Our lab has established innovative techniques to
determine inter- and intra-cellular roles of miRNAs in the epigenetic regulation of the expression
of their down-stream target genes. These methods include interaction analysis of miRNAs; in
vitro transfection of miRNAs; and in vivo injection of miRNAs oligonucleotides. These findings
will (i) shed light on the mechanisms of dysregulation of gastrointestinal function in PI-IBS-D
patients; (ii) overcome a critical barrier to progress in the management of patients following
enteric infection and colitis–absence of effective treatment interventions; (iii) lead to preventive
and/or therapeutic strategies in PI-IBS-D patients that mimic or inhibit the effects of specific
miRNAs on target gene expression.

## Key facts

- **NIH application ID:** 10190923
- **Project number:** 5R01DK118959-03
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** George Nicholas Verne
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $342,000
- **Award type:** 5
- **Project period:** 2020-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10190923

## Citation

> US National Institutes of Health, RePORTER application 10190923, Mechanisms of Gastrointestinal Post-Inflammatory Disease (5R01DK118959-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10190923. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*