Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Metabolite-Driven Strategies to Strengthen the Premature Intestine

Award Number: K08DK149531
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 05/31/2031

Group Awards By:

View Award Description

Metabolite-Driven Strategies to Strengthen the Premature Intestine - PROJECT SUMMARY Necrotizing enterocolitis (NEC) is a devastating intestinal disease that affects approximately 10% of premature infants, of whom up to half require surgery and 30–50% die from complications. Despite decades of research, there are no effective therapies; management remains limited to bowel rest, antibiotics, and supportive care once disease is already established. The gastrointestinal tract develops primarily during the second and third trimesters; therefore, premature infants are born with structurally and functionally immature intestinal barriers that are ill-equipped to defend against microbial invasion and inflammation. Deficiencies in epithelial integrity, mucus production, microbial colonization, and immune defense are fundamental drivers of NEC pathogenesis. Current preventive and therapeutic strategies target inflammation but fail to address the underlying developmental immaturity of the premature gut—a critical gap that continues to limit progress in the field. This proposal seeks to address that gap by targeting pathways that drive epithelial differentiation and barrier maturation, thereby enhancing the premature gut’s intrinsic defenses. Our central hypothesis is that microbial metabolite Urolithin A (UroA) and its potent synthetic analogue UAS03, through activation of the aryl hydrocarbon receptor (AhR) pathway, will accelerate gastrointestinal development and decrease susceptibility to NEC. Aim 1 will determine whether UroA/UAS03 supplementation during pregnancy and early infancy promotes goblet cell differentiation, mucus barrier formation, and microbial diversity, using a pre-clinical mouse model of NEC-like intestinal injury. Aim 2 will define whether AhR activation is required for goblet cell differentiation and mucus barrier function using a translational human intestinal enteroid model derived from premature infants. This work is innovative because it shifts the NEC research paradigm from treating inflammation to promoting gut maturation as a preventive strategy. By leveraging a safe, naturally occurring microbial metabolite already used in humans, this project introduces a novel application of AhR signaling to neonatal gastrointestinal development. If successful, these studies will define the first strategy to pharmacologically enhance intestinal maturation and resilience in premature infants. The proposed research has the potential to transform neonatal care by reducing the incidence and severity of NEC, improving survival, and decreasing the lifelong complications of intestinal failure and neurodevelopmental impairment. Beyond its translational potential, this work will advance fundamental understanding of intestinal development and host– microbiota interactions—areas of broad relevance to gastrointestinal developmental biology and neonatal health.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $167,280 )
2026	2026	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	7/16/2026	NEW	$167,280
														Subtotal = $167,280

Grand Total All Awards = $167,280

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Metabolite-Driven Strategies to Strengthen the Premature Intestine

Award Number: K08DK149531

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 05/31/2031

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer