Thursday, January 1, 2026 1/1/2026

A Human Gut-Liver Platform with Microbiome Interactions for In Vitro Toxicology

Award Number: R21ES036001
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/15/2024
PERIOD OF PERFORMANCE END DATE: 12/31/2026

Group Awards By:

View Award Description

A Human Gut-Liver Platform with Microbiome Interactions for In Vitro Toxicology - ABSTRACT While rodents have provided valuable information on key aspects of the gut-liver axis, there are fundamental species-specific differences in the gut-liver axis, such as the composition of the microbiome, differences in liver xenobiotic metabolism, and progression of alcoholic and metabolic fatty liver disease. Therefore, human- relevant in vitro models now play important roles in complementing in vivo animal studies for basic science and for drug screening. While considerable progress has been made in the development of human models of intestine and the liver using physiologically relevant primary cells, very little has been done in engineering an integrated human gut-liver model using primary cells. We have utilized droplet microfluidics to fabricate highly monodisperse extracellular matrix (ECM)-based 3D liver microtissues containing primary human hepatocytes and liver sinusoidal endothelial cells that are rapidly generated and functionally outperform self-assembled hepatic spheroids and hepatocytes within bulk gels for 4+ weeks; furthermore, the microtissues can be further augmented with human hepatic stellate cells and Kupffer cells. We have also separately developed in vitro human intestine models using primary cells, which can be engineered to maintain gradients of O2 across the basal and luminal surfaces to recapitulate the stem cell and differentiated cell compartments of the crypt; can produce mucus; and are amenable to the incorporation of microbiota in the luminal compartment. Here, we will engineer in vitro human gut-liver models of increasing complexities, which will be used to elucidate how intestine, liver, and microbiota interact to modulate reciprocal functions. In aim 1, we will elucidate reciprocal functional changes in a human gut-liver model containing primary human colonocytes and liver cells, while in aim 2 we will introduce mucus and microbiota in the intestinal model and elucidate reciprocal crosstalk upon co-culture with human liver microtissues. This proposal will yield a first-of-its-kind scalable human gut-liver model containing primary cells for in vitro applications, such as compound screening and disease modeling.


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 = $0 )
2026	2025	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Environmental Health	000	2	10/31/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $197,126 )
2025	2025	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Environmental Health	001	2	9/26/2025	NON-COMPETING CONTINUATION	$0
2025	2025	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Environmental Health	000	2	12/11/2024	NON-COMPETING CONTINUATION	$197,126
														Subtotal = $197,126

Issue Date FY: 2024 ( Subtotal = $251,525 )
2024	2024	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Environmental Health	000	1	1/15/2024	NEW	$251,525
														Subtotal = $251,525

Grand Total All Awards = $448,651

Top

All Categories

About

Search

Reports

Data Submission

Award Information

A Human Gut-Liver Platform with Microbiome Interactions for In Vitro Toxicology

Award Number: R21ES036001

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 01/15/2024

PERIOD OF PERFORMANCE END DATE: 12/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer