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Understanding and manipulating microbiome ecology to curb gut-borne infections.

Award Number: R01AI196346
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2026
PERIOD OF PERFORMANCE END DATE: 02/28/2030

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Understanding and manipulating microbiome ecology to curb gut-borne infections. - SUMMARY/ABSTRACT Gut-borne bloodstream infections are a significant cause of morbidity and mortality in immunocompromised patients, often leading to sepsis and poor clinical outcomes. Despite their severity, current clinical approaches rely on reactive antibiotic treatments, which fail to address the root cause—disruptions in the gut microbiome that allow opportunistic pathogens to expand and enter the bloodstream. This project will develop a proactive, microbiome-based strategy that leverages machine learning and ecological modeling to predict, prevent, and mitigate these infections before they occur. Our collaborative team has pioneered mathematical modeling and microbiome research, integrating longitudinal clinical data, ecological theory, and experimental validation to uncover the dynamics of microbiome resilience and infection risk. We have assembled a large clinical microbiome datasets, spanning over 1,000 immunocompromised patients, demonstrated that gut microbiome disruptions predict bloodstream infection risk, and conducted trials to restore microbiome composition for improving clinical outcomes. This application will translate these insights into actionable clinical tools by leveraging our expertise and data infrastructure. We will develop computational models to (1) forecast infection risk based on microbiome dynamics, (2) optimize antibiotic stewardship to minimize collateral damage to beneficial gut bacteria, and (3) design precision probiotics to restore microbiome defenses. This integrative approach combines large-scale clinical data analysis, computational modeling, and experimental validation using both in vitro and in vivo models to advance our mechanistic understanding of gut microbiome ecology and the molecular processes involved in protection against gut-borne pathogens. This work envisions a future where computational microbiome management becomes a standard tool for preventing gut-borne infections. By shifting the paradigm from reactive to proactive care, our approach can transform infection control, reduce the global burden of antibiotic resistance, and improve outcomes for immunocompromised patients.


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 = $3,519,992 )
2026	2026	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Allergy and Infectious Diseases Research	000	1	2/20/2026	NEW	$3,519,992
														Subtotal = $3,519,992

Grand Total All Awards = $3,519,992

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Understanding and manipulating microbiome ecology to curb gut-borne infections.

Award Number: R01AI196346

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/01/2026

PERIOD OF PERFORMANCE END DATE: 02/28/2030

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