R01AI196346

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 dataset, 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.

Sloan-Kettering Institute For Cancer Research

<P>THE GOALS ARE:</P><UL><LI>TO FOSTER FUNDAMENTAL CREATIVE DISCOVERIES, INNOVATIVE RESEARCH STRATEGIES, AND THEIR APPLICATIONS AS A BASIS FOR ULTIMATELY PROTECTING AND IMPROVING HEALTH;</LI><LI>TO DEVELOP, MAINTAIN, AND RENEW SCIENTIFIC HUMAN AND PHYSICAL RESOURCES THAT WILL ENSURE THE NATION'S CAPABILITY TO PREVENT DISEASE;</LI><LI>TO EXPAND THE KNOWLEDGE BASE IN MEDICAL AND ASSOCIATED SCIENCES IN ORDER TO ENHANCE THE NATION'S ECONOMIC WELL-BEING AND ENSURE A CONTINUED HIGH RETURN ON THE PUBLIC INVESTMENT IN RESEARCH; AND</LI><LI>TO EXEMPLIFY AND PROMOTE THE HIGHEST LEVEL OF SCIENTIFIC INTEGRITY, PUBLIC ACCOUNTABILITY, AND SOCIAL RESPONSIBILITY IN THE CONDUCT OF SCIENCE.</LI></UL><P>IN REALIZING THESE GOALS, THE NIH PROVIDES LEADERSHIP AND DIRECTION TO PROGRAMS DESIGNED TO IMPROVE THE HEALTH OF THE NATION BY CONDUCTING AND SUPPORTING RESEARCH:</P><UL><LI>IN THE CAUSES, DIAGNOSIS, PREVENTION, AND CURE OF HUMAN DISEASES;</LI><LI>IN THE PROCESSES OF HUMAN GROWTH AND DEVELOPMENT;</LI><LI>IN THE BIOLOGICAL EFFECTS OF ENVIRONMENTAL CONTAMINANTS;</LI><LI>IN THE UNDERSTANDING OF MENTAL, ADDICTIVE AND PHYSICAL DISORDERS; AND</LI><LI>IN DIRECTING PROGRAMS FOR THE COLLECTION, DISSEMINATION, AND EXCHANGE OF INFORMATION IN MEDICINE AND HEALTH, INCLUDING THE DEVELOPMENT AND SUPPORT OF MEDICAL LIBRARIES AND THE TRAINING OF MEDICAL LIBRARIANS AND OTHER HEALTH INFORMATION SPECIALISTS.</LI></UL>

93.855 - Allergy and Infectious Diseases Research

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

New York, New York 100656007 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-25-301)