# Loss of Gastrointestinal Colonization Resistance and Antibiotic-Resistant Infections in the Intensive Care Unit

> **NIH NIH K23** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $127,662

## Abstract

7. PROJECT SUMMARY/ABSTRACT
This proposal details a comprehensive four year training program to expand my clinical and translational
research related to loss of gastrointestinal colonization resistance and the subsequent development of
multidrug resistant (MDR) bacterial infections in the intensive care unit (ICU), as well as extensive didactic and
laboratory-based training in biostatistics and microbiome analysis and methodology. The central hypothesis of
this research proposal is that antibiotic resistance in the ICU is a problem of the human gastrointestinal
microbiome, and that loss of gastrointestinal colonization resistance within the microbiome leads to antibiotic-
resistant infections in at-risk patients. Although colonization resistance cannot be directly measured in vivo, it
can be assessed through surrogate markers: loss of normal fecal biodiversity, domination by multidrug-
resistant organisms (MDROs), and a rise in the total burden of antibiotic resistance genes within the
gastrointestinal microbiome. The overall goal of the research is to identify the clinical and gut microbiome-
related factors that contribute to loss of colonization resistance in order to facilitate strategies to prevent gut-
derived MDR infections in the ICU. To accomplish this, I will perform a prospective cohort study in ICU
patients with collection of samples and clinical data at the time of ICU admission and 72 hours later. Using the
samples and data collected, I will then determine (1) the clinical exposures that lead to loss of gastrointestinal
colonization resistance in the ICU; (2) the specific bacterial taxa that preserve gastrointestinal colonization
resistance in the ICU; and (3) the impact of antibiotics on the total burden of gastrointestinal antibiotic
resistance in the ICU. The results of this research will delineate the key risk factors for loss of colonization
resistance, and will form the foundation for future multicenter trials for the prevention of MDR infections in the
ICU and in other at-risk settings. Through the proposed complementary career development plan, I will gain
additional training in advanced statistical analysis, and the laboratory-based and didactic training in the
analysis of the microbiome necessary in order to develop a long-term research program to understand the
relationship between the gut microbiome and MDR or other opportunistic infections. Throughout this research
and these career development activities, I will be mentored by a team led by Dr. Timothy Wang, an
internationally recognized scientist and expert in how gastrointestinal microorganisms can cause human
disease. I am committed to a career as an independent investigator in patient oriented research and have
constructed my training plan to provide the knowledge and skills needed to make substantial contributions to
identifying and modifying the risk factors for gut-derived infections.

## Key facts

- **NIH application ID:** 9843504
- **Project number:** 5K23DK111847-04
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Daniel E. Freedberg
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $127,662
- **Award type:** 5
- **Project period:** 2017-02-17 → 2020-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9843504

## Citation

> US National Institutes of Health, RePORTER application 9843504, Loss of Gastrointestinal Colonization Resistance and Antibiotic-Resistant Infections in the Intensive Care Unit (5K23DK111847-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9843504. Licensed CC0.

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