Pathobiomes in Gut of Critically Ill Patients

Despite powerful antibiotics, 50% of the intestinal tracts of critically ill surgical patients are colonized by Pseudomonas aeruginosa, whose mere presence in this site increases mortality fourfold by mechanisms that remain unknown. Many patients who survive the initial surgical trauma still succumb to multi-organ failure and septicemia secondary to an invasive nosocomial infection. The sequelae of shock, hypoxia, and parental nutrition result in injury to the intestinal mucosa, changes in gut permeability, and failure of intestinal defense mechanisms. These conditions put patients at risk for infection and multiple organ failure secondary to the translocation of enteric bacteria, initiating a systemic release of inflammatory mediators-a process that has been termed gut-derived sepsis.

Intestinal P. aeruginosa senses host factors released during stress and responds by activating its virulence gene machinery. As such, the presence of a highly activating intestinal milieu serves to induce virulence in strains of P. aeruginosa and this correlates to the severity of a patient's illness. While the host-pathogen interaction is a dynamic process, the study expects that as a patient's illness worsens or resolves over time, the "virulence-activating" properties of their intestinal milieu will change accordingly. This study will conduct a prospective observational trial in a population of critically ill patients at the Universtiy of Chicago Medical Center. This trial will entail collecting and screening stool samples obtained from critically ill patients for their virulence inducing capabilities on laboratory strains of P. aeruginosa using in vitro and in vivo assays. The study also plans to isolate strains of intestinal P. aeruginosa from stool samples to determine the prevalence of intestinal P. aeruginosa in a population of critically ill patients.

Study Overview

• Status: Recruiting
• Conditions: Pseudomonas Aeruginosa
• Intervention / Treatment: Other: P. aeruginosa using in vitro and in vivo assays

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Leila Yazdanbakhsh, MSCI; Phone Number: 773-834-5087; Email: leila.yazdanbakhsh@bsd.uchicago.edu
• Study Contact Backup: Name: John Alverdy, MD FACS FSIS; Phone Number: 773-702-4876; Email: jalverdy@bsd.uchicago.edu

Study Locations

• United States
  • Illinois
    • Hyde Park, Illinois, United States, 60637
      • Recruiting
      • The University of Chicago
      • Contact: John Alverdy, MD FACS FSIS; Phone Number: 773-834-5087
      • Contact: Leila Yazdanbakhsh, MD FACS FSIS; Phone Number: 7738345087; Email: leila.yazdanbakhsh@bsd.uchicago.edu
      • Principal Investigator: John Alverdy, MD FACS FSIS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

All patients admitted to the burn intensive care unit (BICU), surgical intensive care unit (SICU), and the medical intensive care unit (MICU) longer than 24 hours at University of Chicago Medical Center and are expected to have a prolonged course of care will be recruited into the study.

Description

Inclusion Criteria:

• Any ethnicity
• Age > 18 years and < 85 years

Exclusion Criteria:

• A known history of HIV/AIDS
• Active pregnancy
• Are incarcerated will be excluded from the study.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Critically Ill Patients; All patients admitted to the burn intensive care unit (BICU), surgical intensive care unit (SICU), and the medical intensive care unit (MICU) longer than 24 hours at University of Chicago Medical Center

Other: P. aeruginosa using in vitro and in vivo assays; This trial will entail collecting and screening stool samples obtained from critically ill patients for their virulence inducing capabilities on laboratory strains of P. aeruginosa using in vitro and in vivo assays. The investigators also plan to isolate strains of intestinal P. aeruginosa from stool samples to determine the prevalence of intestinal P. aeruginosa in a population of critically ill patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
In vitro pyocyanin screening assay to determine if a stool sample has any virulence inducing ability on laboratory strains of P. aeruginosa	Through study completion, an average of 3 years
In vivo C. elegans lethality model to determine if liquid media culture "spiked" with stool sample filtrate will induce a lethal phenotype in laboratory strains of P. aeruginosa	Through study completion, an average of 3 years
PCR array analysis of known P. aeruginosa virulence genes following exposure to stool sample filtrate deemed to be highly activating by the in vitro pyocyanin assay and in vivo C. elegans lethality model.	Through study completion, an average of 3 years

Collaborators and Investigators

• Sponsor: University of Chicago
• Collaborators: National Institutes of Health (NIH); National Institute of General Medical Sciences (NIGMS)
• Investigators: Principal Investigator: John Alverdy, MD FACS FSIS, University of Chicago

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2024
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: January 28, 2025
• First Submitted That Met QC Criteria: February 11, 2025
• First Posted (Actual): February 12, 2025

Study Record Updates

• Last Update Posted (Actual): February 2, 2026
• Last Update Submitted That Met QC Criteria: January 29, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Negative Bacterial Infections; Pseudomonas Infections; Investigative Techniques; In Vitro Techniques
• Other Study ID Numbers: 16494B; 5R01GM062344-23 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No