The Gut Microbiome - Source of Sepsis and Novel Target in Intensive Care Units? (MS-ICU)

The Gut Microbiome - Source of Sepsis and Novel Target in Intensive Care Units? Research on Human Tissue, Body Fluids, Neuropsychological Assessment and Brain Imaging

Here, the investigators propose to study host responses to reduced microbiome complexity driven by treatment with broad spectrum antibiotics in patients with severe infections or sepsis. The proposal aims to combine holistic approaches with emerging experimental technologies to investigate the complex interactions between the gut microbiota and its host and assess the impact of specific bacterial communities on longevity and stress responses. A strong focus of this study will also be placed on microbiome dysbiosis and secondary impacts on short- and long-term brain dysfunction using clinical, laboratory and imaging procedures.

Study Overview

• Status: Recruiting
• Conditions: Sepsis; Critical Illness; Neurocognitive Deficit; Intensive Care Unit Delirium; Infection in ICU; Microbiome,immune Function, Critically Ill

Detailed Description

Prospective observational study to obtain faeces, rectal swabs, and plasma samples from critically ill patients with and without broad spectrum antimicrobial therapy as well as from long-term survivors after sepsis. Furthermore, clinical, neuropsychological and neuroimaging data will be collected to assess short- and long-term brain dysfunction.

Furthermore it will be to correlate metagenomic and metabolomic data analysis from stool and blood samples of ICU patients with clinical outcomes (including the trajectory of neuro-cognitive deficits) and stress-related parameters.

Additionally, the study aims to identify if microbiome dysbiosis is connected to short- and long-term brain dysfunction and to assess which microbiome metabolic products influence brain dysfunction.

Moreover, the investigators aim to explore immune cell diversity through single cell whole transcriptome analysis in order to establish new hypotheses on specific bacteria species and metabolites to affect the immune cell type composition of patients (single cell immuno-profiling) and integrate single cell RNA sequencing with clinical symptoms in critically ill patients.

Finally, the question is addressed whether there are differences between blood cell composition and activation between younger and older patients with and without sepsis.

In this regard, blood- and stool samples will be taken from participants at five time points as follows: three time points during ICU treatment respectively (at study inclusion day 1, day 7 and day 14) and as well as two follow-up surveys (3 and 6 months after inclusion). Brain dysfunction will be assed by daily delirium screening tests (CAM-ICU and ICDSC) and at the time of discharge from hospital by MoCa and Mini Mental Status Examination. At the follow-up survey functional MRI as well as neuropsychological measures will be performed.

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

Contacts and Locations

• Study Contact: Name: Johannes Ehler, Priv.-Doz. Dr. med.; Phone Number: +49 36419323397; Email: johannes.ehler@med.uni-jena.de
• Study Contact Backup: Name: Katrin Ludewig, Dr. med.; Phone Number: +49 36419323378; Email: katrin.ludewig@med.uni-jena.de

Study Locations

• Germany
  • Thüringen
    • Jena, Thüringen, Germany, 07747
      • Recruiting
      • Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum Jena
      • Contact: Johannes Ehler, Priv.-Doz. Dr. med.; Phone Number: +49 3641-9-323397; Email: johannes.ehler@med.uni-jena.de
      • Contact: Katrin Ludewig, Dr. med.; Phone Number: +4936419323378; Email: katrin.ludewig@med.uni-jena.de
      • Contact: Johannes Ehler, Priv.-Doz. Dr. med.
      • Contact: Katrin Ludewig, Dr.med.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

ICU patients with and without antibiotic treatment as well as patients with long-term survival after critical illness

Description

Inclusion Criteria:

• Age ≥ 18 years

• One of the following criteria

  1. Critically ill patients treated with meropenem or piperacillin/tazobactam started within the last 72 h
  2. Critically ill patients without systemic antimicrobial therapy within the last 72 hours and an expected ICU length of stay of more than 3 days
  3. Long-term survivors of sepsis, e.g. from pre-existing sepsis cohorts

Exclusion Criteria:

• Inflammatory bowel disease
• Major bowel resection
• Selective decontamination of the oral and digestive tract
• Oral vancomycin therapy
• Immunocompromised patients
• History of chemotherapy during the last 6 months.
• Known travel history to countries to areas of high antimicrobial resistance (>5% according to the report of the European Centre for Disease Prevention and Control and all countries except USA and Canada) within the last 4 weeks
• Acute neurological diseases (e.g., brain ischemia, hemorrhage, meningoencephalitis, tumor)
• Manifest dementia, pre-existing psychiatric diseases (schizophrenia, psychosis)
• Acute brain surgery
• MRI contraindications: pacemakers, hearing aids, neurostimulation, insulin pumps, other potentially ferromagnetic implants, screws, clips, prostheses, metal splinters, etc., pregnancy, claustrophobia, extensive tattoos.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
ICU patients with antibiotic treatment; ICU patients treated with piperacillin/tazobactam or meropenem
ICU patients without antibiotic treatment; ICU patients without antibiotic treatment during their ICU stay
Long-term survivors of critical illness; Long-term survivors at least six months or more after the beginning of critical illness.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with brain dysfunction	Patients from all three groups will be assessed for microbiome dysbiosis (e.g. shotgun metagenomics), and for brain dysfunction (e.g. CAM-ICU, ICDSC, MoCa, MMST, neuropsychiatric examination, MRI).	From enrollment to day 180

Secondary Outcome Measures

Outcome Measure	Time Frame
Days on the ICU	From enrollment to the end of study at 180 days
Days on the respirator	From enrollment to the end of study at 180 days
Days with vasopressor support	From enrollment to the end of study at 180 days
Number of patients with survival	From enrollment to the end of study at 180 days

Collaborators and Investigators

• Sponsor: Jena University Hospital
• Collaborators: Friedrich Schiller University of Jena
• Investigators: Principal Investigator: Johannes Ehler, Priv.-Doz. Dr. med., Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 27, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: December 23, 2024
• First Submitted That Met QC Criteria: December 23, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 27, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: delirium; sepsis; microbiome; stool; neurocognitive impairment; neuropsychological assessment; broad-spectrum antibiotics
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Pathologic Processes; Disease Attributes; Infections; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Systemic Inflammatory Response Syndrome; Inflammation; Delirium; Critical Illness; Sepsis; Toxemia
• Other Study ID Numbers: 2024-3429-BO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No