Gut-Brain-Axis/Lung-Brain-Axis and Mental Ill Health in Critical Illness

Survivors of critical illness commonly experience long-lasting cognitive, mental health and physical impairments. Clinically significant symptoms of anxiety, depression, and post-traumatic stress disorder (PTSD) may occur in 40%, 34% and 20% of ICU survivors respectively, compared to 6%, 8% and 4% in the general population. These symptoms can persist for more than 8 years.

Evidence shows the existence of a two-way, communication network between gut microbes and the brain referred to as the gut-brain axis. Changes in the microbiome and dysregulation of this communication network in relatively healthy people is associated with cognitive dysfunction and mood disorders such as anxiety and depression. The physiological stress associated with critical illness itself and many ICU interventions including the use of mechanical ventilation and medications such as antibiotics, antacids, vasopressors, and steroids can influence the balance of the gut microbiome and associated metabolites.

This observation study aims to:

1. Quantify and measure dynamic changes in the gut microbiome and its metabolites during critical illness and recovery.
2. Explore the associations between microbiome and metabolomic changes during critical illness and psychological symptoms in the patient during their recovery.

This knowledge will provide the potential to create interventions that alter the gut environment and microbiome both during and following a critical illness in order to reduce long-term adverse psychological effects. Examples of such potential interventions include dietary modifications with the use of prebiotics or probiotics.

Study Overview

• Status: Recruiting
• Conditions: Critical Illness; Mental Health Issue; Gut Microbiome

• Study Type: Observational
• Enrollment (Anticipated): 60

Contacts and Locations

• Study Contact: Name: Rebecca Cusack; Phone Number: 023 8120 5308; Email: rebecca.cusack@uhs.nhs.uk

Study Locations

• United Kingdom
  • Southampton, United Kingdom
    • Recruiting
    • University Hospital Southampton NHS Foundation Trust
    • Contact: Rebecca Cusack

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with an unplanned admission to critical care who are mechanically ventilated

Description

Inclusion Criteria:

• Unplanned admission to critical care
• Aged ≥18 years old
• Requiring mechanical ventilation
• Commencing ventilation within the previous 24 hours
• Expected to be ventilated for minimum of ≥72 hours

Exclusion Criteria:

• Known prior diagnosis of cognitive impairment
• Known prior mental ill health
• Known malignancy
• Admitted after presenting with any of the following conditions:
• trauma
• brain injury
• surgery
• cardiac arrest
• immunosuppressed
• underlying pyogenic infection
• Not expected to survive to completion of the study

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut microbiome changes	Quantify and measure dynamic changes in the gut microbiome and its metabolites during critical illness and recovery. (The number and diversity of microbe present)	3 months post-discharge
Microbiome, metabolic changes and psychological symptoms	Explore the associations between microbiome and metabolomic changes during critical illness and psychological symptoms in the patient during their recovery.	3 months post-discharge
Gut microbial and metabolic signatures	Investigate the potential for gut microbial and metabolic signatures at admission and discharge to predict the future development of psychological symptoms following ICU discharge.	3 months post-discharge
Sample repository	Establish a sample repository for future analysis for future studies.	3 months post-discharge

Collaborators and Investigators

• Sponsor: University Hospital Southampton NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2023
• Primary Completion (Anticipated): November 1, 2024
• Study Completion (Anticipated): November 1, 2024

Study Registration Dates

• First Submitted: October 11, 2022
• First Submitted That Met QC Criteria: October 11, 2022
• First Posted (Actual): October 14, 2022

Study Record Updates

• Last Update Posted (Actual): April 14, 2023
• Last Update Submitted That Met QC Criteria: April 12, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness
• Other Study ID Numbers: RHM CRI0428

Drug and device information, study documents

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