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

Study Overview
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Brief Summary
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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: Quantify and measure dynamic changes in the gut microbiome and its metabolites during critical illness and recovery. 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.

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

Conditions
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Mental Health Issue, Critical Illness, Gut Microbiome

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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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 |