Gut-brain Axis, Brain Function, and Behaviour.

Study Overview
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Brief Summary
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The aim is to test if dietary supplementation with prebiotics reduces measures of anxiety in healthy human participants with high self-reported levels of anxiety. Study will test for an effect on behavioural, neuroendocrine and brain imaging markers of anxiety.

Official Title
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Does Stimulating Friendly Gut Bacteria Improve Brain Function and Behaviour?

Conditions
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Prebiotics, Anxiety, Humans, Magnetic Resonance Imaging, Decision Making, Emotion, Cortisol

Intervention / Treatment
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* Dietary Supplement: Prebiotics
* Dietary Supplement: Maltodextrin (placebo)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Trait anxiety levels > 40 on STAI trait inventory Participant is willing and able to give informed consent for participation in the study Not currently taking any psychoactive medications Exclusion Criteria: Pregnant participants No contraindications to prebiotic administration Antibiotic, probiotics and/or prebiotic treatment in at least the two previous months. Participants who are taking any other food supplements that, in the opinion of the Investigators, may affect the results. Participants who are taking any medications that, in the opinion of the Investigators, may affect the results. Any significant change in diet which, at the discretion of the Investigators, may affect the results. Participants who have recently participated in another research trial which, at the discretion of the Investigators, may affect the results. A history of dementia, traumatic brain injury or stroke. Anyone who is unable to perform the behavioural tasks. Current use of any psychoactive medication. Current use of psychological treatment. Anyone who does not have adequate understanding of English, sufficient to give informed consent. Any person who has a history of drug abuse or a previous history of a neurological, or has a history of neurosurgical procedure is excluded as they may be at increased risk of epilepsy and data collected may be influenced by their condition. Anyone with any metal implants or implantable device would be excluded from any brain imaging studies as indicated by the MRI safety screening form.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Crossover Assignment Randomised Double-blind Cross-over design with 4-6 weeks of prebiotics intervention and 4-6 weeks of placebo intervention. The first intervention phase will be followed by a 3 week wash-out period prior to the second intervention phase.d.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Start with prebiotics<br>Half of the participants start with prebiotics, followed by a testing period. After a wash-out period they will continue with placebo followed by a testing period. | Dietary Supplement: Prebiotics<br>* Galactooligosaccharides (GOS) (prebiotics) will be consumed by the participants for 4-6 weeks<br>|
| Experimental: Start with placebo<br>Half of the participants start with placebo, followed by a testing period. After a wash-out period they will continue with prebiotics followed by a testing period. | Dietary Supplement: Maltodextrin (placebo)<br>* Maltodextrin (placebo) will be consumed by the participants for 4-6 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cortisol awakening response (CAR) | CAR, a marker of stress responsivity, should be decreased after taking prebiotics compared to placebo (as previously found in non-anxious participants in Schmidt et al., 2015, Psychopharmacology) | Cortisol awakening responses will be measured at the end of the first intervention phase (4-6 weeks after study entry) and at the end of the second intervention phase (11-15 weeks post study entry). | 
| Brain imaging (BOLD fMRI activity) in amygdala and cortical regions | Brain imaging (BOLD fMRI activity) in amygdala and cortical regions Will provide neural measures of threat reactivity. We predict decreased amygdala and/or increased parietal-prefrontal brain activity after prebiotics compared to placebo, indicating an anxiolytic-like profile (fearful -neutral face trials in the low load condition) (as in Bishop et al, 2007 and Ironside et al, 2017) | Brain imaging will be measured at the end of the first intervention phase (4-6 weeks after study entry) and at the end of the second intervention phase (11-15 weeks post study entry). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in gut microbiome | Availability of specific bacteria in microbiome will change as function of prebiotics and not during placebo. The change will be measured at the start of each intervention compared to the end of each intervention | Changes in the microbiome will be measure using a single stool/faecal sample at four time points: baseline (0 weeks), following first intervention (4-6 weeks), following washout (7-9 weeks), and following the second intervention (11-15 weeks). |