Effect of Encapsulated vs Free Probiotic on Brain Function

Study Overview
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Brief Summary
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Aging is associated with changes in a wide variety of brain networks, including the default mode, saliency attention, and visual networks. Furthermore, current research suggests that a relationship exists between functional connectivity at rest and cognition. Lactocaseibacillus rhamnosus is an ideal strain for the intervention, as it has been show to affect the gut-brain axis, brain function, and behavior. Therefore, the investigators plan to assess resting state functional magnetic resonance imaging (fMRI) to compare changes in brain connectivity between the groups receiving the encapsulate and non-encapsulated Lactocaseibacillus rhamnosus supplements.

Official Title
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Comparing the Efficacy of Micro-encapsulated Lactocaseibacillus Rhamnosus vs Free Probiotic in Powder to Affect Brain Connectivity

Conditions
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Aging

Intervention / Treatment
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* Dietary Supplement: Maltodextrin
* Dietary Supplement: Encapsulated Lactocaseibacillus rhamnosus
* Dietary Supplement: Non-encapsulated Lactocaseibacillus rhamnosus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent prior to any study-related procedure Age 60-80 years-old Normal weight at the screening defined as BMI range 18.5-31.9 Willing to abstain from regular consumption of probiotic supplements or food products containing probiotic bacteria (including fermented food and beverages) Willing to abstain from regular consumption of supplements and medications known to alter gastrointestinal function or inflammatory status during the study Exclusion Criteria: Diagnosis of type 1 and/or type 2 diabetes Current (or within the last 4 weeks prior to study start) use of probiotic supplementation Immobile (defined as the inability to participate in all study-related procedures) History of complicated gastrointestinal surgery Diagnosed inflammatory bowel disease (IBD) Current diagnosis of psychiatric disease/s or syndromes Current diagnosis of neurodegenerative disease Systemic use of antibiotics and/or steroid medication in the last 4 months prior to inclusion Use of any non-steroidal anti-inflammatory drug (NSAID) more than 3 times a week for the last 2 months Consumption of any NSAID within 7 days of study start Any condition which could substantially interfere with intestinal barrier function (e.g. gluten sensitivity, lactose intolerance, celiac disease, irritable bowel syndrome (IBS), IBD) or in any other way with the outcome of the study, as decided by the principle investigator's discretion Regular smoking, use of snuff, nicotine, cannabidiol narcotics/supplements, or e-cigarette use Drinking more than 9 standard cups of alcohol per week and/or more than 3 standard cups of alcohol per occasion Regular use, for more than three times a week for the last 2 months and/or 7 days prior to inclusion, of medications which according to the principal investigator can have an anti-inflammatory effect or affect in any way the intestinal barrier function or have an impact on the study analysis (such as laxatives, anti-diarrheal, anti-cholinergic, etc.) After being included in the study, starting any medication or treatment that could potentially influence the study participation and/or study analysis Cerebral bleeding or history of cerebral bleeding Claustrophobia In operated apparatus (e.g., pacemaker), as it interferes with MR imaging Aneurysm clips in the head Shunts in the head Grenade-splinter or metal-splinter in the body (e.g., eyes) Metal or electrodes in the body (e.g., temp-catheter, aorta stent, cochlear implant) Comprehensive tooth-implants or prosthesis Operated in the head Operated in the heart Swallowed a video-capsule, which may still be in the GI tract Left-handed

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 80 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Encapsulated probiotic<br> | Dietary Supplement: Encapsulated Lactocaseibacillus rhamnosus<br>* Probiotic product<br>|
| Active Comparator: Non-encapsulated probiotic<br> | Dietary Supplement: Non-encapsulated Lactocaseibacillus rhamnosus<br>* Probiotic product<br>|
| Placebo Comparator: Placebo<br> | Dietary Supplement: Maltodextrin<br>* Placebo product<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain functional connectivity as measured by resting-state functional magnetic resonance imaging (fMRI) | corrected for baseline | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Levels of inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the brain using MR spectroscopy (MRS) | corrected for baseline | 6 weeks | 
| Cognitive function assessment using the trail making test (TMT) | corrected for baseline, scale 0-400 seconds and number of errors, higher scores indicate worse cognition | 6 weeks | 
| Cognitive function assessment using digit symbol substitution test (TMT) | corrected for baseline, scale 0-93 points, higher scores indicate better cognition | 6 weeks | 
| Cognitive function assessment using letter digit substitution test | corrected for baseline, scale 0-135 points, higher scores indicate better cognition | 6 weeks | 
| Cognitive function assessment using letter comparison test | corrected for baseline, scale 0-42 points, higher scores indicate better cognition | 6 weeks | 
| Cognitive function assessment using Rey-Auditory Verbal Learning Test | corrected for baseline, scale 0-120 points, higher scores indicate better cognition | 6 weeks | 
| Cognitive function assessment using N-back task | corrected for baseline, higher scores indicate better cognition | 6 weeks | 
| Cognitive function assessment using Face-Name Paired Associate Task (FNPA) | corrected for baseline, higher scores indicate better cognition | 6 weeks | 
| Levels of inflammatory markers (e.g. high sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, tumor necrosis factor (TNF)-alpha) | corrected for baseline, unit of measurement concentration given as mg/ml | 6 weeks | 
| Levels of inflammatory markers (e.g. high sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, tumor necrosis factor (TNF)-alpha) | corrected for baseline, unit of measurement concentration given as mg/ml | 3 weeks | 
| Levels of metabolic blood markers (blood fats) | corrected for baseline, unit of measurement concentration given as mg/ml | 6 weeks | 
| Levels of metabolic blood markers (blood fats) | corrected for baseline, unit of measurement concentration given as mg/ml | 3 weeks | 
| Levels of neural blood markers (brain derived neurotrophic factor (BDNF), serotonin) | corrected for baseline, unit of measurement concentration given as mg/ml | 6 weeks | 
| Levels of neural blood markers (brain derived neurotrophic factor (BDNF), serotonin) | corrected for baseline, unit of measurement concentration given as mg/ml | 3 weeks | 
| Characterisation of lymphocyte subpopulations using flow cytometry | corrected for baseline | 6 weeks | 
| Faecal samples for evaluation of gut microbiota composition via next-generation sequencing (NGS) | corrected for baseline | 6 weeks |