Effects of Probiotics on Mood

Study Overview
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Brief Summary
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Recent demonstration that probiotics administration has positive effects on depressive feelings in healthy populations suggests its possible role as an adjuvant therapy for depression in clinical populations and as a non-invasive strategy to prevent depressive feelings in healthy individuals. The present study extends current knowledge on the beneficial effects of probiotics on psychological well-being, as measured by changes in mood (e.g., depression, anxiety, cognitive reactivity to sad mood), personality dimensions, and quality of sleep, which have been considered as related to mood. For this double-blind, placebo-controlled study healthy volunteers pseudo-randomly assigned to an experimental or control group assumed a daily dose of probiotic or placebo, respectively, for 6 weeks. Mood, personality dimensions, and sleep quality were assessed four times (before the beginning of the study, at 3 and 6 weeks, and at 3 weeks of washout).

Detailed Description
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A. THEORETICAL BACKGROUND The intestine and the brain are intimately connected with each other through the gut-brain axis, which involves bidirectional communication between the nervous, endocrine and immune systems. In the last years, it has become increasingly evident that this communication implies also interactions with the intestinal bacterial flora, which releases immune activation and other signalling molecules that may play a major role in the regulation of the brain and human behaviour. For instance, the microbiota produces neuroactive substances and their precursors (e.g. tryptophan) that may reach the brain through the endocrine and autonomous nervous system. Recently, the interest has been focused also on the cognitive field. Indeed, there is experimental evidence that bacterial products may positively influence cognitive functions, such as spatial memory and problem-solving abilities. Moreover, probiotics seem to exercise influence on mood, anxiety and depression, opening new therapeutic prospects. A recent trial showed that four weeks of taking probiotics (Bifidobacterium bifidum W23, Bifidobacterium lactis W52, Lactobacillus acidophilus W37, Lactobacillus brevis W63, Lactobacillus casei W56, Lactobacillus salivarius W24, Lactococcus lactis W19 e W58) led to an improvement in mood, fostering reduction in negative thoughts. B. THE PURPOSE OF THE RESEARCH PROJECT The primary goal of the trial is to investigate the effect of probiotics on depression. Moreover, it will assess also effects on anxiety and other personality traits in healthy young students. The trial intends also to investigate whether probiotics may influence the quality of sleep and bowel habits. The trial will be placebo-controlled, randomized, pre- and post-intervention, double-blind designed (investigator and participants). In the light of the several end-points examined, the statistical analysis will be of explorative type. The collection of faecal samples will allow, in case of finding any effects of the administered product on mood, to go back to any microbial components that have changed in individuals following the treatment. Monitoring (see below) the normal feed and physical habits of the individuals will allow to check the possible effect of these confounding factors on the parameters measured in the trial.

Official Title
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Randomized Controlled Experimental Trial Designed to Test the Effects of Probiotics on Mood

Conditions
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Depression, Anxiety

Intervention / Treatment
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* Dietary Supplement: Bifihappy
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and Famale subjects. Aged between 18 and 35. Already owing a smartphone with Android or iOS system. Exclusion Criteria: Drug taking, smoking, coeliac disease, lactose intolerance. Disorders such as IBS (Irritable Bowel Syndrome), IBD (Irritable Bowel Disease), UC (Ulcerative Colitis) and other serious diseases, e.g. MS (Multiple Sclerosis) and diabetes (type 1/type 2). Oral intake of antibiotics and other medicines on a continuative basis.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The trial design is parallel, with two groups (experimental group and control group) and four evaluation sessions at intervals of three weeks (T0wk = baseline, T3wk = intermediate, T6wk=final and T9wk = follow-up).
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>the subjects are treated with probiotics: Bifihappy | Dietary Supplement: Bifihappy<br>* During the six weeks of treatment, the experimental group will take daily doses of 2,5 g with a concentration of 4x109 CFU/sachet of a mixture of lyophilised probiotic strains of the following species: Lactobacillus fermentum Lactobacillus rhamnosus Lactobacillus plantarum Bifidobacterium longum<br>|
| Placebo Comparator: Group 2<br>the subjects are treated with a placebo | Other: Placebo<br>* During the six weeks of treatment, the experimental group will take daily doses of 2,5 g of maltodextrin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the psychological profile | The primary outcome is the difference in the scores at the Leiden Index of Depression Sensitivity-Revised test (LEIDS-R) standardized questionnaire between the experimental and control groups. The Leiden Index of Depression Sensitivity-Revised test, LEIDS-R, is a self-report questionnaire that tests cognitive reactivity to sad mood, which is an index of cognitive vulnerability to depression. | four evaluation sessions at intervals of three weeks of probiotic intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of mood - State Trait Anxiety Inventory (STAI) standardized questionnarie. | difference in the scores between the experimental and control groups. The State Trait Anxiety Inventory, STAI, is a self-report questionnaire that measures the presence and severity of current symptoms of anxiety and the propensity to be anxious. | four evaluation sessions at intervals of three weeks of probiotic intervention | 
| Evaluation of mood - Beck Depression Inventory (BDI-2) standardized questionnarie. | difference in the scores between the experimental and control groups. The Beck Depression Inventory, BDI-2, is a self-report questionnaire that measures the occurrence and severity of current depressive symptoms. | four evaluation sessions at intervals of three weeks of probiotic intervention | 
| Evaluation of mood - Profile od Mood State (POMS) standardized questionnarie. | difference in the scores between the experimental and control groups. The Profile of Mood State, POMS, is a self-report questionnaire that assesses mood. | four evaluation sessions at intervals of three weeks of probiotic intervention | 
| Evaluation of the quality of sleep. | difference in the scores between the experimental and control groups in the standardized questionnaire Pittsburgh Sleep Quality Index (PSQI). The Pittsburgh Sleep Quality Index, PSQI, is a self-report questionnaire that assesses sleep quality for the majority of days and nights in the past months. | four evaluation sessions at intervals of three weeks of probiotic intervention | 
| Evaluation of personality - Temperament and Character Inventory (TCI) standardized questionnarie. | difference in the scores between the experimental and control groups. The Temperament and Character Inventory, TCI, is a self-report, true-false questionnaire that measures two components of personality: temperament and character. | four evaluation sessions at intervals of three weeks of probiotic intervention | 
| Evaluation of personality - Cope Orientation to Problem Experienced-New Italian Version (COPE-NIV) standardized questionnarie. | difference in the scores between the experimental and control groups. The Cope Orientation to Problem Experienced - New Italian Version, COPE-NIV, is a self-report questionnaire that measures coping strategies: the cognitive and behavioral strategies people use to manage stressful situations. | four evaluation sessions at intervals of three weeks of probiotic intervention | 
| Evaluation of personality - Behavioral Inhibition System and Behavioral Activation System Scale (BIS/BAS) standardized questionnarie. | difference in the scores between the experimental and control groups. The Behavioral Inhibition and Behavioral Activation Scale, BIS/BAS, is a self-report questionnaire that measures an individual's sensitivity to behavioral inhibition and behavioral activation systems. | four evaluation sessions at intervals of three weeks of probiotic intervention | 
| Evaluation of personality - Life Orientation Test-revisited (LOT-R) standardized questionnarie. | difference in the scores between the experimental and control groups. The Life Orientation Test-revisited, LOT-R, is a self-report measure of dispositional optimism and pessimism. | four evaluation sessions at intervals of three weeks of probiotic intervention |