The Effect of Probiotic Supplementation on Mental Health in Healthy Volunteers

Healthy Clinical Trial

— ProBeMent  

Official title:

The Effect of Supplementation With Lactobacillus Helveticus R0052 and Bifidobacterium Longum R0175 Combination Probiotic on Mental Health Indices and Oral Microbiota Status in Healthy Volunteers Facing a Stressful Event

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06391216
• Other study ID #: ProBeMent
• Status: Active, not recruiting
• Phase: N/A
• Start date: May 6, 2024
• Est. completion date: July 5, 2024

Study information

• Verified date: May 2024
• Source: Medical University of Lodz
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Probiotics are "live microorganisms which when administered in adequate amounts confer a health benefit on the host". Accumulating evidence indicates their effect in mental health restoration. Beneficial neuropsychological and psychobiological effects are particularly well substantiated in clinical samples. However, it is not clearly documented whether probiotic supplementation reduces depressive and anxiety symptoms in healthy volunteers experiencing temporal deterioration in mental functioning while facing a stressful event. The combination of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 is particularly well studied in terms of its central nervous system action with significantly deciphered mechanism. As a result, this combination is particularly promising to study the effect of mental health improvement in healthy volunteers facing a stressful event.

The aim of this project is to assess the impact of a 8-week supplementation with probiotic combination of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 strains in the daily dose of 3 × 10^9 colony forming units on mental health measures and oral microbiota composition and metabolome in healthy young adults facing a psychologically stressful event. The aim will be achieved by comparing the probiotic combination supplement to placebo in a randomized triple-blind controlled trial settings with a participant allocation ratio of 1:1.

The summer academic examination session and the upcoming first take of the final exam in pharmacology at third year of medical studies will be a model of a stressful event. The participants will supplement their diets with probiotic/placebo for 8 weeks before the exam. After giving written informed consent, before the supplementation (relatively stress-free time period in terms of academic activities) the participants will provide background sociodemographic, anthropometric and psychometric data. At that time, participants will also give samples of saliva to assess cortisol and selected cytokines concentrations as well as salivary microbiome and metabolome. At the end of supplementation, a day before the final exam, participants will donate salivary samples and do psychometric tests for the second time to assess the same parameters as at the beginning of the study. Participants will also do a pre-exam test in pharmacology (not considered a formal academic assessment) as a comparator for the results of the formal examination held a day after.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 100
• Est. completion date: July 5, 2024
• Est. primary completion date: July 5, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 30 Years

Eligibility

Inclusion Criteria:

• status of a third-year medical student at the Faculty of Medicine of the Medical University of Lodz

• age (18-30 years)

• high motivation and no formal obstacles to sit the first take of the final exam in pharmacology

• Body mass index of 18-25 kg/m2

Exclusion Criteria:

• chronic dental diseases (in particular periodontal diseases), neurological, psychiatric, cardiological, gastroenterological, endocrinological, immunological, inflammatory or infectious diseases or disorders

• psychiatric or neurological diagnosis - within the last 1 year

• immune disorders or possible immunodeficiency - within the last 5 years

• previous bariatric surgery - within the last 5 years

• hospitalization - within the last 3 months

• presence of central venous catheters

• use of enteral nutrition (feeding tube or nutritional fistula)

• pregnant or planning to become pregnant in the next 3 months

• breast-feeding

• occurrence of an allergic reaction - within the last 3 months

• hypersensitivity to potato starch or magnesium stearate

• chronic use of any medicinal products - within the last 3 months

• use of systemic antibacterial or antifungal drugs - within the last 1 month

• alcohol abuse (= 20 g or = 40 g of alcohol per day for women and men, respectively) - within the last 3 months

• abuse of narcotic or psychotropic substances - within the last 3 months

• regular smoking of tobacco or other nicotine products, including e-cigarettes (> 5 cigarettes or equivalents per day - within the last 3 months)

• use of probiotic or prebiotic preparations - within the last 1 month

• a vegan diet or any unusual diet

Related Conditions & MeSH terms

• Anxiety
• Depression
• Healthy
• Stress-related Problem

Intervention

Dietary Supplement:
• Lactobacillus helveticus R0052 and Bifidobacterium longum R0175
8-week supplementation (56 days); 3 × 10^9 CFU/day
• Placebo
8-week supplementation (56 days)

Locations

Country	Name	City	State
Poland	Medical University of Lodz	Lódz

Sponsors (3)

Lead Sponsor	Collaborator
Medical University of Lodz	Pomeranian Medical University Szczecin, SANPROBI Sp. z o.o. Sp.k.

Country where clinical trial is conducted

Poland, 

References & Publications (5)

Ait-Belgnaoui A, Colom A, Braniste V, Ramalho L, Marrot A, Cartier C, Houdeau E, Theodorou V, Tompkins T. Probiotic gut effect prevents the chronic psychological stress-induced brain activity abnormality in mice. Neurogastroenterol Motil. 2014 Apr;26(4):510-20. doi: 10.1111/nmo.12295. Epub 2013 Dec 30. — View Citation

Ait-Belgnaoui A, Payard I, Rolland C, Harkat C, Braniste V, Theodorou V, Tompkins TA. Bifidobacterium longum and Lactobacillus helveticus Synergistically Suppress Stress-related Visceral Hypersensitivity Through Hypothalamic-Pituitary-Adrenal Axis Modulation. J Neurogastroenterol Motil. 2018 Jan 30;24(1):138-146. doi: 10.5056/jnm16167. — View Citation

Chao L, Liu C, Sutthawongwadee S, Li Y, Lv W, Chen W, Yu L, Zhou J, Guo A, Li Z, Guo S. Effects of Probiotics on Depressive or Anxiety Variables in Healthy Participants Under Stress Conditions or With a Depressive or Anxiety Diagnosis: A Meta-Analysis of Randomized Controlled Trials. Front Neurol. 2020 May 22;11:421. doi: 10.3389/fneur.2020.00421. eCollection 2020. — View Citation

Karbownik MS, Kreczynska J, Kwarta P, Cybula M, Wiktorowska-Owczarek A, Kowalczyk E, Pietras T, Szemraj J. Effect of Supplementation with Saccharomyces Boulardii on Academic Examination Performance and Related Stress in Healthy Medical Students: A Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients. 2020 May 19;12(5):1469. doi: 10.3390/nu12051469. — View Citation

Messaoudi M, Lalonde R, Violle N, Javelot H, Desor D, Nejdi A, Bisson JF, Rougeot C, Pichelin M, Cazaubiel M, Cazaubiel JM. Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. Br J Nutr. 2011 Mar;105(5):755-64. doi: 10.1017/S0007114510004319. Epub 2010 Oct 26. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cortisol	Salivary cortisol level measured with ELISA test	Day 0, Day 55
Primary	Depression symptoms under examination-related stress	Depression symptoms measured with Depression Anxiety Stress Scale - 21 (DASS-21). Seven items, each scored 0 to 3 points, yielding a total between 0 and 21 points. The more points the more severe depression.	Day 0, Day 55
Primary	Anxiety symptoms under examination-related stress	Anxiety symptoms measured with Depression Anxiety Stress Scale - 21 (DASS-21). Seven items, each scored 0 to 3 points, yielding a total between 0 and 21 points. The more points the more severe anxiety.	Day 0, Day 55
Primary	Stress symptoms under examination-related stress	Stress symptoms measured with Depression Anxiety Stress Scale - 21 (DASS-21). Seven items, each scored 0 to 3 points, yielding a total between 0 and 21 points. The more points the more severe stress.	Day 0, Day 55
Primary	Performance under examination-related stress	Number of correctly-answered questions in the final examination in pharmacology in relation to subject knowledge assessed in the pre-exam test. 60 questions, each scored 0 or 1 point, yielding a total between 0 and 60 points. The more points the better performance under examination-related stress.	Day 56
Secondary	Interleukin-1ß (IL-1ß)	Salivary IL-1ß level measured with ELISA test in relation to total protein concentration in saliva	Day 0, Day 55
Secondary	Interleukin-8 (IL-8)	Salivary IL-8 level measured with ELISA test in relation to total protein concentration in saliva	Day 0, Day 55
Secondary	Microbiome	Salivary microbiome assessed with 16S rRNA gene sequencing	Day 0, Day 55
Secondary	Metabolome	Salivary metabolome assessed with liquid chromatography-mass spectrometry	Day 0, Day 55
Secondary	Mood	Current mood measured with a pictogram-enhanced visual analog mood scale. A single item scored 0 to 10 points, yielding a total between 0 and 10 points. The more points the better mood.	Day 0, Day 55
Secondary	Depression symptoms under examination-related stress (supportive measure)	Depression symptoms measured with Patient Health Questionnaire - 9 (PHQ-9). Nine items, each scored 0 to 3 points, yielding a total between 0 and 27 points. The more points the more severe depression.	Day 0, Day 55
Secondary	Anxiety symptoms under examination-related stress (supportive measure)	Anxiety symptoms measured with General Anxiety Disorder - 7 (GAD-7). Seven items, each scored 0 to 3 points, yielding a total between 0 and 21 points. The more points the more severe anxiety.	Day 0, Day 55
Secondary	Sleep quality under examination-related stress	Sleep quality status measured with Pittsburgh Sleep Quality Index (PSQI). Seven components, each scored 0 to 3 points, yielding a total composite score of 0 to 21 points. The more points the more sleep difficulties.	Day 0, Day 55
Secondary	Fatigue under examination-related stress	Fatigue status measured with Fatigue Severity Scale (FSS). Nine items, each scored 1 to 7 points, yielding a total between 7 and 63 points. The more points the greater fatigue severity.	Day 0, Day 55