Clinical trial NCT06391216: The Effect of Probiotic Supplementation on Mental Health in Healthy Volunteers
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Stress-related Problem
Depression
Anxiety
Keywords: Probiotics
Academic examination
Psychological stress
Depression
Anxiety
Lead sponsor: Medical University of Lodz
Sponsor class: OTHER
Collaborators: name: Pomeranian Medical University Szczecin
name: SANPROBI Sp. z o.o. Sp.k.
First posted: 2024-04-30
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Healthy medical students are assigned
Primary purpose: PREVENTION

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Cortisol
timeFrame: Day 0, Day 55
measure: Depression symptoms under examination-related stress
timeFrame: Day 0, Day 55
measure: Anxiety symptoms under examination-related stress
timeFrame: Day 0, Day 55
measure: Stress symptoms under examination-related stress
timeFrame: Day 0, Day 55
measure: Performance under examination-related stress
timeFrame: Day 56
Secondary outcomes:
measure: Interleukin-1β (IL-1β)
timeFrame: Day 0, Day 55
measure: Interleukin-8 (IL-8)
timeFrame: Day 0, Day 55
measure: Microbiome
timeFrame: Day 0, Day 55
measure: Metabolome
timeFrame: Day 0, Day 55
measure: Mood
timeFrame: Day 0, Day 55
measure: Depression symptoms under examination-related stress (supportive measure)
timeFrame: Day 0, Day 55
measure: Anxiety symptoms under examination-related stress (supportive measure)
timeFrame: Day 0, Day 55
measure: Sleep quality under examination-related stress
timeFrame: Day 0, Day 55
measure: Fatigue under examination-related stress
timeFrame: Day 0, Day 55
Other outcomes:
Locations:
city: Łódź
country: Poland
facility: Medical University of Lodz
Study officials:
affiliation: Medical University of Lodz
name: Michał S. Karbownik, PhD
role: STUDY_CHAIR
References:
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.
citation: 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.
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.
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.
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.