Adolescent Probiotics in Stressed Adolescents

April 29, 2026 updated by: Elena Enioutina, University of Utah

Analysis of Brain and Immune Functions in Adolescents Using Probiotics

Stress is a normal human reaction to changes surrounding our reality, resulting in physical, emotional, and intellectual responses. Children and adolescents often experience high levels of stress. Age and gender may affect a child's ability to manage stress. Children and adolescents experiencing stress could be at an increased risk of poor cognitive, social, and emotional functioning. Probiotics are living microorganisms that could positively affect microbiota, support functions of numerous organs and systems, and overall human health. Most probiotics belong to the Lactobacillus genus. Probiotics can potentially support mental health, psychological function, and immune defenses.

The purpose of this exploratory clinical trial is to investigate whether supplementation of the diets of adolescents experiencing moderate stress with the probiotic dietary supplement a blend of two probiotic Lactobacillus plantarum and one Lactobacillus brevis strains will support their emotions (e.g., psychological well-being, social relationship, stress levels, and self-efficacy), cognitive (e.g., attention, episodic and working memory) and immune functions (e.g., salivary IgA and salivary cytokine productions). This study is intended only to evaluate the dietary supplement's effect on the body's structure or function. Our investigation is not intended to mitigate, cure, treat, or prevent disease.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Children and adolescents often experience high levels of stress. Age and gender may affect the ability of a child to manage stress. Children and adolescents experiencing stress could be at an increased risk of poor cognitive, social, and emotional functioning, and may have altered immune responses due to stress.

Probiotics are living microorganisms that could positively affect microbiota, support functions of numerous organs and systems, and overall human health. Most probiotics belong to the Lactobacillus genus. It has been suggested that probiotics potentially can support mental health, psychological function, and immune defenses. Recent studies confirmed that the use of pre- and probiotics improves the psychological scores of people predisposed to mood disorders. A supplementation of the diet of healthy volunteers with a probiotic for four weeks resulted in a significant reduction of subjects' rumination and aggressive thoughts. Lactobacillus plantarum DR7 reduces signs of stress and improves immune functions in adults. Consumption of this probiotic for 12 weeks reduced signs of stress and improved the psychological scores of participants. The levels of inflammatory cytokines are higher in people with anxiety. The use of Lactobacillus plantarum DR7 reduced levels of inflammatory cytokines (e.g., IFNgamma).

The purpose of this exploratory clinical trial is to investigate whether supplementation of the diets of adolescents experiencing moderate stress with the probiotic dietary supplement a blend of two Lactobacillus plantarum and one Lactobacillus brevis probiotic strains will support participants emotions (e.g., psychological well-being, social relationship, stress levels, and self-efficacy), cognitive (e.g., attention, episodic and working memory) and immune functions (e.g., salivary IgA and salivary cytokine productions). This study is intended only to evaluate the dietary supplement's effect on the body's structure or function. Our investigation is not intended to mitigate, cure, treat, or prevent disease.

The study will be an exploratory single-blind, randomized clinical trial of a dietary supplement containing 2 billion CFU of a probiotic strains: two Lactobacillus plantarum and one Lactobacillus brevis probiotic strains. Stains are present in the mixture at a ratio of 2:1:1. All strains are currently used as dietary supplements in the United States.

Participants for this trial will be selected based on the following criteria: participants age 12-20 years old, BMI percentile >5% and <97% with moderate stress levels (Perceived Stress Scale (PPS) score 14-26), receiving or not receiving cognitive behavioral therapy, and not on selective serotonin reuptake inhibitors (SSRIs). Investigators planned to enroll 120 participants, with 60 participants in the dietary supplement (Probiotics) arm. The probiotics arm will receive caps with the probiotic blend, and control participants will receive caps containing a placebo for the same period. Participants will be asked to consume the caps with dinner meals for 12 consecutive weeks. If the probiotic was not taken during dinner, then it should be taken within 2 hours after dinner or with the next meal.

The investigators have used the NIH Toolbox for Assessment of Neurological and Behavioral Function, which has been designed for scientists interested in evaluating the emotional and cognitive functions of clinical study participants. NIH Toolbox was validated across the entire age range.

The Investigators used the following NIH Toolbox domains to assess participants' progress:

  1. Emotion Domain consisting of instruments evaluating psychological well-being, social relationships, stress, self-efficacy, and negative affect. Additionally, we used PROMIS CAT Emotional Support, Psychological Stress Experiences, and Sleep Disturbance tests.
  2. Cognition Domain consisting of attention, episodic and working memories, language, and processing speed.

Biomarkers of immune function were investigated: salivary cytokine levels IL1beta, IL6, IL8, IFNgamma, and TNFα, and IL10, and immunoglobulin - secretory IgA.

4. Salivary AM and PM cortisol levels were measured All biomarkers were measured at baseline, 8 weeks, and 12 weeks of probiotics/placebo use by participants.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
104

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Utah
      • Salt Lake City, Utah, United States, 84108
        • Division Clinical Pharmacology, SOM, University of Utah
      • Salt Lake City, Utah, United States, 84108
        • University of Utah, Pediatrics and Primary Childrens Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. Participants: Males and females
  2. Participants: 12-20 years old
  3. Participants with sustained moderate stress levels as determined by the Perceived Stress Scale (PSS), average score 14-26
  4. Participants with BMI percentile >5% and <97%
  5. Participants receiving or not receiving cognitive behavioral therapy.

Exclusion Criteria:

  1. Participants less than 12 years of age or over 20 years of age at enrollment.
  2. Participants with PSS average scores less than 14 and more than 26.
  3. Participants with BMI percentile <5% or >97%
  4. Participants receiving selective serotonin reuptake inhibitors (SSRIs).
  5. Participants who take any nutraceutical having an effect on stress anxiety within 1 month before subject screening.
  6. Participants who are female and report being pregnant.
  7. Participants receiving immunosuppressive therapy.
  8. Participants having immune deficiencies.
  9. Adverse reactions to any probiotic.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Probiotics supplement
Participants received the probiotics blend containing two Lactobacillus plantarum and one Lactobacillus brevis strains for 12 weeks. The probiotic blend contained 2 billion CFU bacteria. Stains are present in the mixture at a ratio of 2:1:1. Participants were taking them daily with meals, (preferably with a dinner meal) for 12 consecutive weeks. If the probiotic was not taken during dinner, it should be taken within 2 hours after dinner or with the next meal
Dietary supplement: Probiotics
The participants started taking capsules the day after the first visit, after collecting the AM saliva sample, and continued taking them daily (preferably with a dinner meal) for 12 consecutive weeks. If the probiotic was not taken during dinner, it should be taken within 2 hours after dinner or with the next meal
Placebo Comparator: Placebo cohort
The participants started taking placebo capsules the day after the first visit, after collecting the AM saliva sample, and continued taking them daily (preferably with a dinner meal) for 12 consecutive weeks. If the capsule was not taken during dinner, it should be taken within 2 hours after dinner or with the next meal
Dietary supplement: placebo
The participants started taking placebo capsules the day after the first visit, after collecting the AM saliva sample, and continued taking them daily (preferably with a dinner meal) for 12 consecutive weeks. If the probiotic was not taken during dinner, it should be taken within 2 hours after dinner or with the next meal

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Emotinal status and cognitive functions of participants
Time Frame: From enrollment (week 0), 8 weeks and 12 weeks (end of study)
The NIH Toolbox was used to assess participants' emotional and cognitive functions. The Emotion Domain consisted of instruments evaluating psychological well-being, social relationships, stress, self-efficacy, and negative affect. Additionally, PROMIS CAT Emotional Support, Psychological Stress Experiences, and Sleep Disturbance tests were administered. The Cognition Domain test consisted of attention, episodic and working memories, language, and processing speed.
From enrollment (week 0), 8 weeks and 12 weeks (end of study)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Changes in the immune functions of participants
Time Frame: From enrollment (week 0), 8 weeks and 12 weeks (end of study)

Biomarkers of immune function were analyzed.

  1. Salivary cytokine levels: IL1beta, IL6, IL8, IFNgamma, and TNFα, and Th2 (IL10) cytokines,
  2. Salivary immunoglobulin sIgA. Collected samples were stored in a -80°C freezer until shipped for analysis to Salimetrics. Saliva samples were analyzed in duplicates by Salimetrics.
From enrollment (week 0), 8 weeks and 12 weeks (end of study)
Evaluation of AM and PM cortisol levels
Time Frame: From enrollment (week 0), 8 weeks and 12 weeks (end of study)
Salivary samples for cortisol analysis were collected by participants 1-2 days before the in-person appointment and stored in the household freezers. AM samples were collected before 8 AM, and PM samples were collected 2 hours before bedtime. Levels of cortisol were analyzed by Salimetrics
From enrollment (week 0), 8 weeks and 12 weeks (end of study)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Utah

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Kaneka Americas Holding Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

  • 1. Steenbergen, L., Sellaro, R., van Hemert, S., Bosch, J. A., and Colzato, L. S. (2015) A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood. Brain Behav Immun 48, 258-264 2. Chong, H. X., Yusoff, N. A. A., Hor, Y. Y., Lew, L. C., Jaafar, M. H., Choi, S. B., Yusoff, M. S. B., Wahid, N., Abdullah, M., Zakaria, N., Ong, K. L., Park, Y. H., and Liong, M. T. (2019) Lactobacillus plantarum DR7 alleviates stress and anxiety in adults: a randomised, double-blind, placebo-controlled study. Benef Microbes 10, 355-373 3. Quagliato, L. A., and Nardi, A. E. (2018) Cytokine alterations in panic disorder: A systematic review. J Affect Disord 228, 91-96

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 3, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 22, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 25, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 15, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 29, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 4, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 4, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 29, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 20211028

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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