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.

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.

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.