The Effects of Probiotic Supplementation on State and Trait Stress, Anxiety, and Depression Symptoms in Stressed Adults

Evaluating the Effects of Lactobacillus Reuteri DSM 17938 on State and Trait Stress in Stressed Adults

The goal of this randomized controlled trial is to learn if supplementation with the probiotic Lactobacillus reuteri DSM 17938 can reduce levels of trait and state perceived stress, anxiety, and depressive symptoms compared to a placebo in a population of stressed adults ages 18-45. This study also investigates several evidence-based moderators of treatment effects, evaluates whether the probiotic caused side effects, and evaluates whether effects endured at 1-month post-supplementation.

Study Overview

• Status: Completed
• Conditions: Depressive Symptoms; Anxiety Symptoms; Perceived Stress
• Intervention / Treatment: Dietary supplement: Lactobacillus reuteri DSM 17938; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Boulder, Colorado, United States, 80309
      • University of Colorado Boulder, Muenzinger Psychology Building

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• age 18 - 45
• scoring 14+ on the perceived stress scale-10 indicating medium stress or higher
• ability to provide informed consent
• willingness not to take probiotic supplements (pills, tablets, oils, etc.) other than the product provided in the clinical study until all study procedures are completed
• own a smartphone and are willing to receive study materials and complete study procedures by text

Exclusion Criteria:

• a history of gastrointestinal discomfort or surgery, urinary incontinence, cancer, toxic shock syndrome, frequent diarrhea, vital signs outside of the acceptable range (i.e., blood pressure >160/100, oral temperature >100°F, pulse >100), heart disease, heart attack, lung/respiratory disease, any pulmonary, cardiovascular, gastrointestinal, hepatic or renal functional abnormality (i.e. a medical diagnosis related to lungs, heart, stomach/intestines, liver, or kidneys), HIV, Hepatitis B, Hepatitis C, bipolar disorder, psychosis, or confirmed or suspected immunosuppression or immunodeficiency
• current (past month) alcohol or substance abuse or dependence (score of 2+ on the UNCOPE)
• consistent (e.g., 5x/week or greater) probiotic supplementation within the last month, including probiotic food products such as yogurt
• receiving antibiotics within the last month
• receiving medications that interfere with gut motility (opiates, loperamide, stool softeners)
• use of systemic antibiotics, antifungals, antivirals, or antiparasitics (intravenous, intramuscular, or oral)
• use of oral, intravenous, intramuscular, nasal or inhaled corticosteroids
• use of cytokines or cytokine inhibitors
• use of methotrexate or immunosuppressive cytotoxic agents
• receiving immunosuppressive drugs/medications or treatment including antineoplastic therapy, post-transplantation immunosuppressive therapy, and/or radiation therapy
• participation in conflicting interventional research protocol
• unstable dietary history as defined by major changes in diet during the previous month, where the subject has eliminated or significantly increased a major food group in their diet
• female who is pregnant or lactating or reports expecting to get pregnant during the course of the study
• currently involved in the criminal justice system as a prisoner or ward of the state

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Probiotic; 5 drops daily (100 million colony-forming units) for 46 days of Lactobacillus reuteri DSM 17938 in sunflower oil, medium chain triglyceride oil, and silicon dioxide.	Dietary supplement: Lactobacillus reuteri DSM 17938; 5 drops (100 million CFUs) daily for 46 days of L. reuteri DSM 17938 in sunflower oil, medium chain triglyceride oil, and silicon dioxide.
Placebo Comparator: Placebo; 5 drops daily for 46 days of a placebo consisting of the inactive ingredients from the probiotic supplement, specifically sunflower oil, medium chain triglyceride oil, and silicon dioxide.	Other: Placebo; 5 drops daily for 46 days of placebo consisting of inactive ingredients from probiotic supplement, specifically sunflower oil, medium chain triglyceride oil, and silicon dioxide.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in mean trait perceived stress as assessed by PSS-10	Perceived stress scale-10 (PSS-10) administered via REDCap. Possible score range of 0 to 40, with 0-13 considered low stress, 14-26 moderate stress, and 27-40 high stress.	Baseline and the end of treatment at 46 days
State perceived stress as assessed by adapted PSS-4 using ecological momentary assessment	Perceived stress scale-4 (PSS-4) administered via REDCap and adapted for state measurement. The investigators adapted this measure for state stress by asking participants to rate the intensity of perceived stress they were experiencing in the moment, as opposed to the frequency with which they experienced perceived stress over the past month. Possible score range of 0 to 16, with higher scores indicating higher levels of state stress.	Five times per day (hourly, 12-7pm, sent via text with a 15 minute response window) during the last 5 days of supplementation, days 42 to 46, when the investigators expect participants to have reached maximum benefit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in mean trait anxiety symptoms as assessed by GAD-7	Generalized Anxiety Disorder-7 scale (GAD-7) administered via REDCap. Possible score range of 0 to 21, with higher scores indicating higher levels of anxiety symptoms.	Baseline and the end of treatment at 46 days
Change from baseline in mean trait depressive symptoms as assessed by the PHQ-8	Patient Health Questionnaire-8 (PHQ-8) administered via REDCap. Possible score range of 0 to 24, with higher scores indicating higher levels of depression.	Baseline and the end of treatment at 46 days
State anxiety symptoms as assessed with the SUDS using ecological momentary assessment	Subjective units of distress scale (SUDS) administered via REDCap. Possible score range of 0 to 100, with higher scores indicating higher levels of state anxiety.	Five times per day (hourly, 12-7pm, sent via text with a 15 minute response window) during the last 5 days of supplementation, days 42 to 46, when the investigators expect participants to have reached maximum benefit
State depressive symptoms as assessed by SUDS using ecological momentary assessment	Subjective Units of Distress Scale (SUDS) administered via REDCap. Possible score range of 0 to 100, with higher scores indicating higher levels of state depression.	Five times per day (hourly, 12-7pm, sent via text with a 15 minute response window) during the last 5 days of supplementation, days 42 to 46, when the investigators expect participants to have reached maximum benefit

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Side effects as assessed on the final day of supplementation using the GASE	Generic Assessment of Side Effects (GASE), excluding the question assessing suicidality and administered on REDCap. This measure assesses 35 of the most common subjective side effects of clinical trials (e.g., nausea), and asks participants to rate whether they experienced each complaint on a scale from 0 ("not present") to 3 ("severe"). If they endorsed experiencing a side effect (score of 1+), participants were then asked whether the complaint related to the probiotic (yes/no).	End of treatment at day 46

Collaborators and Investigators

• Sponsor: University of Colorado, Boulder
• Investigators: Principal Investigator: Lauren B Finkelstein, MA, University of Colorado, Boulder

Publications and helpful links

Helpful Links

• Prior pre-registration on Open Science Framework, initially submitted prior to starting data collection

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2023
• Primary Completion (Actual): May 6, 2024
• Study Completion (Actual): June 1, 2024

Study Registration Dates

• First Submitted: October 10, 2025
• First Submitted That Met QC Criteria: October 10, 2025
• First Posted (Estimated): October 15, 2025

Study Record Updates

• Last Update Posted (Actual): November 18, 2025
• Last Update Submitted That Met QC Criteria: November 14, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Depression; Anxiety; Randomized controlled trial; Probiotic; Perceived stress; Lactobacillus reuteri DSM 17938
• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Behavior; Anxiety Disorders; Depression
• Other Study ID Numbers: 22-0234

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified individual participant data (IPD) will be shared with other researchers in our lab to conduct secondary analyses. Data sharing will ensure protection of participant confidentiality.
• IPD Sharing Time Frame: Beginning late summer/early fall of 2024 with no end date
• IPD Sharing Access Criteria: Faculty advisor who oversaw the initial trial is supervising another graduate student to use the data to address research questions outlined in the IRB-approved protocol, in addition to some secondary analyses.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No