Stress-buffering and Sleep Disturbance-resilient Effects of a Dual Bifidobacterium Longum Combination Under Short-term Travel

Stress-buffering and Sleep Disturbance-resilient Effects of a Dual Bifidobacterium Longum Combination Under Short-term Travel: A Randomized, Double-blind, Placebo-controlled Study

This study aims to evaluate the effects of a dual Bifidobacterium longum probiotic formulation (dipro-O and dipro-X) on sleep quality, stress responses, and gut microbiota stability in healthy adults during short-term travel. Using a randomized, double-blind, placebo-controlled design, the study investigates whether probiotic supplementation can enhance sleep resilience, buffer stress, and modulate microbiome and physiological responses under travel-related environmental changes.

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Probiotic

Detailed Description

With increasing global mobility, short-term travel has become a common aspect of modern life. However, rapid environmental transitions, including changes in time zones, diet, daily routines, and psychosocial stress, can disrupt physiological homeostasis. Among the most affected systems are sleep regulation, stress responses, and gut microbiota composition. Travel-related circadian misalignment and psychological stress are known to impair sleep quality, while dietary shifts and environmental exposure can alter gut microbial balance, potentially leading to gastrointestinal discomfort, immune dysregulation, and reduced overall well-being.

Emerging evidence highlights the central role of the gut-brain axis in mediating interactions between microbiota, stress, and sleep. Alterations in gut microbiota can influence neuroendocrine pathways, including the hypothalamic-pituitary-adrenal (HPA) axis, as well as neurotransmitter systems involved in sleep and mood regulation. Consequently, maintaining microbiota stability during periods of acute stress, such as travel, may be critical for preserving both physiological and psychological resilience.

Probiotics have gained increasing attention as a potential strategy to support health under such conditions. Defined as live microorganisms that confer health benefits when administered in adequate amounts, probiotics, particularly strains within the Bifidobacterium genus, have been shown to modulate gut microbiota composition, enhance barrier function, regulate immune responses, and influence neuroendocrine signaling. Certain Bifidobacterium longum strains have demonstrated beneficial effects on stress reduction, sleep quality, and emotional regulation, suggesting their potential role in mitigating travel-related disturbances.

In this study, a dual-strain formulation containing Bifidobacterium longum subsp. longum dipro-O and dipro-X is employed, selected for their potential synergistic effects on microbiota modulation and stress resilience. These strains are hypothesized to support gut microbial stability, regulate stress-related biomarkers such as cortisol and salivary α-amylase, and improve sleep-related outcomes through modulation of neuroendocrine and microbial pathways.

To comprehensively evaluate these effects, the study integrates clinical, physiological, and multi-omics approaches. Sleep quality is assessed using both subjective (PSQI) and objective (wearable-derived) measures, while psychological status is evaluated using validated questionnaires (DASS-42, WHO-5). Biological samples, including saliva and feces, are collected to assess stress biomarkers, immune and inflammatory markers, and gut microbiota composition and function using metagenomic sequencing.

Importantly, the study adopts a longitudinal design encompassing pre-travel, travel, and post-travel phases, allowing for the assessment of dynamic changes and recovery patterns. This approach enables evaluation of not only the immediate effects of probiotic supplementation but also its potential to enhance resilience and facilitate recovery following environmental stress.

Overall, this study aims to provide mechanistic and clinical evidence supporting the use of targeted probiotic interventions as a strategy to improve sleep quality, buffer stress responses, and maintain microbiota homeostasis during short-term travel. By integrating microbiome, physiological, and psychological data, the findings are expected to contribute to the development of personalized, mechanism-based approaches for promoting health and resilience in the context of modern travel.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jie Yuan, M.Sc.; Email: peanut.yuan@diprobio.com
• Study Contact Backup: Name: Daisy Zhao, Ph.D.; Phone Number: 3400 8680; Email: daisydy.zhao@polyu.edu.hk

Study Locations

• Hong Kong
  • Kowloon
    • Kowloon, Kowloon, Hong Kong
      • The Hong Kong Polytechnic University
      • Contact: Jie Yuan, M.Sc.; Email: peanut.yuan@diprobio.com
      • Contact: Daisy Zhao, Ph.D.; Phone Number: 3400 8680; Email: daisydy.zhao@polyu.edu.hk
      • Principal Investigator: Daisy Zhao, Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Willing to participate in this study and able to provide written informed consent before any study procedures are initiated.
• Able and willing to comply with all study procedures as required by the protocol, including continuous wearable device use, saliva and stool sample collection, and completion of questionnaire assessments.
• Willing to accept randomization and group allocation as determined by the study protocol.

Exclusion Criteria:

• Known use of antibiotics or systemic corticosteroids within 4 weeks prior to enrollment.
• Use of probiotic supplements within 4 weeks prior to enrollment.
• Planned use of any probiotic supplements during the study period.
• Known history or current presence of major endocrine disorders, active inflammatory bowel disease or other severe gastrointestinal diseases, or severe sleep disorders requiring treatment adjustment.
• Pregnant or intend to get pregnant, or lactating women.
• Known allergy to any probiotic products.
• Participation in any other clinical interventional study involving drugs, dietary supplements, probiotics, or prebiotics within the past three months.
• Or those who, according to the researcher's judgment, may have inadequate adherence or are unable to complete the study protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Daily one sachet containing maltodextrin	Dietary supplement: Placebo; Daily one sachet containing maltodextrin
Active Comparator: Probiotic; Daily one sachet containing Bifidobacterium longum subsp. longum dipro-O and Bifidobacterium longum subsp. longum dipro-X, with a combined total dose of 5 × 10⁹colony-forming units (CFU) and maltodextrin as carrier	Dietary supplement: Probiotic; Daily one sachet containing Bifidobacterium longum subsp. longum dipro-O and Bifidobacterium longum subsp. longum dipro-X, with a combined total dose of 5 × 10⁹colony-forming units (CFU) and maltodextrin as carrier

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sleep quality during short-term travel following probiotic intervention compared with placebo as assessed via questionnaire	Changes in sleep quality from generally healthy adults during short-term travel following probiotic intervention compared with placebo, via the Pittsburgh Sleep Quality Index (PSQI) questionnaire, scale 0-3 where higher scores indicate poorer sleep quality.	10-days
Sleep quality during short-term travel following probiotic intervention compared with placebo as assessed using wearable device monitoring.	Changes in sleep- and cardiac-related physiological parameters from generally healthy adults during short-term travel following probiotic intervention compared with placebo as assessed using the Huawei Band 10 NFC edition.	10-days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
General well being in generally healthy adults upon administration of probiotic or placebo as assessed using questionnaire	Differences in general well being using the World Health Organization Five Well-Being Index (WHO-5), having a scale of 0-5 where higher scores indicate better well being, upon administration of probiotic compared to placebo.	10-days
Psychological well being in generally healthy adults upon administration of probiotic or placebo as assessed using questionnaire	Differences in psychological well being using the Depression, Anxiety and Stress Scale - 42 items (DASS-42), having a scale of 0-3 where higher scores indicate more severe depression, anxiety, or stress symptoms, upon administration of probiotic compared to placebo.	10-days
Microbiota profiles of fecal samples in generally healthy adults upon administration of probiotic or placebo as assessed via metagenomics sequencing.	Differences in microbiota abundance in fecal sample of generally healthy adults upon administration of probiotic compared to placebo.	10-days
Gastrointestinal immune biomarkers in generally healthy adults upon administration of probiotic or placebo as assessed using Enzyme-Linked Immunosorbent Assay (ELISA)	Differences in concentrations of gastrointestinal immune biomarkers upon administration of probiotic compared to placebo such as calprotectin using Enzyme-Linked Immunosorbent Assay (ELISA)	10-days
Salivary stress biomarkers in generally healthy adults upon administration of probiotic or placebo as assessed using Enzyme-Linked Immunosorbent Assay (ELISA)	Differences in concentrations of salivary stress biomarkers upon administration of probiotic compared to placebo such as cortisol using Enzyme-Linked Immunosorbent Assay (ELISA)	10-days

Collaborators and Investigators

• Sponsor: Min-Tze LIONG
• Collaborators: The Hong Kong Polytechnic University

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: March 30, 2026
• First Submitted That Met QC Criteria: March 30, 2026
• First Posted (Actual): April 6, 2026

Study Record Updates

• Last Update Posted (Actual): April 6, 2026
• Last Update Submitted That Met QC Criteria: March 30, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: sleep; probiotic; gut microbiota; Bifidobacterium; short term travel
• Additional Relevant MeSH Terms: Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Probiotics
• Other Study ID Numbers: HKPU-230326

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