Efficacy and Safety of Encapsulated Bifidobacterium Longum BBH016 in Subjects With Lower Gastrointestinal Symptoms

Efficacy and Safety of Encapsulated Bifidobacterium Longum BBH016 Bacteria in Subjects With Lower Gastrointestinal Symptoms: a Prospective, Double-blinded, Randomized Controlled Clinical Trial

Functional lower gastrointestinal (GI) symptoms such as abdominal pain, diarrhea, loose stools, and bloating are common in adults without identifiable organic disease and are associated with impaired quality of life and increased healthcare utilization. Growing evidence suggests that alterations in the gut microbiota may contribute to the development of these symptoms, supporting the potential role of probiotics as a therapeutic strategy.

Bifidobacterium longum BBH016 is a probiotic strain isolated from a healthy donor and classified as Generally Recognized as Safe (GRAS). Preclinical studies have suggested that BBH016 may alleviate abdominal symptoms, reduce intestinal inflammation, and improve gut microbial balance.

This investigator-initiated, randomized, double-blind, placebo-controlled clinical trial aims to evaluate the efficacy and safety of BBH016 capsules in adults with functional lower GI symptoms excluding constipation-predominant presentations. The study will be conducted at Seoul National University Bundang Hospital.

A total of 88 participants aged 19-80 years will be randomized in a 1:1 ratio to receive either BBH016 capsules or placebo for 8 weeks (two capsules twice daily). Participants will be assessed at baseline, 4 weeks, and 8 weeks.

The primary endpoint is overall improvement in GI symptoms at week 8 compared with baseline between treatment groups. Secondary endpoints include changes in individual symptom scores, IBS Symptom Severity Score (IBS-SSS), IBS Quality of Life (IBS-QoL), stool frequency and form assessed by the Bristol Stool Form Scale, and psychological well-being measured using the Hospital Anxiety and Depression Scale (HADS). Stool samples will also be collected to evaluate changes in the gut microbiome and their association with clinical outcomes.

Study Overview

• Status: Active, not recruiting
• Conditions: Irritable Bowel Syndrome; Diarrhea; Lower Abdominal Pain
• Intervention / Treatment: Dietary supplement: Placebo Capsule(s); Dietary supplement: Bifidobacterium longum BBH016

Detailed Description

Functional lower gastrointestinal (GI) symptoms such as abdominal pain, diarrhea, loose stools, and bloating are common in adults without evidence of organic disease. Although these symptoms are not life-threatening, they substantially impair quality of life, contribute to repeated healthcare utilization, and impose socioeconomic burdens. Current management strategies rely primarily on dietary modifications and symptomatic medications, but these often provide incomplete relief. Increasing evidence indicates that alterations in the gut microbiota play a critical role in the pathophysiology of functional GI disorders, including irritable bowel syndrome (IBS), through effects on visceral sensitivity, motility, immune regulation, and the brain-gut axis. Thus, microbiome-targeted interventions such as probiotics represent a promising therapeutic strategy.

Bifidobacterium longum BBH016 is a probiotic strain originally isolated from a healthy human donor and classified as "Generally Recognized as Safe" (GRAS). Preclinical studies, including murine colitis models and Wistar rat models of stress-induced gut dysfunction, have demonstrated that oral administration of BBH016 ameliorates abdominal symptoms, reduces mucosal inflammation, restores microbial diversity, and improves functional pathways predicted by KEGG analyses. The strain has been formulated as a freeze-dried encapsulated product (1×10⁹ CFU/day) that is stable at refrigerated temperatures and suitable for clinical use.

This investigator-initiated, Ministry of Trade, Industry and Energy (MOTIE)-funded study aims to evaluate the efficacy and safety of B. longum BBH016 capsules in adults with lower GI symptoms, excluding constipation-predominant presentations. The trial is designed as a prospective, randomized, double-blind, placebo-controlled study conducted at Seoul National University Bundang Hospital. A total of 88 participants aged 19-80 years will be enrolled and randomized in a 1:1 ratio to receive either BBH016 capsules or placebo for 8 weeks (two capsules twice daily).

The primary endpoint is the overall improvement in GI symptoms, assessed at 8 weeks compared with baseline, between the BBH016 and placebo groups. Secondary endpoints include changes in individual symptom scores (abdominal pain, bloating, diarrhea, loose stool), global IBS Symptom Severity Score (IBS-SSS), quality of life (IBS-QoL), stool frequency and form (Bristol Stool Form Scale), and psychological status (Hospital Anxiety and Depression Scale, HADS). In addition, stool samples will be analyzed at baseline and week 8 to evaluate alterations in gut microbiome composition and diversity, and to explore correlations with symptom improvement.

Participants will undergo screening (V0), baseline/randomization (V1), an interim 4-week assessment (V2, telephone or in-person), and final evaluation at 8 weeks (V3). Safety will be assessed by monitoring adverse events, laboratory tests (hematology, chemistry, inflammatory markers), and vital signs. The trial is covered by clinical trial insurance, and all adverse events will be reported to the Institutional Review Board (IRB) according to regulatory requirements.

The study is expected to provide important clinical and mechanistic evidence for the use of BBH016 as a safe and effective probiotic therapy for functional lower GI symptoms. Compared with invasive interventions such as fecal microbiota transplantation (FMT), BBH016 capsules offer a standardized, stable, and convenient oral formulation that may be applicable even in secondary care settings. If efficacy and safety are confirmed, this trial could establish a novel, practical treatment option and a theoretical foundation for future use of BBH016 in patients with IBS and related disorders.

• Study Type: Interventional
• Enrollment (Estimated): 88
• Phase: Not Applicable

Contacts and Locations

Study Locations

• South Korea
  • 경기 - Gyeonggi-do
    • Seongnam-si, 경기 - Gyeonggi-do, South Korea, 13629
      • Seoul National University Bundang Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Male or female participants aged 19 to 80 years.
2. Subjects with lower gastrointestinal (GI) symptoms (diarrhea, loose stools, abdominal bloating, or excessive gas) in whom constipation is not the predominant symptom.

3. Subjects who have undergone colonoscopy within the past 5 years, or who will undergo colonoscopy after enrollment, with confirmation of no organic abnormalities in the colon.

   Records from another hospital within 5 years may be accepted. If colonoscopy included biopsy or polypectomy, subjects may be eligible if the investigator confirms no clinically significant abnormality.

4. Surgically sterile women or women of childbearing potential with a negative pregnancy test (urine hCG or serum β-hCG).

   Women of childbearing potential must agree to use appropriate contraception (e.g., oral contraceptives, intrauterine device [IUD], double-barrier method, or hormonal implant) throughout the study.

5. Subjects without major neurological or psychiatric disorders that impair decision-making capacity.

   Those with such conditions may still be eligible if deemed adequately controlled with medication or therapy.

6. Subjects who voluntarily provide written informed consent after receiving adequate explanation of the study.

Exclusion Criteria:

1. Subjects with constipation as the predominant lower GI symptom.
2. Pregnant or breastfeeding women.
3. Participation in another clinical trial and receipt of an investigational product within 3 months prior to screening.
4. Any condition judged by the investigator to pose a risk to the subject or interfere with study participation.
5. Severe congestive heart failure or severe angina.
6. Subjects with lactose intolerance or immunosuppression.

7. Use of medications that may affect the study product (e.g., GI medications, probiotics, antibiotics).

   Probiotics: may participate if discontinued ≥2 weeks before enrollment. Antibiotics or GI medications (potassium-competitive acid blocker, proton pump inhibitor, H2 receptor antagonist, pinaverium, trimebutine, etc.): may participate if discontinued ≥4 weeks before enrollment.

   If ongoing GI medication use is necessary, dose and regimen must remain unchanged during the study.

8. Uncontrolled hypertension (systolic BP >160 mmHg or diastolic BP >100 mmHg at screening), regardless of current therapy.

9. Uncontrolled endocrine or metabolic disease (e.g., diabetes, secondary hyperlipidemia) or hypothyroidism.

   Patients with hypothyroidism may be included if on stable replacement therapy for ≥4 weeks and TSH is within normal range at screening.

10. Impaired renal function (serum creatinine >2.0 mg/dL) or nephrotic syndrome at screening.
11. History of malignancy within the past 5 years (except those judged cured).
12. Major psychiatric instability or psychiatric disorders not adequately controlled by therapy.
13. Use of systemic corticosteroids within 1 month prior to screening.

14. History of abdominal surgery other than appendectomy, cholecystectomy, cesarean section, hysterectomy, or hernia repair.

    Other abdominal surgeries may be allowed if deemed appropriate by the investigator.

15. Any other condition judged by the investigator to make the subject unsuitable for participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Matching placebo capsule (2 caps BID for 8 weeks)	Dietary supplement: Placebo Capsule(s); placebo capsule (2 caps BID for 8 weeks)
Experimental: Experimental_BBH016 capsule; Bifidobacterium longum BBH016 capsule (2 caps BID for 8 weeks)	Dietary supplement: Bifidobacterium longum BBH016; BBH016 capsule (2 caps BID for 8 weeks)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
General symptom scale assessment	Participants will rate overall improvement in gastrointestinal symptoms using a patient-reported numeric scale ranging from 0 to 10 (0 = no improvement; 10 = complete symptom improvement). Higher scores indicate greater symptom improvement.	8weeks post treatment initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IBS Symptom Severity Score (IBS-SSS)	The IBS Symptom Severity Score is a validated questionnaire assessing IBS symptom severity (range: 0-500), with higher scores indicating more severe symptoms.	8weeks post treatment initiation
IBS Quality of Life (IBS-QoL)	The IBS Quality of Life questionnaire assesses health-related quality of life in patients with IBS (range: 0-100), with higher scores indicating better quality of life.	8weeks post treatment initiation
Bristol stool form scale	The Bristol Stool Form Scale classifies stool form into 7 categories (1-7), with higher scores indicating looser stool consistency.	8weeks post treatment initiation
Abdominal Pain Severity Score (5-point Likert scale)	Participants will rate abdominal pain severity using a 5-point Likert scale (1-5) 1 = no symptoms; 5 = very severe symptoms. Higher scores indicate worse symptoms.	8 weeks post treatment initiation
Abdominal Discomfort Severity Score (5-point Likert scale)	Participants will rate abdominal discomfort severity using a 5-point Likert scale (1-5) 1 = no symptoms; 5 = very severe symptoms.	8 weeks post treatment initiation
Bloating Severity Score (5-point Likert scale)	Participants will rate bloating severity using a 5-point Likert scale (1-5) 1 = no symptoms; 5 = very severe symptoms.	8 weeks post treatment initiation
Flatulence Severity Score (5-point Likert scale)	Participants will rate flatulence severity using a 5-point Likert scale (1-5)	8 weeks post treatment initiation
HADS anxiety and depression score	The Hospital Anxiety and Depression Scale is a 14-item questionnaire assessing anxiety and depression symptoms (range: 0-42 total score), with higher scores indicating greater psychological distress.	8weeks post treatment initiation
Fecal Microbiome Analysis	Stool samples will be collected at baseline and week 8. The fecal microbiome will be analyzed using 16S rRNA gene sequencing to evaluate changes in microbial diversity and taxonomic composition between treatment groups and over time.	8weeks post treatment initiation

Collaborators and Investigators

• Sponsor: Seoul National University Bundang Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2025
• Primary Completion (Actual): February 24, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: February 27, 2026
• First Submitted That Met QC Criteria: March 16, 2026
• First Posted (Actual): March 20, 2026

Study Record Updates

• Last Update Posted (Actual): March 20, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: probiotics; Bifidobacterium longum BBH016
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Colonic Diseases, Functional; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Irritable Bowel Syndrome; Diarrhea
• Other Study ID Numbers: B-2505-971-004; 20018499 (Other Grant/Funding Number: Technology Innovation Program (20018499), Ministry of Trade, Industry and Energy)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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