Lower Abdominal Pain, Diarrhea, Irritable Bowel Syndrome
Conditions
Keywords
Bifidobacterium longum BBH016, probiotics
Brief summary
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.
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.
Interventions
DIETARY_SUPPLEMENTBifidobacterium longum BBH016
BBH016 capsule (2 caps BID for 8 weeks)
DIETARY_SUPPLEMENTPlacebo Capsule(s)
placebo capsule (2 caps BID for 8 weeks)
Sponsors
Seoul National University Bundang Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
Prospective, randomized, double-blind, placebo-controlled, single-center trial at SNUBH. Adults 19-80 with lower GI symptoms (abdominal pain, diarrhea/loose stools, bloating) without organic disease; constipation-predominant presentations excluded. After screening (eligibility, labs, colonoscopy confirmation per protocol), participants are randomized 1:1 to BBH016 (two capsules twice daily) or identical placebo for 8 weeks. Visits at baseline (V1), week 4 (V2; in-person or phone), and week 8 (V3); stool collected at V1 and V3; safety labs at V0/V1/V3. Primary endpoint: overall improvement in GI symptoms at week 8 vs baseline between groups. Secondary endpoints: symptom subscores, IBS-SSS, IBS-QoL, BSFS, HADS, and gut microbiome changes. Safety monitoring includes AEs, vitals, and laboratory parameters; trial insurance in place; blinding maintained for participants, investigators, and staff.
Eligibility
Sex/Gender
ALL
Age
19 Years to 80 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| General symptom scale assessment | 8weeks post treatment initiation | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| IBS Symptom Severity Score (IBS-SSS) | 8weeks post treatment initiation | The IBS Symptom Severity Score is a validated questionnaire assessing IBS symptom severity (range: 0-500), with higher scores indicating more severe symptoms. |
| IBS Quality of Life (IBS-QoL) | 8weeks post treatment initiation | 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. |
| Bristol stool form scale | 8weeks post treatment initiation | The Bristol Stool Form Scale classifies stool form into 7 categories (1-7), with higher scores indicating looser stool consistency. |
| Abdominal Pain Severity Score (5-point Likert scale) | 8 weeks post treatment initiation | 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. |
| Abdominal Discomfort Severity Score (5-point Likert scale) | 8 weeks post treatment initiation | Participants will rate abdominal discomfort severity using a 5-point Likert scale (1-5) 1 = no symptoms; 5 = very severe symptoms. |
| Bloating Severity Score (5-point Likert scale) | 8 weeks post treatment initiation | Participants will rate bloating severity using a 5-point Likert scale (1-5) 1 = no symptoms; 5 = very severe symptoms. |
| Flatulence Severity Score (5-point Likert scale) | 8 weeks post treatment initiation | Participants will rate flatulence severity using a 5-point Likert scale (1-5) |
| HADS anxiety and depression score | 8weeks post treatment initiation | 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. |
| Fecal Microbiome Analysis | 8weeks post treatment initiation | 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. |
Countries
South Korea
Outcome results
None listed