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

Overview

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.

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.