Bacillus Probiotic Spores in Supporting the Treatment of Chronic Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) can affect individuals of all ages and is commonly associated with persistent diarrhea, abdominal pain, bloody stool, and, in some cases, extraintestinal manifestations such as arthritis, skin lesions, ocular involvement, and hepatobiliary disorders. If not well controlled, IBD may also increase the risk of colorectal cancer. The global incidence of IBD has been rising rapidly, including in Vietnam. Current therapies, including 5-aminosalicylic acid (5-ASA), corticosteroids, immunomodulators, biologic agents, and antibiotics when indicated. However, long-term disease management remains challenging.

Therapeutic strategies aimed at achieving sustained improvement in clinical symptoms and effective mucosal healing are increasingly recognized as important in IBD management. The gut microbiota plays a central role in intestinal inflammation, mucosal immune regulation, and epithelial barrier function. Therefore, probiotic intervention represents a potential supportive approach for patients with IBD. This approach may help improve clinical symptoms and support gut microbiota balance, while also potentially reducing barriers related to treatment costs and adverse effects associated with long-term or biological therapies. Among probiotic candidates, Bacillus species offer several advantages, including high survival under acidic and bile conditions, good room-temperature stability, suitability for oral formulation, and potential roles in mucosal immune modulation, digestive enzyme production, and inhibition of harmful bacteria.

The objective of this study is to evaluate the supportive therapeutic efficacy of multi-strain Bacillus spore probiotics in improving clinical symptoms in patients with IBD when used in combination with standard treatment, compared with standard treatment plus placebo, after 7, 14, and 30 days of using LiveSpo® COLON or the combined LiveSpo® DIA30 and LiveSpo® COLON regimen.

This will be a randomized, blinded, controlled clinical trial conducted over 12 months. Eligible patients aged 18-65 years with a confirmed diagnosis of inflammatory bowel disease, including ulcerative colitis or Crohn's disease, will be enrolled after providing written informed consent and meeting all eligibility criteria. A total of 150 participants will be randomly assigned to three groups (n = 50 per group): the Placebo group will receive oral RO water, the Colon group will receive LiveSpo® COLON, and the DIA30-COLON group will receive a combined regimen of LiveSpo® DIA30 and LiveSpo® COLON, with all groups continuing the hospital's standard IBD treatment regimen throughout the study period.

• Clinical assessments will be performed at baseline and on days 7, 14, and 30, while sub-clinical assessments, including blood parameters and cytokine levels in blood and stool samples, will be performed at baseline and on days 14 and 30. The main comparison will be based on changes from baseline to day 30. Exploratory analyses will assess changes in gut microbiome composition and endoscopic findings from baseline to day 30.
• The presence of Bacillus subtilis, Bacillus clausii, and Bacillus coagulans in stool samples will be assessed by real-time PCR at follow-up visits on days 7, 14, and 30 compared with day 0 to support assessment of product use compliance.
• Statistical analysis will be conducted using the chi-square test or Fisher's exact test for binary variables, and the t-test, Mann-Whitney test, or Wilcoxon test for continuous variables, depending on data distribution.

Inclusion criteria

• Age 18 to 65 years.
• Confirmed diagnosis of inflammatory bowel disease, including ulcerative colitis and Crohn's disease, according to the routine diagnostic procedures of Hanoi Medical University Hospital.
• Receiving examination and treatment at Hanoi Medical University Hospital (including both inpatients and outpatients), with a minimum treatment or follow-up duration of 14 days
• Willing and able to provide written informed consent.

Exclusion criteria

• Refusal to participate in the study.
• Withdrawal from the study before completing 14 days of treatment.
• Inability to comply with study procedures or inability to ensure adherence to the investigational product, as assessed by the investigator.
• Moderate to severe hepatic or renal dysfunction, or other moderate to severe chronic cardiovascular, pulmonary, hepatic, or renal diseases that may affect general health status or require specialist treatment.
• Presence of immune-related diseases.
• Current use, or use within 4 weeks prior to screening, of biologic immunosuppressive therapies (for example, anti-TNF-α agents or vedolizumab).