Probiotics and Biomarkers in Irritable Bowel Syndrome

Overview

The goal of this double-blind parallel-arm randomized controlled trial is to learn if a probiotic supplement (containing a new strain derived from L. reuteri) alters outcomes related to symptom severity and transit time in adults with irritable bowel syndrome (IBS). The main question it aims to answer is: Does the probiotic alter IBS symptom severity? Researchers will compare the probiotic to a placebo (a lookalike substance that contains no probiotic) to see if the probiotic works to alter outcomes. Participants will: Be randomized to either take the probiotic supplement or placebo supplement daily for 12 weeks. Visit the lab for 4 study visits (visit 1: screening and informed consent; visit 2: randomization, data collection, beginning the intervention; visit 3: end of intervention and data collection; visit 4: 3 month post intervention follow up and data collection). Provide biological samples (blood, stool, saliva, urine) Complete questionnaires

The BIO-IBS study is a double-blind, randomized, placebo-controlled clinical trial investigating whether a combination probiotic improves symptoms in adults with irritable bowel syndrome (IBS). The trial also explores biological mechanisms and predictors of treatment response. Background \& Rationale IBS is a common disorder of gut-brain interaction (\~4% prevalence in Sweden). Current treatments include dietary, pharmacological, and psychological approaches. Increasing evidence suggests the gut microbiome plays a key role, prompting interest in probiotics. Aims 1\. Evaluate effect of probiotic combination on IBS symptoms. 2, Identify predictors of response. 3. Investigate IBS pathophysiology and biomarkers. Study Design Type: Double-blind, randomized, placebo-controlled, parallel-group Participants: 252 adults with IBS Randomization: 1:1 (probiotic vs placebo) Treatment duration: 12 weeks Follow-up: 3 months post-treatment Timeline: Recruitment starting April 2026 lasting \~3 years Participants Inclusion Criteria Adult (≥18 years), IBS (Rome IV criteria) IBS-SSS \> 75 BMI 18.5-35 Able to consent and complete Swedish questionnaires Key Exclusion Criteria Significant gastrointestinal or systemic disease Recent antibiotics (within 3 months) or probiotics (within 2 weeks) Opioid use Pregnancy/breastfeeding Significant lab abnormalities (e.g., high fecal calprotectin) Major lifestyle/treatment changes Intervention Active treatment: Tablet containing both L. reuteri strains Placebo: Identical without bacteria Dose: 1 tablet twice daily Duration: 12 weeks Compliance ≥80% required for per-protocol analysis. Outcomes Primary Outcome Change in IBS symptom severity (IBS-SSS) from baseline to 12 weeks (intervention vs placebo) Secondary Outcomes Proportion achieving ≥50 or ≥100 point IBS-SSS reduction Gastrointestinal symptoms (GSRS-IBS) Pain reduction Quality of life (IBSQOL) Work productivity (WPAI:IBS) Transit time (gut motility) Adverse events Sustainability of effects (3-month follow-up) Exploratory Outcomes Stool consistency/frequency Biomarkers (microbiome, immune, metabolomics, etc.) Psychological and lifestyle factors Dietary influences Mechanistic insights into IBS Study Procedures Visits Screening (2-8 weeks before randomization Consent, questionnaires, biological samples, diaries Randomization (Day 0) Baseline assessments and start of treatment During intervention Regular symptom tracking Phone follow-up at week 6 End of treatment (12 weeks) Repeat assessments and samples Follow-up (3 months later) Long-term outcomes Optional (Facultative) Assessments Rectal sensitivity (barostat) Sigmoidoscopy ± confocal endomicroscopy MRI (motility and colonic volume) Measurements Questionnaires: IBS-SSS, GSRS-IBS, HADS, PHQ-15, IBSQOL, stress, work productivity Biological samples: blood, stool, urine, saliva Gut function: transit time (radiopaque markers and sweetcorn method) Diet: food frequency and recall diaries Statistical Considerations Sample size: 252 participants (powered to detect clinically meaningful IBS-SSS difference) Populations: Intention-to-treat (all randomized) Per-protocol (≥80% compliance, no major deviations) Analysis plan: Defined in a Statistical Analysis Plan No interim analysis Safety Probiotics considered safe with minimal risk (mainly transient flatulence). Adverse events will be recorded and classified by severity and causality. IBS symptom fluctuations are not counted as adverse events unless worsened. Ethics \& Data Handling Conducted according to Declaration of Helsinki and ICH-GCP. Participants give informed consent and can withdraw anytime. Data are pseudonymized and securely stored (REDCap) Risk-Benefit Assessment Low risk due to established safety of L. reuteri strains Moderate participant burden (questionnaires, sample collection) Optional procedures may cause discomfort but are controlled and voluntary Potential benefit: improved IBS symptoms and better understanding of disease mechanisms Key Strengths Large sample size Rigorous randomized controlled design Comprehensive symptom, biological, and mechanistic assessment Long follow-up Conclusion This study aims to determine whether a novel probiotic combination improves IBS symptoms and to identify biological and clinical predictors of response, contributing to more personalized treatment strategies in IBS.