Lucas Wauters1, Helena Slaets2, Kim De Paepe3, Matthias Ceulemans4, Suzan Wetzels5, Karlien Geboers6, Joran Toth4, Wannes Thys7, Raf Dybajlo7, Daan Walgraeve8, Erik Biessen5, Kristin Verbeke4, Jan Tack9, Tom Van de Wiele3, Niels Hellings2, Tim Vanuytsel10. 1. Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium; Translational Research in Gastrointestinal Disorders, KU Leuven, Leuven, Belgium; Translational Research in Gastrointestinal Disorders, KU Leuven, Leuven, Belgium. 2. Department of Immunology and Infection, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium. 3. Centre for Microbial Ecology and Technology, Ghent University, Ghent, Belgium. 4. Translational Research in Gastrointestinal Disorders, KU Leuven, Leuven, Belgium. 5. Experimental Vascular Pathology Group, Maastricht University Medical Centre, Maastricht, Netherlands. 6. Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium. 7. MY RESEARCH, Diepenbeek, Belgium. 8. Department of Gastroenterology, Jessa Ziekenhuis, Hasselt, Belgium. 9. Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium; Translational Research in Gastrointestinal Disorders, KU Leuven, Leuven, Belgium. 10. Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium; Translational Research in Gastrointestinal Disorders, KU Leuven, Leuven, Belgium. Electronic address: tim.vanuytsel@uzleuven.be.
Abstract
BACKGROUND: Current treatments for functional dyspepsia have limited efficacy or present safety issues. We aimed to assess spore-forming probiotics in functional dyspepsia as monotherapy or add-on therapy to long-term treatment with proton-pump inhibitors. METHODS: In this single-centre, randomised, double-blind, placebo-controlled pilot trial that took place at University Hospitals Leuven (Leuven, Belgium), adult patients (≥18 years) with functional dyspepsia (as defined by Rome IV criteria, on proton-pump inhibitors or off proton-pump inhibitors) were randomly assigned (1:1) via computer-generated blocked lists, stratified by proton-pump inhibitor status, to receive 8 weeks of treatment with probiotics (Bacillus coagulans MY01 and Bacillus subtilis MY02, 2·5 × 109 colony-forming units per capsule) or placebo consumed twice per day, followed by an open-label extension phase of 8 weeks. Individuals with a history of abdominal surgery, diabetes, coeliac or inflammatory bowel disease, active psychiatric conditions, and use of immunosuppressant drugs, antibiotics, or probiotics in the past 3 months were excluded. All patients and on-site study personnel were masked to treatment allocation in the first 8 weeks. Symptoms, immune activation, and faecal microbiota were assessed and recorded. The primary endpoint was a decrease of at least 0·7 in the postprandial distress syndrome (PDS) score of the Leuven Postprandial Distress Scale in patients with a baseline PDS score of 1 or greater (at least mild symptoms), assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT04030780. FINDINGS:Between June 3, 2019, and March 11, 2020, of 93 individuals assessed for eligibility, we included 68 patients with functional dyspepsia (51 [75%] women, mean age 40·1 years [SD 14·4], 34 [50%] on proton-pump inhibitors). We randomly assigned 32 participants to probiotics and 36 to placebo. The proportion of clinical responders was higher with probiotics (12 [48%] of 25) than placebo (six [20%] of 30; relative risk 1·95 [95% CI 1·07-4·11]; p=0·028). The number of patients with adverse events was similar with probiotics (five [16%] of 32) and placebo (12 [33%] of 36). Two serious adverse events occurring during the open-label phase (appendicitis and syncope in two separate patients) were assessed as unlikely to be related to the study product. INTERPRETATION: In this exploratory study, B coagulans MY01 and B subtilis MY02 were efficacious and safe in the treatment of functional dyspepsia. Participants had potentially beneficial immune and microbial changes, which could provide insights into possible underlying mechanisms as future predictors or treatment targets. FUNDING: MY HEALTH.
RCT Entities:
BACKGROUND: Current treatments for functional dyspepsia have limited efficacy or present safety issues. We aimed to assess spore-forming probiotics in functional dyspepsia as monotherapy or add-on therapy to long-term treatment with proton-pump inhibitors. METHODS: In this single-centre, randomised, double-blind, placebo-controlled pilot trial that took place at University Hospitals Leuven (Leuven, Belgium), adult patients (≥18 years) with functional dyspepsia (as defined by Rome IV criteria, on proton-pump inhibitors or off proton-pump inhibitors) were randomly assigned (1:1) via computer-generated blocked lists, stratified by proton-pump inhibitor status, to receive 8 weeks of treatment with probiotics (Bacillus coagulansMY01 and Bacillus subtilis MY02, 2·5 × 109 colony-forming units per capsule) or placebo consumed twice per day, followed by an open-label extension phase of 8 weeks. Individuals with a history of abdominal surgery, diabetes, coeliac or inflammatory bowel disease, active psychiatric conditions, and use of immunosuppressant drugs, antibiotics, or probiotics in the past 3 months were excluded. All patients and on-site study personnel were masked to treatment allocation in the first 8 weeks. Symptoms, immune activation, and faecal microbiota were assessed and recorded. The primary endpoint was a decrease of at least 0·7 in the postprandial distress syndrome (PDS) score of the Leuven Postprandial Distress Scale in patients with a baseline PDS score of 1 or greater (at least mild symptoms), assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT04030780. FINDINGS: Between June 3, 2019, and March 11, 2020, of 93 individuals assessed for eligibility, we included 68 patients with functional dyspepsia (51 [75%] women, mean age 40·1 years [SD 14·4], 34 [50%] on proton-pump inhibitors). We randomly assigned 32 participants to probiotics and 36 to placebo. The proportion of clinical responders was higher with probiotics (12 [48%] of 25) than placebo (six [20%] of 30; relative risk 1·95 [95% CI 1·07-4·11]; p=0·028). The number of patients with adverse events was similar with probiotics (five [16%] of 32) and placebo (12 [33%] of 36). Two serious adverse events occurring during the open-label phase (appendicitis and syncope in two separate patients) were assessed as unlikely to be related to the study product. INTERPRETATION: In this exploratory study, B coagulans MY01 and B subtilis MY02 were efficacious and safe in the treatment of functional dyspepsia. Participants had potentially beneficial immune and microbial changes, which could provide insights into possible underlying mechanisms as future predictors or treatment targets. FUNDING: MY HEALTH.
Authors: Christopher J Black; Peter A Paine; Anurag Agrawal; Imran Aziz; Maria P Eugenicos; Lesley A Houghton; Pali Hungin; Ross Overshott; Dipesh H Vasant; Sheryl Rudd; Richard C Winning; Maura Corsetti; Alexander C Ford Journal: Gut Date: 2022-07-07 Impact factor: 31.793