A single intravesical instillation of Lactobacillus rhamnosus GG is safe in children and adults with neuropathic bladder: A phase Ia clinical trial

Context/objective: Manipulation of the microbiome is an emerging approach to promote health. We conducted a Phase Ia safety study of a single bladder instillation of probiotics in asymptomatic patients with neuropathic bladder to determine the tolerability and safety of a single Lactobacillus instillation. Design: Phase Ia safety study. Setting: Outpatient rehabilitation clinic at a rehabilitation hospital (adults) and urology clinic at a free-standing children’s hospital (children). Participants: Ten patients with neuropathic bladder were included: five children with spina bifida and five adults with spinal cord injury. Interventions: A single Lactobacillus rhamnosus GG (Culturelle, 20 billion live organisms) instillation. Outcome measures: After the instillation, participants self-monitored symptoms using the Urinary Symptoms Questionnaire for People with Neuropathic Bladder using Intermittent Catheterization daily for one week. Repeat urinalysis, urine culture, and 16S bacterial rRNA-based microbiome analyses were performed 7–10 days after instillation. Results: Probiotic instillation was well-tolerated. One child had upper respiratory tract symptoms during the trial, and two had transient cloudy urine. No adults reported any symptoms following instillation. Lactobacillus did not grow on culture post-instillation. There were differences in beta diversity of the urine microbiome in children vs. adults with neuropathic bladder (P Lactobacillus was present in the pre-instillation urinary microbiomes all of the adults and 4 out of 5 of the pediatric subjects, and identified in 4 out of 5 of both the adult and pediatric subjects’ post-instillation urinary microbiomes. Conclusion: Intravesical instillation of Culturelle probiotic may be safe and well-tolerated in patients with neuropathic bladder.