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

Abstract

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 < 0.0156). 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.

Keywords:

• Microbiome
• Urinary tract infection
• Neuropathic bladder
• Probiotics
• Safety study

Acknowledgements

The content of this work are solely the responsibility of the authors and do not necessarily represent the official views of the National Center for Advancing Translational Sciences or the National Institutes of Health.

Disclaimer statements

Contributors None.

Conflicts of interest Drs Caldovic, Pohl, and Groah have submitted a patent for the intravesical use of Lactobacillus.

Additional information

Funding

This work was funded by Patient-Centered Outcomes Research Institute (PCORI) [Grant Number AD-1310-08215]. This work was supported by Eunice Kennedy Shriver National Institute of Child Health and Human Development [Grant Number K12 HD001399]; National Center for Advancing Translational Sciences [Grant Number UL1TR001876]; National Center for Advancing Translational Sciences [Grant Number KL2TR001877]; National Institutes of Health [Grant Number K12HL119994]; National Institutes of Health (US) [Grant Number RO1: KO113504].