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Intravesical Lactobacillus rhamnosus GG Alters Urobiome Composition and Diversity Among People With Neurogenic Lower Urinary Tract Dysfunction.

  • 2023
  • Topics in spinal cord injury rehabilitation 29(3)
    • Suzanne L Groah
    • Amanda K Rounds
    • Marcos Pérez-Losada

Study Design

Type
Clinical Trial
Sample size
n = 26
Population
26 participants (SCI/D = 23; multiple sclerosis = 2; spina bifida = 1) between 20 and 57 years of age
Methods
pilot substudy within an 18-month phase 1 clinical trial of self-instilled intravesical LGG for urinary symptoms as directed by the Self-Management Protocol using Probiotics (SMP-Pro); urine samples collected monthly and at trigger symptoms, pre- and post-LGG instillation; 16S rRNA sequencing
Blinding
Open-label
Duration
18-month

Background

Neurogenic bladder is associated with bacterial colonization and frequent urinary tract infections.

Objectives

To explore the effects of one to two doses of intravesical Lactobacillus rhamnosus GG (LGG) on the urobiomes of adults with spinal cord injury/disease (SCI/D) who manage their bladders with intermittent catheterization (IC).

Methods

This was a pilot substudy within an 18-month phase 1 clinical trial of self-instilled intravesical LGG for urinary symptoms as directed by the Self-Management Protocol using Probiotics (SMP-Pro). Urine samples were collected monthly when participants were asymptomatic. When SMP-Pro "trigger" symptoms (cloudier and/or more foul-smelling urine) occurred, urine samples were collected immediately pre-LGG instillation and 24 to 48 hours after LGG instillation. Urine was collected via a new catheter, immediately placed on ice/freezer, and processed within 12 hours. Genomic DNA was isolated, and the V4 region of the 16S rRNA bacterial gene was amplified and high throughput sequenced. Amplicon sequence variants were inferred and bacterial composition, community structure, and variation across clinical phenotypes were determined.

Results

126 urine samples were collected from 26 participants (SCI/D = 23; multiple sclerosis = 2; spina bifida = 1) between 20 and 57 years of age. The urobiomes were characterized by four dominant phyla (>1%): Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria, which were comprised of six dominant genera (>3%): Escherichia/Shigella (29.1%), Klebsiella (22.4%), Proteus (15.2%), Aerococcus (6.3%), Streptococcus (6.0%), and Pluralibacter (3.0%). Post-LGG samples were associated with a decline in Escherichia/Shigella predominance (p < .001) and altered bacterial diversity (p < .05).

Conclusion

Among people with SCI/D who use IC, intravesical LGG alters the bacterial composition and diversity of the urine ecosystem, potentially disrupting the uropathogenic urobiome.

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