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

Top Spinal Cord Inj Rehabil. 2023 Summer;29(3):44-57. doi: 10.46292/sci23-00004. Epub 2023 Aug 16.

Abstract

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.

Keywords: 16S rRNA; Lactobacillus; dysbiosis; microbiota; neurogenic bladder; spinal cord injuries.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Humans
  • Lacticaseibacillus rhamnosus*
  • Microbiota*
  • Pilot Projects
  • RNA, Ribosomal, 16S
  • Spinal Cord Injuries* / complications
  • Urinary Bladder, Neurogenic* / therapy
  • Urinary Tract*

Substances

  • RNA, Ribosomal, 16S

Grants and funding

Financial Support This project was supported by PCORI award AD1310-08215.