distinct focal inflammatory areas in the bladder mucosa observed in a minority of patients diagnosed with IC/BPS. This is the first comprehensive evaluation of the microbiome of HL patients using… Click to show full abstract
distinct focal inflammatory areas in the bladder mucosa observed in a minority of patients diagnosed with IC/BPS. This is the first comprehensive evaluation of the microbiome of HL patients using a casecontrol design in an IC/BPS patient population. METHODS: The bacterial microbiota of mid-stream urine specimens from HL IC/BPS and age/gender matched IC/BPS subjects with no Hunner Lesions (NHL) were examined using state of the art next generation full-length 16S gene sequencing. The differential abundances and diversity of species were characterized and compared (R package DESeq2 v1.24.0) for HL and NHL as well as gender-specific HL and NHL subjects. RESULTS: IC/BPS subjects (total 59; 29 HL and 30 NHL; 43 female and 16 male) were analyzed as species grouped by HL/NHL and female/male designations. There were 10 (p < 0.05) significant species that differentiated HL from NHL urine specimens (though not significant after multiple testing correction). These included Streptococcus, Propionibacterium, Campylobacter, Atopobium, Anaerococcus, Actinomyces, Prevotella, Actinotignum, Gardnerella, and Peptoniphilus species. However, the difference between male and female subjects accounted for the majority of the variance observed in the total IC/BPS population. Similar findings were observed in respect to abundance analyses. In the female data set, there are 7 species abundances that significantly differ (p<0.05) between HL and NHL though only a single Lactobacillus species (L. crispatus) differed significantly after multiple testing correction. In the male subset, there were 11 species that were significantly different and the top 4 species were still significant after correction. The differences observed between HL and NHL species abundance appears to be driven, in part, by the male HL subjects. Diversity metrics (Shannon Diversity and Effective Number; see Figure) shows that both female HL and NHL are dominated by 5 different species and male HL by 10, while male NHL are less diverse at 6. CONCLUSIONS: There is a differential abundance of species in HL vs NHL, with the difference more pronounced in the male subset and much less clear between the female IC/BPS groups. Species differences between HL and NHL subjects are overshadowed by the strong differential clustering of species based on gender.
               
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