MP46-01 DEFICIENCY OF HOST MICROBIOME BY ANTIBIOTIC EXPOSURE COMPROMISES INNATE IMMUNE RESPONSES OF THE URINARY BLADDER AGAINST UROPATHOGENIC E. COLI

Abstract

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder I (MP46)1 Apr 2020MP46-01 DEFICIENCY OF HOST MICROBIOME BY ANTIBIOTIC EXPOSURE COMPROMISES INNATE IMMUNE RESPONSES OF THE URINARY BLADDER AGAINST UROPATHOGENIC E. COLI Yan Liu, Abbey Lepor, Hongying Huang, Herbert Lepor, Xue-Ru Wu, and Ellen Shapiro* Yan LiuYan Liu More articles by this author , Abbey LeporAbbey Lepor More articles by this author , Hongying HuangHongying Huang More articles by this author , Herbert LeporHerbert Lepor More articles by this author , Xue-Ru WuXue-Ru Wu More articles by this author , and Ellen Shapiro*Ellen Shapiro* More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000901.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Host microbiome is critical for maintaining immune homeostasis and priming systemic and local immune responses. Little is known about whether microbiome perturbation affects innate responses of the bladder against infections caused by uropathogenic E. coli (UPEC). A recent population-based study showed a link between antibiotic use, gut microbiome perturbation and recurrent urinary tract infection (UTI). This study was to explore the effects of antibiotic-induced host microbiome perturbation on experimental UTI. METHODS: Antibiotic (Abx) treatment (1 g/L each of ampicillin, neomycin, metronidazole, 0.5 g/L of vancomycin in drinking water) started for conventionally raised female mouse breeders (129/SvEv strain), continued during pregnancy until after weaning of the offspring which were treated for 2 more weeks. Treatment ceased 10 days before UPEC infection. Control mice received no Abx. Due to technical difficulties to quantify urine microbiome in mice, fecal microbiome was used as a surrogate by Q-PCR and 16S-rDNA MiSeq. Female mice (n=15) were transurethrally infected with UPEC strain UTI89 (107 cfu in 50 ul). Bladders were homogenized/plated to enumerate UPEC or immunostained with anti-E.coli, uroplakin Ia, p65 of NF-kB and Ly6G. Neutrophil infiltration was assessed by myeloperoxidase (MPO) assay. RESULTS: Abx treatment resulted in a 90% reduction of fecal microbiome and its diversity by 34% but it did not affect urinary tract anatomy, urothelial morphology or apical distribution of uroplakin Ia – the urothelial receptor for type 1-piliated UPEC. UPEC induced rapid activation of NF-kB in the umbrella cells in both the Abx-treated and control mice at 2 hours post-infection (hpi). However, bacterial colonization at 24 hpi was 5-fold higher in the Abx-treated mouse bladders than the controls. The number of intracellular bacterial communities at 12 and 24 hpi was 2.5-fold and 5-folder higher, respectively, in the Abx mice than in controls. In contrast, neutrophil infiltration and neutrophil MPO activity were significantly lower in the Abx mice. CONCLUSIONS: Our study provides the first experimental evidence demonstrating that the host microbiome plays a critical role in innate immune defenses against UTI and that its deficiency caused by early-age antibiotic exposure leads to compromised neutrophil infiltration and increased bacterial burden in the bladder. Further studies are needed to ascertain whether these effects are caused by gut and/or urinary microbiome. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e673-e673 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yan Liu More articles by this author Abbey Lepor More articles by this author Hongying Huang More articles by this author Herbert Lepor More articles by this author Xue-Ru Wu More articles by this author Ellen Shapiro* More articles by this author Expand All Advertisement PDF downloadLoading ...