RIO DE JANEIRO, BRAZIL (UroToday.com) - Presented by Meghan M. Pearce, PhD, M.P.H,**,a Michael J. Zilliox, PhD,**,b Amy B. Rosenfeld,**,b Krystal J. Thomas-White,a Holly E. Richter, Ph.D., M.D.,c Charles W. Nager, MD,d Anthony G. Visco, M.D.,e Ingrid Nygaard, M.D,,f Matthew D. Barber, M.D., M.H.S,g Joseph Schaffer, M.D.,h Pamela Moalli, M.D, PhD,i Vivian W. Sung, M.D. M.P.H.,j Ariana L. Smith, M.D.,k R. Rogers, MD,l Tracy Nolen, DrPH,m Dennis Wallace, Ph.D.,m Susan F. Meikle, M.D. M.S.P.H.,n Xiaowu Gai, Ph.D,b Alan J. Wolfe, PhD,a and Linda Brubaker, M.D., M.S.a for the Pelvic Floor Disorders Network at the International Continence Society (ICS) 2014 Annual Meeting - October 20 - 24, 2014 - Rio de Janeiro, Brazil
ABSTRACT:
Hypothesis/Aims of Study
Using the quantitative polymerase chain reaction, we recently detected bacterial DNA in pre-treatment catheterized urine samples of female participants with urinary urgency incontinence (UUI) in the NICHD Anticholinergic versus Botulinum Toxin Comparison (ABC) Trial. The presence of bacterial DNA was associated with decreased risk of post-treatment urinary tract infection (UTI).[1, 2] The objective of this study was to use DNA sequencing to characterize bacterial communities in the urine of women without clinical infection before UUI study treatment and to explore associations with patient demographics, symptoms and clinical outcomes, especially post-treatment development of UTI.
Study Design, Materials, and Methods
Bacterial DNA was extracted from catheterized urine samples and amplified with universal primers that target the V4 region of the 16S ribosomal RNA gene. Samples were sequenced at least twice independently with Illumina’s MiSeq technology to assure data quality and reproducibility. Sequence reads were classified to bacterial genus. Sequence status was compared to clinical variables.
Results
Bacterial DNA was successfully amplified and sequenced in about half (51.1%, n=93/182, SEQ POS) of the urines. Race, ethnicity, prior anticholinergic use, or treatment did not differ between SEQ POS and SEQ NEG cohorts. However, women in the SEQ POS cohort were younger (p=0.0007), heavier (p=0.0009), had more baseline UUI episodes (p < 0.0001), responded better to UUI treatment (p=0.0013), and were less likely to develop UTI after initiation of UUI treatment (p=0.0011).
In SEQ POS urines, 8 major groups (termed urotypes) were identified. Most were dominated by a single bacterial genus (> 50% total sequence reads). Nearly half of the SEQ POS urines (45%) were dominated by Lactobacillus, followed by Gardnerella (17%), Gardnerella and Prevotella (9%), Enterobacteriaceae (9%), Staphylococcus (3%), Aerococcus (2%), and Bifidobacterium (2%). The rest (13%) were diverse without a dominant family. Race and ethnicity were similar across urotypes, but age differed (p=0.0094); urotypes dominated by Enterobacteriaceae, Staphylococcus and Aerococcus were only in post-menopausal women.
Relative to SEQ POS women who did not develop a post-treatment UTI, those who did develop a UTI had, on average, fewer Lactobacillus (20.6 vs 47.3% of total sequences per sample) and less diversity, but more Aerococcus (9.6 vs 1.2%), Bifidobacterium (9.8 vs 0.6%), Enterobacteriaceae (20.0 vs 6.9%), and Staphylococcus (9.1 vs 2.5%).
Interpretation of Results
Over half of female ABC trial participants with UUI, without evidence of clinical infection, contained sequenceable bacterial DNA in pre-treatment urines. The urotypes were typically dominated by a single genus, most often Lactobacillus or Gardnerella. Pre-treatment urotypes may be associated with risk of post-treatment UTI.
Concluding Message
The female urinary microbiome is related to clinical treatment outcomes of interest in women with UUI.
References:
- Brubaker L. Nager CW, Richter HE, Visco A, Nygaard I, Barber M, Schaffer J, Meikle S, Wallace D, Shibata N, Wolfe AJ. Urinary Bacteria in Adult Women with Urgency Urinary Incontinence. Int Urogynecol J. 2014 Feb 11 Epub ahead of print. PMID: 24515544.
- Visco A, Brubaker L, Richter H, Nygaard I, Paraiso MF, Menefee S, Schaffer J, Lowder J, Khandwala S, Sirls L, Spino C, Nolen T, Wallace D, Meikle S. Anticholinergics Therapy vs OnabotulinumtoxinA for Urgency Urinary Incontinence. New Engl J Med. 2012 Nov; 8;367(19):1803-1813. PMID:23036134.
Disclosures
Funding: none Clinical Trial: Yes Registration Number: Clinicaltrials.gov #NCT01166438 RCT: Yes Subjects: HUMAN Ethics Committee: IRB , Loyola University Chicago Helsinki: Yes Informed Consent: Yes
aDepartments of Microbiology and Immunology, Stritch School of Medicine, Loyola University, Chicago, Illinois, USA
bDepartment of Molecular Pharmacology and Therapeutics, Stritch School of Medicine, Loyola University, Chicago, Illinois, USA
cDepartment of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, Alabama, USA
dDepartment of Reproductive Medicine, UC San Diego Health System, San Diego, California, USA
eDepartment of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina, USA
fDepartment of Obstetrics and Gynecology, University of Utah, Salt Lake City, Utah, USA
gDepartment of Obstetrics and Gynecology, Cleveland Clinic, Cleveland, Ohio, USA
hDepartment of Obstetrics and Gynecology, University of Texas Southwest, Dallas, Texas, USA
iDepartment of Obstetrics and Gynecology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
jDepartment of Obstetrics and Gynecology, Alpert Medical School of Brown University, Providence, Rhode Island, USA
kDepartment of Urology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
lDepartment of Obstetrics and Gynecology, University of New Mexico, Albuquerque, New Mexico, USA
mRTI International, Research Triangle Park, NC USA
nContraception and Reproductive Health Branch, Center for Population Research, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health
** Drs. Pearce, Zilliox and Rosenfeld contributed equally to this work.