Dataset Information

Integrated next-generation sequencing of 16S rDNA and metaproteomics differentiate the healthy urine microbiome from asymptomatic bacteriuria in neuropathic bladder associated with spinal cord injury.

ABSTRACT:

Background

Clinical dogma is that healthy urine is sterile and the presence of bacteria with an inflammatory response is indicative of urinary tract infection (UTI). Asymptomatic bacteriuria (ABU) represents the state in which bacteria are present but the inflammatory response is negligible. Differentiating ABU from UTI is diagnostically challenging, but critical because overtreatment of ABU can perpetuate antimicrobial resistance while undertreatment of UTI can result in increased morbidity and mortality. In this study, we describe key characteristics of the healthy and ABU urine microbiomes utilizing 16S rRNA gene (16S rDNA) sequencing and metaproteomics, with the future goal of utilizing this information to personalize the treatment of UTI based on key individual characteristics.

Methods

A cross-sectional study of 26 healthy controls and 27 healthy subjects at risk for ABU due to spinal cord injury-related neuropathic bladder (NB) was conducted. Of the 27 subjects with NB, 8 voided normally, 8 utilized intermittent catheterization, and 11 utilized indwelling Foley urethral catheterization for bladder drainage. Urine was obtained by clean catch in voiders, or directly from the catheter in subjects utilizing catheters. Urinalysis, urine culture and 16S rDNA sequencing were performed on all samples, with metaproteomic analysis performed on a subsample.

Results

A total of 589454 quality-filtered 16S rDNA sequence reads were processed through a NextGen 16S rDNA analysis pipeline. Urine microbiomes differ by normal bladder function vs. NB, gender, type of bladder catheter utilized, and duration of NB. The top ten bacterial taxa showing the most relative abundance and change among samples were Lactobacillales, Enterobacteriales, Actinomycetales, Bacillales, Clostridiales, Bacteroidales, Burkholderiales, Pseudomonadales, Bifidobacteriales and Coriobacteriales. Metaproteomics confirmed the 16S rDNA results, and functional human protein-pathogen interactions were noted in subjects where host defenses were initiated.

Conclusions

Counter to clinical belief, healthy urine is not sterile. The healthy urine microbiome is characterized by a preponderance of Lactobacillales in women and Corynebacterium in men. The presence and duration of NB and method of urinary catheterization alter the healthy urine microbiome. An integrated approach of 16S rDNA sequencing with metaproteomics improves our understanding of healthy urine and facilitates a more personalized approach to prevention and treatment of infection.

SUBMITTER: Fouts DE

PROVIDER: S-EPMC3511201 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Publications

Integrated next-generation sequencing of 16S rDNA and metaproteomics differentiate the healthy urine microbiome from asymptomatic bacteriuria in neuropathic bladder associated with spinal cord injury.

Fouts Derrick E DE Pieper Rembert R Szpakowski Sebastian S Pohl Hans H Knoblach Susan S Suh Moo-Jin MJ Huang Shih-Ting ST Ljungberg Inger I Sprague Bruce M BM Lucas Sarah K SK Torralba Manolito M Nelson Karen E KE Groah Suzanne L SL

Journal of translational medicine 20120828

<h4>Background</h4>Clinical dogma is that healthy urine is sterile and the presence of bacteria with an inflammatory response is indicative of urinary tract infection (UTI). Asymptomatic bacteriuria (ABU) represents the state in which bacteria are present but the inflammatory response is negligible. Differentiating ABU from UTI is diagnostically challenging, but critical because overtreatment of ABU can perpetuate antimicrobial resistance while undertreatment of UTI can result in increased morbi ...[more]

PMID: 22929533

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Project description:Asymptomatic bacteriuria is a bacterial infection of the urine without any of the typical symptoms that are associated with a urinary infection, and occurs in 2% to 15% of pregnancies. If left untreated, up to 30% of mothers will develop acute pyelonephritis. Asymptomatic bacteriuria has been associated with low birthweight and preterm birth. This is an update of a review last published in 2015. To assess the effect of antibiotic treatment for asymptomatic bacteriuria on the development of pyelonephritis and the risk of low birthweight and preterm birth. For this update, we searched the Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) on 4 November 2018, and reference lists of retrieved studies. Randomised controlled trials (RCT) comparing antibiotic treatment with placebo or no treatment in pregnant women with asymptomatic bacteriuria found on antenatal screening. Trials using a cluster-RCT design and quasi-RCTs were eligible for inclusion, as were trials published in abstract or letter form, but cross-over studies were not. Two review authors independently assessed trials for inclusion and risk of bias, extracted data, and checked for accuracy. We assessed the quality of the evidence using the GRADE approach. We included 15 studies, involving over 2000 women. Antibiotic treatment compared with placebo or no treatment may reduce the incidence of pyelonephritis (average risk ratio (RR) 0.24, 95% confidence interval (CI) 0.13 to 0.41; 12 studies, 2017 women; low-certainty evidence). Antibiotic treatment may be associated with a reduction in the incidence of preterm birth (RR 0.34, 95% CI 0.13 to 0.88; 3 studies, 327 women; low-certainty evidence), and low birthweight babies (average RR 0.64, 95% CI 0.45 to 0.93; 6 studies, 1437 babies; low-certainty evidence). There may be a reduction in persistent bacteriuria at the time of delivery (average RR 0.30, 95% CI 0.18 to 0.53; 4 studies; 596 women), but the results were inconclusive for serious adverse neonatal outcomes (average RR 0.64, 95% CI 0.23 to 1.79, 3 studies; 549 babies). There were very limited data on which to estimate the effect of antibiotics on other infant outcomes, and maternal adverse effects were rarely described. Overall, we judged only one trial at low risk of bias across all domains; the other 14 studies were assessed as high or unclear risk of bias. Many studies lacked an adequate description of methods, and we could only judge the risk of bias as unclear, but in most studies, we assessed at least one domain at high risk of bias. We assessed the quality of the evidence for the three primary outcomes with GRADE software, and found low-certainty evidence for pyelonephritis, preterm birth, and birthweight less than 2500 g. Antibiotic treatment may be effective in reducing the risk of pyelonephritis in pregnancy, but our confidence in the effect estimate is limited given the low certainty of the evidence. There may be a reduction in preterm birth and low birthweight with antibiotic treatment, consistent with theories about the role of infection in adverse pregnancy outcomes, but again, the confidence in the effect is limited given the low certainty of the evidence. Research implications identified in this review include the need for an up-to-date cost-effectiveness evaluation of diagnostic algorithms, and more evidence to learn whether there is a low-risk group of women who are unlikely to benefit from treatment of asymptomatic bacteriuria.

Dataset Information

Integrated next-generation sequencing of 16S rDNA and metaproteomics differentiate the healthy urine microbiome from asymptomatic bacteriuria in neuropathic bladder associated with spinal cord injury.

Background

Methods

Results

Conclusions

Publications

Integrated next-generation sequencing of 16S rDNA and metaproteomics differentiate the healthy urine microbiome from asymptomatic bacteriuria in neuropathic bladder associated with spinal cord injury.

Similar Datasets

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