Abstract
Male lower urinary tract symptoms (LUTS) comprise a common syndrome of aging that negatively impacts quality of life. The etiology of LUTS is multifactorial, involving benign prostatic hyperplasia, smooth muscle and neurologic dysfunction, inflammation, sexually transmitted infections, fibrosis, and potentially dysbiosis, but this aspect remains poorly explored. We investigated whether the presence of infectious agents in urine might be associated with LUTS by combining next-generation DNA sequencing for virus discovery, microbiome analysis for characterization of bacterial communities, and mass spectrometry-based metabolomics. In urine from 29 LUTS cases and 9 controls from Wisconsin, we found a statistically significant association between a diagnosis of LUTS and the presence of JC virus (JCV), a common neurotropic human polyomavirus (Polyomaviridae, Betapolyomavirus) linked to severe neurologic disease in rare cases. This association (based on metagenomics) was not borne out when specific polymerase chain reaction (PCR) testing was applied to this set of samples, likely due to the greater sensitivity of PCR. Interestingly, urine metabolomics analysis identified dysregulation of metabolites associated with key LUTS processes. Microbiome analysis found no evidence of microbial community dysbiosis in LUTS cases, but JCV-positive samples contained more Anaerococcus species, which are involved in polymicrobial infections of the urinary tract. Neither age nor body mass index were significantly associated with the presence of urinary JCV—in the initial group or in an additional, regionally distinct group. These data provide preliminary support the hypothesis that viruses such as JCV may play a role in the development or progression of LUTS, together with other infectious agents and host metabolic responses.
Highlights
Male lower urinary tract symptoms (LUTS) include frequency, urgency, and pain with urination [1]
polymerase chain reaction (PCR) identified 15 of the 29 LUTS samples to be positive for JC virus (JCV) (51.7%) and 3 of the 9 controls to be positive for JCV (33.3%)
Based on PCR data, the association between LUTS and JCV became not statistically significant due to the classification by PCR of three control samples that had previously tested negative by metagenomics
Summary
Male lower urinary tract symptoms (LUTS) include frequency, urgency, and pain with urination [1]. The human gastrointestinal microbiome responds to environmental factors such as xenobiotics, diet, and lifestyle, potentially leading to dysbiosis and increased incidence of metabolic syndrome and irritable bowel disease, among other conditions [11]. Efforts to rebalance the microbiome are gaining momentum, such as in the case of persistent bowel infection by Clostridium difficile, for which fecal microbiota transplantation is being considered for approval as an investigative new drug [17]. Such approaches could apply to diseases linked to dysbiosis of the urinary tract microbiome as well
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