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      The Role of Gut, Vaginal, and Urinary Microbiome in Urinary Tract Infections: From Bench to Bedside

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          Abstract

          The current paradigm of urinary tract infection (UTI) pathogenesis takes into account the contamination of the periurethral space by specific uropathogens residing in the gut, which is followed by urethral colonization and pathogen ascension to the urinary bladder. Consequently, studying the relationship between gut microbiota and the subsequent development of bacteriuria and UTI represents an important field of research. However, the well-established diagnostic and therapeutic paradigm for urinary tract infections (UTIs) has come into question with the discovery of a multifaceted, symbiotic microbiome in the healthy urogenital tract. More specifically, emerging data suggest that vaginal dysbiosis may result in Escherichia coli colonization and prompt recurrent UTIs, while urinary microbiome perturbations may precede the development of UTIs and other pathologic conditions of the urinary system. The question is whether these findings can be exploited for risk reduction and treatment purposes. This review aimed to appraise the three aforementioned specific microbiomes regarding their potential influence on UTI development by focusing on the recent studies in the field and assessing the potential linkages between these different niches, as well as evaluating the state of translational research for novel therapeutic and preventative approaches.

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          Urinary tract infections: epidemiology, mechanisms of infection and treatment options.

          Urinary tract infections (UTIs) are a severe public health problem and are caused by a range of pathogens, but most commonly by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterococcus faecalis and Staphylococcus saprophyticus. High recurrence rates and increasing antimicrobial resistance among uropathogens threaten to greatly increase the economic burden of these infections. In this Review, we discuss how basic science studies are elucidating the molecular details of the crosstalk that occurs at the host-pathogen interface, as well as the consequences of these interactions for the pathophysiology of UTIs. We also describe current efforts to translate this knowledge into new clinical treatments for UTIs.
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            Current understanding of the human microbiome

            Our understanding of the link between the human microbiome and disease, including obesity, inflammatory bowel disease, arthritis and autism, is rapidly expanding. Improvements in the throughput and accuracy of DNA sequencing of the genomes of microbial communities associated with human samples, complemented by analysis of transcriptomes, proteomes, metabolomes and immunomes, and mechanistic experiments in model systems, have vastly improved our ability to understand the structure and function of the microbiome in both diseased and healthy states. However, many challenges remain. In this Review, we focus on studies in humans to describe these challenges, and propose strategies that leverage existing knowledge to move rapidly from correlation to causation, and ultimately to translation.
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              The gut microbiome in health and in disease

              Recent technological advancements and expanded efforts have led to a tremendous growth in the collective knowledge of the human microbiome. This review will highlight some of the important recent findings in this area of research.
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                Author and article information

                Journal
                Diagnostics (Basel)
                Diagnostics (Basel)
                diagnostics
                Diagnostics
                MDPI
                2075-4418
                22 December 2020
                January 2021
                : 11
                : 1
                : 7
                Affiliations
                [1 ]University Centre Varaždin, University North, 42 000 Varaždin, Croatia; tmestrovic@ 123456unin.hr
                [2 ]Clinical Microbiology and Parasitology Unit, Dr. Zora Profozić Polyclinic, 10 000 Zagreb, Croatia
                [3 ]Center for Translational and Clinical Research, University of Zagreb School of Medicine, 10 000 Zagreb, Croatia; mihaela.peric@ 123456mef.hr (M.P.); hana.paljetak@ 123456mef.hr (H.Č.P.)
                [4 ]Division of Electronics, Ruđer Bošković Institute, 10 000 Zagreb, Croatia; anja.baresic@ 123456irb.hr
                [5 ]Department of Medical Biochemistry and Haematology, University of Zagreb Faculty of Pharmacy and Biochemistry, 10 000 Zagreb, Croatia; donatella.verbanac@ 123456pharma.unizg.hr
                Author notes
                [* ]Correspondence: mario.matijasic@ 123456mef.hr
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0001-9209-4611
                https://orcid.org/0000-0003-1303-3031
                Article
                diagnostics-11-00007
                10.3390/diagnostics11010007
                7822161
                33375202
                50344509-846f-4428-862e-5d3af5abe202
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 30 November 2020
                : 19 December 2020
                Categories
                Review

                microbiome,microbiota,gut microbiome,vaginal microbiome,urobiome,urinary tract,urinary tract infection,uti,bacteriuria,dysbiosis

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