Whole-Person Approach to Urinary Tract Infection

Version	Summary	Created by	Modification	Content Size	Created at	Operation
1		Luciano Garofalo	+ 1853 word(s)	1853	2022-02-16 04:40:25	\|
2	format correction	Peter Tang	Meta information modification	1853	2022-02-17 02:24:56	\| \|
3	format correction	Peter Tang	Meta information modification	1853	2022-02-18 07:43:01	\|

This entry is adapted from the peer-reviewed paper 10.3390/antibiotics11020218

Urobiome dysbiosis, defined as an imbalance in the microbial composition in the microenvironments along the urinary tract, is found in women with uncomplicated urinary tract infection (UTI). Historically, antibiotics have been used to address UTI. An alternative approach to uncomplicated UTI is warranted as the current paradigm fails to take urobiome dysbiosis into account and contributes to the communal problem of resistance. A whole-person, multi-modal approach that addresses vaginal and urinary tract dysbiosis may be more effective in reducing recurrent UTI.

UTI cystitis dysbiosis microbiome microbiota urinary tract urinary tract infection urobiome vaginal microbiome alternative medicine

1. Introduction

Each year approximately 97 million outpatient visits are associated with antibiotic prescriptions, more of which are given for urinary tract infection (UTI) than any other diagnosis ^[1]^[2]. Urine culture and sensitivity testing are not recommended as the standard of care in the clinical diagnosis of UTI ^[3], and the management protocol is often irrespective of any clearly identifiable pathogen. Research has shown that antibiotic use is associated with an increased risk of recurrent UTI ^[4]. Moreover, antibiotic use within the past six months is a contributing risk factor for harboring resistant uropathogen isolates ^[5] and can facilitate cross-resistance when prescribed alongside non-antibiotics ^[6].

Trimethoprim–sulfamethoxazole (TMP–SMX) was recommended as first-line therapy in the treatment of acute uncomplicated bacterial cystitis by the Infectious Diseases Society of America guideline released in 2011 ^[7]. However, as TMP–SMX resistance has since escalated to a pooled worldwide average of 23.6% ^[8], providers may resort more to fluoroquinolones, causing an increase in the incidence of fluoroquinolone resistance among uropathogens, including ciprofloxacin-resistant Escherichia coli ^[9]. Fluoroquinolone resistance begets increasingly more dangerous infections such as hospital-acquired pneumonia and complicated UTI ^[10]. Exposure to fluoroquinolones has been associated with a more than 6-fold increased risk of acquiring C. difficile colitis ^[11]. Comparatively, patients who received TMP–SMX had a 2-fold higher risk of C. difficile colitis ^[11]. As the rates of incidence, recurrence, and therapeutic resistance of UTI rise, UTI treatment recommendations continue to evolve as part of the wider antibiotic stewardship effort.

Investigations into the efficacy of alternative therapies such as botanicals and probiotics have mostly been reduction-based, focusing on the impact of the substitute intervention on a singular physiological system in isolation. Many botanicals possess active constituents with antimicrobial properties or anti-adhesive effects that can aid in the treatment of UTI; however, more attention should be given to the complex mechanisms of action of complementary therapies as an integrative approach to Whole-Person Health (WPH).

1.1. Prevalence

UTI accounts for upwards of 10.5 million visits to physician offices and emergency departments per year and represents a significant portion of ambulatory healthcare costs ^[12]. UTI disproportionately affects women, with half of all women self-reporting at least one UTI by age 32 and 20–30% of women experiencing a second UTI within six months of initial infection ^[13]. These estimates do not include asymptomatic bacteriuria (ABU), occurring in 1% of schoolgirls, ≥2% of pregnant women, and about 20% of elderly individuals of both sexes ^[14]. Asymptomatic bacteriuria (ASB) is defined as the presence of ≥105 colony-forming units per mL of one or more bacterial species, irrespective of pyuria, in a urine specimen from a patient without signs or symptoms of UTI ^[15].

1.2. Pathophysiology

Infection typically begins when coliform bacteria contaminate the periurethral area and colonize the urethra through the expression of virulence and adhesion factors. From there, infection ascends to the bladder where bacterial multiplication is accomplished through the release of toxins and proteases that feed off host nutrients and instigate an inflammatory response ^[16]. By evading host immune surveillance, uropathogens can subsequently ascend to the kidneys, again attaching via adhesins or pili to colonize the renal epithelium and then produce tissue-damaging toxins ^[17].

1.3. Diagnostic Criteria

UTIs are categorized as either uncomplicated (simple) or complicated. Simple UTI, or simple cystitis, occurs primarily in otherwise healthy females of childbearing age. The prominent risk factors are prior UTI, new sexual partners (within the last year), vaginal infection, prolonged withholding of urine, and use of diaphragms or spermicides ^[18]. Complicated UTI is characterized by factors that disturb normal structure and function of the urinary tract, including indwelling catheters, anatomic variations or history of surgery in the urinary tract, renal insufficiency, neurogenic bladder, diabetes, pregnancy, and immunocompromised state (drug-induced, inherited, etc.). UTI in males is much less common and generally categorized as complicated ^[19].

1.4. Cystitis as a Spectrum of Etiologies

Lower urinary tract symptoms can present similarly for a variety of non-infectious urological disorders as well as UTI. Chronic bladder inflammation is subject to central sensitization and can have a variety of host- or environmentally mediated triggers ^[20]. For this reason, it can be difficult to distinguish bacterial infection from interstitial cystitis or other non-infectious etiologies in the primary care setting, especially for UTI that is considered recurrent or chronic. As a result, many patients with cystitis of non-infectious etiology receive unnecessary antibiotic prescriptions.

Bacteriuria in the absence of symptoms does not justify antibiotic prescription unless in a pregnant female ^[21]. Uropathogenic bacteria are found with increasing frequency in the urine as patients age due to compounding factors such as menopause, immunosenescence, and recurrent colonization by drug-resistant bacteria. These changes influence the urobiome and the etiology of cystitis, thus indicating different treatment approaches for older versus younger females ^[22]. ABU is common in the elderly and treating it with antibiotics is no longer recommended due to both a lack of mortality benefit and harm of antibiotic overuse ^[23].

Innate immunity, barrier defenses, and the urobiome may play more of a role than specific immunity in protecting the urinary tract from infection ^[24]. The urinary tract, and especially the bladder, has several physical, chemotactic, and immune-mediated barriers to infection. The urogenital epithelium is turned over at a high rate relative to other tissue due in part to the regular passing of acidic urine as well as the local immune system’s normal function. At a normal pH of 5.5 or less, urine helps discourage bacterial growth, and mucosal tissue in the urinary tract produces organic acids to combat pathogens. Unlike the body’s typical Th1-dominant response to bacterial invasion, the uroepithelium produces a Th2-dominant response, allowing for quicker overturn of compromised uroepithelium but generating progressively weaker bactericide and bacteriostasis ^[25].

Thus, the syndrome of cystitis, whether or not it is accompanied by a bacterial infection, can have one or several compounding etiologies (e.g., infection, dysbiosis, uroepithelial dysfunction, or central sensitization). These can be difficult to assess accurately in the clinical setting, especially for chronic and recurrent cases. Antibiotics can address pathogen overgrowth and resulting inflammation; however, they may also exacerbate dysbiosis, drive resistance, or contribute to the imbalance of other systems.

1.5. The Urobiome

The urinary tract has a microbiome whose taxa is similar to that of the gut, with Lactobacillus being the most commonly occurring species ^[26]^[27]^[28]. Alterations in the urinary microbiota have been linked to non-infectious urologic diseases, such as neurogenic bladder dysfunction, interstitial cystitis, and urgency urinary incontinence ^[29]. Urine from patients with interstitial cystitis exhibits lower bacterial diversity and a higher abundance of Lactobacillus when compared to healthy controls ^[30]. These findings suggest that some cases of “suspected UTI” could be symptomatic expressions of microbial dysbiosis, which might only be exacerbated by antibiotics. Additionally, the use of low-dose, prophylactic antibiotics to prevent recurrent infection could further contribute to pathogenic resistance evolution by creating bacterial persister cells. Persister cells are genetically similar to previous generations but exhibit a greater fitness and virulence, which serves to optimize their permanent colonization in the indigenous microbial environment ^[31].

Advancements in metagenomics have allowed us to explore the gut microbiome as a potential reservoir for resistant pathogens. The high alpha diversity of microbiota within this ecosystem easily facilitates the horizontal transfer of antimicrobial resistance genes to susceptible pathogens. The concept of this “resistome” may offer more knowledge beyond the epidemiologic considerations of clinical isolates alone ^[32]. The intestinal microbiota composition varies between different niche environments along the length of the digestive tract, influencing metabolism, intestinal epithelial cell proliferation and permeability, and modulating the immune response, either directly or through crosstalk. As such, dysbiosis of the gut microbiome has been linked to a multitude of diseases beyond the intestinal environment, including many in the urinary tract. Moreover, microbial metabolites in the gut and other organs distal to the kidneys, bladder, and urethra are likely to influence the urinary microbiome and its homeostasis ^[33].

Metabolomic assay analysis suggests that species population may not be as important as the resultant metabolic pathways created ^[34]. Individual populations can differ in composition but perform the same functions to preserve environmental homeostasis. Recurrent UTI may be associated with an inability to reconstitute the normal microbiota, either as a result of long-term antibiotic use or other underlying host factors ^[35]. Ideally, microbial diversity allows for sustained essential metabolic activity within the microenvironment. A microbiome consisting of multiple species of bacteria with the ability to perform the same functions serves as an insurance policy against bacterial death due to pharmaceutical and environmental disturbances.

2. Whole-Person Approach to UTI

While up to 50% of uncomplicated cystitis cases spontaneously resolve within one week ^[36], medical attention and intervention are still important. In addition to the risk of worsening infection such as pyelonephritis, symptoms may take longer to clear without treatment and the length of time to symptom resolution is not tolerable for many patients ^[37]. Trials have compared ibuprofen alone to antibiotics and other therapies, hypothesizing that palliating symptoms will make the natural resolution of cystitis more tolerable and spare antibiotic usage ^[38]^[39]. While infection may resolve at similar rates when using ibuprofen compared to antibiotics, higher symptom burden and incidence of pyelonephritis are still consequences that require consideration ^[40].

These challenges elucidate the need for alternative therapies that provide symptomatic relief, have antipathogenic properties, and do not perpetuate recurrent infection. Investigations into the microbial diversity and population of the urobiome between healthy individuals and those with acute bacterial cystitis have prompted an interest in probiotic supplementation as a therapy for recurrent cystitis ^[41]. Several botanical and nutritional therapies, many of which originated in traditional medicine systems, have gained attention as promising alternative therapeutic models for cystitis. While most antibiotics employ a single pharmacologic mechanism to fight bacteria, botanicals generally contain a complex array of phytochemicals that have evolved in response to diverse threats, possibly yielding robustness against the development of targeted resistance ^[42]. Finally, urogenital hygiene and hydration are significant yet clinically undervalued contributors to urinary tract health that can be leveraged through behavioral interventions ^[43]. Altogether, these alternative approaches may be combined to target several mechanisms of action and address compounding etiologies for both acute and recurrent/chronic cystitis (see Table 1).

Table 1. Whole-Person Approach to Uncomplicated UTI and Urobiome Health.

Therapy	Strategy	Mechanism	References
Lactobacillus spp. (Probiotics)	Decrease pathogenic bacteria by competing with pathogenic microbes for nutrients and space; May provide healthy microbial metabolites.	Urobiome support Anti-adhesion Anti-inflammatory	^[44]^[45]^[46]^[47]^[48]^[49]^[50]
D-mannose	Inhibits pathological bacterial adhesion to uro-epithelium.	Anti-adhesion	^[51]^[52]^[53]^[54]^[55]^[56]
Cranberry	Increases growth of beneficial bacteria and decreases growth of pathogenic bacteria.	Urobiome support Anti-adhesion Anti-septic Anti-inflammatory Diuresis	^[57]^[58]^[59]^[60]^[61]^[62]^[63]^[64]^[65]^[66]^[67]^[68]^[69]^[70]
Arctostaphylos uva-ursi	Increases urine flow to decrease pathogenic bacteria.	Anti-septic Anti-inflammatory Diuresis	^[71]^[72]^[73]^[74]^[75]^[76]^[77]^[78]
Sexual hygiene & Contraception choice	Slow contamination.	Anti-contamination pH level maintenance	^[79]^[80]^[81]
Hydration	Increases urine flow to clear pathogenic bacteria.	Urobiome support Anti-contamination Diuresis pH level maintenance	^[82]
Diet	Increase growth of beneficial bacteria; slow contamination; decrease growth and adhesion of pathogens	Anti-contamination Urobiome support Anti-inflammatory Anti-adhesion	^[83]^[84]^[85]^[86]^[87]^[88]^[89]^[90]^[91]

References

Harrabi, H. Uncomplicated urinary tract infection. N. Engl. J. Med. 2012, 367, 185.
Shapiro, D.J.; Hicks, L.A.; Pavia, A.T.; Hersh, A.L. Antibiotic prescribing for adults in ambulatory care in the USA, 2007–09. J. Antimicrob. Chemother. 2014, 69, 234–240.
Malik, R.D.; Wu, Y.R.; Zimmern, P.E. Definition of Recurrent Urinary Tract Infections in Women: Which One to Adopt? Female Pelvic. Med. Reconstr. Surg. 2018, 24, 424–429.
Langford, B.J.; Brown, K.A.; Diong, C. The Benefits and Harms of Antibiotic Prophylaxis for Urinary Tract Infection in Older Adults. Clin. Infect. Dis. 2021, 73, e782–e791.
Wright, S.W.; Wrenn, K.D.; Haynes, M.L. Trimethoprim-sulfamethoxazole resistance among urinary coliform isolates. J. Gen. Intern. Med. 1999, 14, 606–609.
Kristiansen, J.E. The antimicrobial activity of non-antibiotics. Report from a congress on the antimicrobial effect of drugs other than antibiotics on bacteria, viruses, protozoa, and other organisms. APMIS Suppl. 1992, 30, 7–14.
Gupta, K.; Hooton, T.M.; Naber, K.G.; Wult, B.; Colgan, R.; Miller L., G.; Moran, G.J.; Nicolla, L.E.; Raz, R.; Schaeffer, A.J.; et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin. Infect. Dis. 2011, 52, e103–e120.
Bryce, A.; Hay, A.D.; Lane, I.F.; Thornton, H.V.; Wootton, M.; Costelloe, C. Global prevalence of antibiotic resistance in paediatric urinary tract infections caused by Escherichia coli and association with routine use of antibiotics in primary care: Systematic review and meta-analysis. BMJ 2016, 352, i939.
Sanchez, G.V.; Master, R.N.; Karlowsky, J.A.; Bordon, J.M. In vitro antimicrobial resistance of urinary Escherichia coli isolates among U.S. outpatients from 2000 to 2010. Antimicrob. Agents Chemother. 2012, 56, 2181–2183.
Dalhoff, A. Resistance surveillance studies: A multifaceted problem—the fluoroquinolone example. Infection 2012, 40, 239–262.
Deshpande, A.; Pasupuleti, V.; Thota, P.; Pant, C.; Rolston, D.K.; Sferra, T.J.; Hernadez, A.V.; Donskey, C.J. Community-associated Clostridium difficile infection and antibiotics: A meta-analysis. J. Antimicrob. Chemother. 2013, 68, 1951–1961.
Simmering, J.E.; Tang, F.; Cavanaugh, J.E.; Polgreen, L.A.; Polgreen, P.M. The Increase in Hospitalizations for Urinary Tract Infections and the Associated Costs in the United States, 1998-2011. Open Forum Infect. Dis. 2017, 4, ofw281.
Gupta, K.; Hooton, T.M.; Roberts, P.L.; Stamm, W.E. Patient-initiated treatment of uncomplicated recurrent urinary tract infections in young women. Ann. Intern. Med. 2001, 135, 9–16.
Wiley, Z.; Jacob, J.T.; Burd, E.M. Targeting Asymptomatic Bacteriuria in Antimicrobial Stewardship: The Role of the Microbiology Laboratory. J. Clin. Microbiol. 2020, 58, e00518-18.
Nicolle, L.E.; Gupta, K.; Bradley, S.F.; Colgan, R.; DeMuri, G.P.; Drekonja, D.; Eckert, L.O.; Geerlings, S.E.; Koves, B.; Hooton, T.M.; et al. Clinical Practice Guideline for the Management of Asymptomatic Bacteriuria: 2019 Update by the Infectious Diseases Society of America. Clin. Infect. Dis. 2019, 68, e83–e110.
Hagberg, L.; Engberg, I.; Freter, R.; Lam, J.; Olling, S.; Svanborg Eden, C. Ascending, unobstructed urinary tract infection in mice caused by pyelonephritogenic Escherichia coli of human origin. Infect. Immun. 1983, 40, 273–283.
Svanborg Edén, C.; Hagberg, L.; Leffler, H.; Lomberg, H. Recent progress in the understanding of the role of bacterial adhesion in the pathogenesis of urinary tract infection. Infection 1982, 10, 327–332.
Storme, O.; Tirán Saucedo, J.; Garcia-Mora, A.; Dehesa-Dávila, M.; Naber, K.G. Risk factors and predisposing conditions for urinary tract infection. Ther. Adv. Urol. 2019, 11, 1756287218814382.
Sabih, A.; Leslie, S.W. Complicated Urinary Tract Infections. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2022; Available online: https://www-ncbi-nlm-nih-gov.offcampus.lib.washington.edu/books/NBK436013/ (accessed on 12 August 2021).
Leue, C.; Kruimel, J.; Vrijens, D.; Masclee, A.; van Os, J.; van Koeveringe, G. Functional urological disorders: A sensitized defence response in the bladder-gut-brain axis. Nat. Rev. Urol. 2017, 14, 153–163.
Markowitz, M.A.; Wood, L.N.; Raz, S.; Miller, L.G.; Haake, D.A.; Kim, J.H. Lack of uniformity among United States recommendations for diagnosis and management of acute, uncomplicated cystitis. Int. Urogynecol. J. 2019, 30, 1187–1194.
Jung, C.; Brubaker, L. The etiology and management of recurrent urinary tract infections in postmenopausal women. Climacteric 2019, 22, 242–249.
Cortes-Penfield, N.W.; Trautner, B.W.; Jump, R.L.P. Urinary Tract Infection and Asymptomatic Bacteriuria in Older Adults. Infect. Dis. Clin. N. Am. 2017, 31, 673–688.
Köves, B.; Wullt, B. The Roles of the Host and the Pathogens in Urinary Tract Infections. Eur. Urol. Suppl. 2016, 15, 88–94.
Wu, J.; Hayes, B.W.; Phoenix, C.; Macias, G.S.; Miao, Y.; Choi, H.W.; Hughes Jr., F.M.; Purves, J.T.; Reinhardt, R.L.; Abraham, S.N. A highly polarized TH2 bladder response to infection promotes epithelial repair at the expense of preventing new infections. Nat. Immunol. 2020, 21, 671–683.
Hilt, E.E.; McKinley, K.; Pearce, M.M.; Rosenfeld, A.B.; Zilliox, M.J.; Mueller, E.R.; Brubaker, L.; Gai, X.; Wolfe, A.J.; Schreckenberger, P.C. Urine is not sterile: Use of enhanced urine culture techniques to detect resident bacterial flora in the adult female bladder. J. Clin. Microbiol. 2014, 52, 871–876.
Pearce, M.M.; Hilt, E.E.; Rosenfeld, A.B.; Zilliox, M.J.; Thomas-White, K.; Fok, C.; Kliethermes, S.; Schreckenberger, P.C.; Brubaker, L.; Gai, X.; et al. The female urinary microbiome: A comparison of women with and without urgency urinary incontinence. mBio 2014, 5, e01283-14.
O’Brien, V.P.; Hannan, T.J.; Yu, L.; Livny, J.; Roberson, E.D.O.; Schwartz, D.J.; Souza, S.; Mendelsohn, C.L.; Colonna, M.; Lewis, A.L.; et al. A mucosal imprint left by prior Escherichia coli bladder infection sensitizes to recurrent disease. Nat. Microbiol. 2016, 2, 16196.
Whiteside, S.A.; Razvi, H.; Dave, S.; Reid, G.; Burton, J.P. The microbiome of the urinary tract—a role beyond infection. Nat. Rev. Urol. 2015, 12, 81–90.
Ursell, L.K.; Metcalf, J.L.; Parfrey, L.W.; Knight, R. Defining the human microbiome. Nutr. Rev. 2012, 70 (Suppl. 1), S38–S44.
Goneau, L.W.; Yeoh, N.S.; MacDonald, K.W.; Cadieux, P.A.; Burton, J.P.; Razvi, H.; Reid, G. Selective target inactivation rather than global metabolic dormancy causes antibiotic tolerance in uropathogens. Antimicrob. Agents Chemother. 2014, 58, 2089–2097.
Waller, T.A.; Pantin, S.A.L.; Yenior, A.L.; Pujalte, G.G.A. Urinary Tract Infection Antibiotic Resistance in the United States. Prim. Care 2018, 45, 455–466.
Meštrović, T.; Matijašić, M.; Perić, M.; Paljetak, H.C.; Barešić, A.; Verbanac, D. The Role of Gut, Vaginal, and Urinary Microbiome in Urinary Tract Infections: From Bench to Bedside. Diagnostics 2020, 11, 7.
Visconti, A.; Le Roy, C.I.; Rosa, F.; Rossi, N.; Martin, T.C.; Mohney, R.P.; Li, W.; de Rinaldis, E.; Bell, J.T.; Venter, J.C.; et al. Interplay between the human gut microbiome and host metabolism. Nat. Commun. 2019, 10, 4505.
Stapleton, A.E. Urinary tract infection pathogenesis: Host factors. Infect. Dis. Clin. N. Am. 2014, 28, 149–159.
Knottnerus, B.J.; Geerlings, S.E.; Moll van Charante, E.P.; ter Riet, G. Women with symptoms of uncomplicated urinary tract infection are often willing to delay antibiotic treatment: A prospective cohort study. BMC Fam. Pract. 2013, 14, 71.
Christiaens, T.C.; De Meyere, M.; Verschraegen, G.; Peersman, W.; Heytens, S.; De Maeseneer, J.M. Randomised controlled trial of nitrofurantoin versus placebo in the treatment of uncomplicated urinary tract infection in adult women. Br. J. Gen. Pract. 2002, 52, 729–734.
Little, P.; Moore, M.V.; Turner, S.; Rumsby, K.; Warner, G.; Lowes, J.A.; Smith, H.; Hawke, C.; Leydon, G.; Arscott, A.; et al. Effectiveness of five different approaches in management of urinary tract infection: Randomised controlled trial. BMJ 2010, 340, c199.
Ferry, S.A.; Holm, S.E.; Stenlund, H.; Lundholm, R.; Monsen, T.J. The natural course of uncomplicated lower urinary tract infection in women illustrated by a randomized placebo controlled study. Scand. J. Infect. Dis. 2004, 36, 296–301.
Gágyor, I.; Bleidorn, J.; Kochen, M.M.; Schmiemann, G.; Wegscheider, K.; Hummers-Pradier, E. Ibuprofen versus fosfomycin for uncomplicated urinary tract infection in women: Randomised controlled trial. BMJ 2015, 351, h6544.
Wojciuk, B.; Salabura, A.; Grygorcewicz, B.; Kędzierska, K.; Ciechanowski, K.; Dolęgowska, B. Urobiome: In Sickness and in Health. Microorganisms 2019, 7, 548.
Anand, U.; Jacobo-Herrera, N.; Altemimi, A.; Lakhssassi, N. A Comprehensive Review on Medicinal Plants as Antimicrobial Therapeutics: Potential Avenues of Biocompatible Drug Discovery. Metabolites 2019, 9, 258.
McCollum, B.J.; Garigan, T.; Earwood, J. PURL: Can drinking more water prevent urinary tract infections? J. Fam. Pract. 2020, 69, E19–E20.
Beerepoot, M.; Geerlings, S. Non-Antibiotic Prophylaxis for Urinary Tract Infections. Pathogens 2016, 5, 36.
Beerepoot, M.A.; ter Riet, G.; Nys, S.; van der Wal, W.M.; de Borgie, C.A.J.M.; Reijke, T.M.; Prins, J.M.; Koeijers, J.; Verbon, A.; Stobberingh, E.; et al. Lactobacilli vs antibiotics to prevent urinary tract infections: A randomized, double-blind, noninferiority trial in postmenopausal women. Arch. Intern. Med. 2012, 172, 704–712.
Mueller, E.R.; Wolfe, A.J.; Brubaker, L. Female urinary microbiota. Curr. Opin. Urol. 2017, 27, 282–286.
Stapleton, A.E.; Au-Yeung, M.; Hooton, T.M.; Fredricks, D.N.; Roberts, P.L.; Czaja, C.A.; Yarova-Yarovaya, Y.; Fiedler, T.; Cox, M.; Stamm, W.E. Randomized, placebo-controlled phase 2 trial of a Lactobacillus crispatus probiotic given intravaginally for prevention of recurrent urinary tract infection. Clin. Infect. Dis. 2011, 52, 1212–1217.
Reid, G.; Charbonneau, D.; Erb, J.; Kochanowski, B.; Beuerman, D.; Poehner, R.; Bruce, A.W. Oral use of Lactobacillus rhamnosus GR-1 and L. fermentum RC-14 significantly alters vaginal flora: Randomized, placebo-controlled trial in 64 healthy women. FEMS Immunol. Med. Microbiol. 2003, 35, 131–134.
Schwenger, E.M.; Tejani, A.M.; Loewen, P.S. Probiotics for preventing urinary tract infections in adults and children. Cochrane Database Syst Rev. 2015, 2015, CD008772.
Markowiak, P.; Śliżewska, K. Effects of Probiotics, Prebiotics, and Synbiotics on Human Health. Nutrients 2017, 9, 1021.
Klein, T.; Abgottspon, D.; Wittwer, M.; Rabbani, S.; Herold, J.; Jiang, X.; Kleeb, S.; Lüthi, C.; Scharenberg, M.; Bezençon, J.; et al. FimH antagonists for the oral treatment of urinary tract infections: From design and synthesis to in vitro and in vivo evaluation. J. Med. Chem. 2010, 53, 8627–8641.
Domenici, L.; Monti, M.; Bracchi, C.; Giorgini, M.; Colagiovanni, V.; Muzii, L.; Panici, P.B. D-mannose: A promising support for acute urinary tract infections in women. A pilot study. Eur. Rev. Med. Pharmacol. Sci. 2016, 20, 2920–2925.
Lenger, S.M.; Bradley, M.S.; Thomas, D.A.; Bertolet, M.H.; Lowder, J.L.; Sutcliffe, S. D-mannose vs other agents for recurrent urinary tract infection prevention in adult women: A systematic review and meta-analysis. Am. J. Obstet. Gynecol. 2020, 223, 265.e1–265.e13.
De Nunzio, C.; Bartoletti, R.; Tubaro, A.; Simonato, A.; Ficarra, V. Role of D-Mannose in the Prevention of Recurrent Uncomplicated Cystitis: State of the Art and Future Perspectives. Antibiotics 2021, 10, 373.
Scribano, D.; Sarshar, M.; Prezioso, C. d-Mannose Treatment neither Affects Uropathogenic Escherichia coli Properties nor Induces Stable FimH Modifications. Molecules 2020, 25, 316.
Cooper, T.E.; Teng, C.; Howell, M.; Teixeira-Pinto, A.; Tong, A.; Wong, G. D-mannose for preventing and treating urinary tract infections. Cochrane Database Syst Rev. 2020, 2020, CD013608.
Feliciano, R.P.; Meudt, J.J.; Shanmuganayagam, D.; Krueger, C.G.; Reed, J.D. Ratio of “A-type” to “B-type” proanthocyanidin interflavan bonds affects extra-intestinal pathogenic Escherichia coli invasion of gut epithelial cells. J. Agric. Food Chem. 2014, 62, 3919–3925.
Huang, Y.; Nikolic, D.; Pendland, S.; Doyle, B.J.; Locklear, T.D.; Mahady, G.B. Effects of cranberry extracts and ursolic acid derivatives on P-fimbriated Escherichia coli, COX-2 activity, pro-inflammatory cytokine release and the NF-kappabeta transcriptional response in vitro. Pharm. Biol. 2009, 47, 18–25.
Vostalova, J.; Vidlar, A.; Simanek, V.; Galandakova, A.; Kosina, P.; Vacek, J.; Vrbkova, J.; Zimmermann, B.F.; Ulrickova, J.; Student, V. Are High Proanthocyanidins Key to Cranberry Efficacy in the Prevention of Recurrent Urinary Tract Infection? Phytother. Res. 2015, 29, 1559–1567.
Özcan, E.; Sun, J.; Rowley, D.C.; Sela, D.A. A Human Gut Commensal Ferments Cranberry Carbohydrates To Produce Formate. Appl. Environ. Microbiol. 2017, 83, e01097-17.
Anhê, F.F.; Roy, D.; Pilon, G.; Dudonné, S.; Matamoros, S.; Varin, T.V.; Garofalo, C.; Moine, Q.; Desjardins, Y.; Levy, E.; et al. A polyphenol-rich cranberry extract protects from diet-induced obesity, insulin resistance and intestinal inflammation in association with increased Akkermansia spp. population in the gut microbiota of mice. Gut 2015, 64, 872–883.
Straub, T.J.; Chou, W.-C.; Manson, A.L.; Schreiber IV, H.L.; Walker, B.J.; Desjardins, C.A.; Chapman, S.B.; Kaspar, K.L.; Kahsai, O.J.; Traylor, E.; et al. Limited effects of long-term daily cranberry consumption on the gut microbiome in a placebo-controlled study of women with recurrent urinary tract infections. BMC Microbiol. 2021, 21, 53.
Valles-Colomer, M.; Falony, G.; Darzi, Y.; Tigchelaar, E.F.; Wang, J.; Tito, R.Y.; Schiweck, C.; Kurilshikov, A.; Joossens, M.; Wijmenga, C.; et al. The neuroactive potential of the human gut microbiota in quality of life and depression. Nat. Microbiol. 2019, 4, 623–632.
Huang, S.; Mao, J.; Zhou, L.; Xiong, X.; Deng, Y. The imbalance of gut microbiota and its correlation with plasma inflammatory cytokines in pemphigus vulgaris patients. Scand. J. Immunol. 2019, 90, e12799.
Degnan, P.H.; Taga, M.E.; Goodman, A.L. Vitamin B12 as a modulator of gut microbial ecology. Cell Metab. 2014, 20, 769–778.
Rowley, C.A.; Kendall, M.M. To B12 or not to B12: Five questions on the role of cobalamin in host-microbial interactions. PLoS Pathog. 2019, 15, e1007479.
Gonyar, L.A.; Kendall, M.M. Ethanolamine and choline promote expression of putative and characterized fimbriae in enterohemorrhagic Escherichia coli O157:H7. Infect. Immun. 2014, 82, 193–201.
Yarbrough, M.L.; Briden, K.E.; Mitsios, J.V.; Weindel, A.L.; Terrill, C.M.; Hunstad, D.A.; Dietzen, D.J. Mass spectrometric measurement of urinary kynurenine-to-tryptophan ratio in children with and without urinary tract infection. Clin. Biochem. 2018, 56, 83–88.
Fu, Z.; Liska, D.; Talan, D.; Chung, M. Cranberry Reduces the Risk of Urinary Tract Infection Recurrence in Otherwise Healthy Women: A Systematic Review and Meta-Analysis. J. Nutr. 2017, 147, 2282–2288.
Bruyère, F.; Azzouzi, A.R.; Lavigne, J.-P.; Droupy, S.; Coloby, P.; Game, X.; Karsenty, G.; Issartel, B.; Ruffion, A.; Misrai, V.; et al. A multicenter, randomized, placebo-controlled study evaluating the efficacy of a combination of Propolis and cranberry (Vaccinium macrocarpon) (DUAB®) in preventing low urinary tract infection recurrence in women complaining of recurrent cystitis. Urol. Int. 2019, 103, 41–48.
Sticher, O.; Soldati, F.; Lehmann, D. Hochleistungsflüssigchromotographische Trennung und quantitative Bestimmung von Arbutin, Methylarbutin, Hydrochinon und Hydrochinonmonomethylaether in Arctostaphylos-, Bergenia-, Calluna- und Vaccinium Arten . Planta Med. 1979, 35, 253–261.
Żbikowska, B.; Franiczek, R.; Sowa, A.; Polukord, G.; Krzyżanowska, B.; Sroka, Z. Antimicrobial and Antiradical Activity of Extracts Obtained from Leaves of Five Species of the Genus Bergenia: Identification of Antimicrobial Compounds. Microb. Drug Resist. 2017, 23, 771–780.
Ma, C.; He, N.; Zhao, Y.; Xia, D.; Wei, J.; Kang, W. Antimicrobial Mechanism of Hydroquinone. Appl. Biochem. Biotechnol. 2019, 189, 1291–1303.
Zhang, B.; Zeng, M.; Li, B.; Kan, Y.; Wang, S.; Cao, B.; Huang, Y.; Zheng, X.; Feng, W. Arbutin attenuates LPS-induced acute kidney injury by inhibiting inflammation and apoptosis via the PI3K/Akt/Nrf2 pathway. Phytomedicine 2021, 82, 153466.
Madić, V.; Petrović, A.; Jušković, M.; Jugović, D.; Djordjević, L.; Stojanović, G.; Vasiljević, P. Polyherbal mixture ameliorates hyperglycemia, hyperlipidemia and histopathological changes of pancreas, kidney and liver in a rat model of type 1 diabetes. J. Ethnopharmacol. 2021, 265, 113210.
Jurica, K.; Benković, V.; Sikirić, S.; Karačonji, I.B.; Kopjar, N. The effects of strawberry tree (Arbutus unedo L.) water leaf extract and arbutin upon kidney function and primary DNA damage in renal cells of rats. Nat. Prod. Res. 2020, 34, 2354–2357.
Jurica, K.; Brčić Karačonji, I.; Mikolić, A.; Milojković-Opsenica, D.; Benković, V.; Kopjar, N. In vitro safety assessment of the strawberry tree (Arbutus unedo L.) water leaf extract and arbutin in human peripheral blood lymphocytes. Cytotechnology 2018, 70, 1261–1278.
Genovese, C.; Davinelli, S.; Mangano, K.; Tempera, G.; Nicolosi, D.; Corsello, S.; Vergalito, F.; Tartaglia, E.; Scapagnini, G.; Di Marco, R. Effects of a new combination of plant extracts plus d-mannose for the management of uncomplicated recurrent urinary tract infections. J. Chemother. 2018, 30, 107–114.
Czaja, C.A.; Stamm, W.E.; Stapleton, A.E.; Roberts, P.L.; Hawn, T.R.; Scholes, D.; Samadpour, M.; Hultgren, S.J.; Hooton, T.M. Prospective cohort study of microbial and inflammatory events immediately preceding Escherichia coli recurrent urinary tract infection in women. J. Infect. Dis. 2009, 200, 528–536.
Riepl, M. Compounding to Prevent and Treat Dysbiosis of the Human Vaginal Microbiome. Int. J. Pharm. Compd. 2018, 22, 456–465.
Hooton, T.M.; Fihn, S.D.; Johnson, C.; Roberts, P.L.; Stamm, W.E. Association between bacterial vaginosis and acute cystitis in women using diaphragms. Arch. Intern. Med. 1989, 149, 1932–1936.
Hooton, T.M.; Vecchio, M.; Iroz, A.; Tack, I.; Dornic, Q.; Seksek, I.; Lotan, Y. Effect of Increased Daily Water Intake in Premenopausal Women With Recurrent Urinary Tract Infections: A Randomized Clinical Trial. JAMA Intern. Med. 2018, 178, 1509–1515.
Kontiokari, T.; Laitinen, J.; Järvi, L.; Pokka, T.; Sundqvist, K.; Uhari, M. Dietary factors protecting women from urinary tract infection. Am. J. Clin. Nutr. 2003, 77, 600–604.
Vincent, C.; Boerlin, P.; Daignault, D.; Dozois, C.M.; Dutil, L.; Galankis, C.; Reid-Smith, R.J.; Tellier, P.P.; Tellis, P.A.; Ziebell, K.; et al. Food reservoir for Escherichia coli causing urinary tract infections. Emerg. Infect. Dis. 2010, 16, 88–95.
Jakobsen, L.; Kurbasic, A.; Skjøt-Rasmussen, L.; Ejrnæs, K.; Porsbo, L.J.; Pedersen, K.; Jensen, L.B.; Emborg, H.D.; Agersø, Y.; Olsen, K.E.P.; et al. Escherichia coli isolates from broiler chicken meat, broiler chickens, pork, and pigs share phylogroups and antimicrobial resistance with community-dwelling humans and patients with urinary tract infection. Foodborne Pathog. Dis. 2010, 7, 537–547.
Mulder, M.; Kiefte-de Jong, J.C.; Goessens, W.H.F.; de Visser, H.; Ikram, M.A.; Verbon, A.; Stricker, B.H. Diet as a risk factor for antimicrobial resistance in community-acquired urinary tract infections in a middle-aged and elderly population: A case-control study. Clin. Microbiol. Infect. 2019, 25, 613–619.
Chen, Y.C.; Chang, C.C.; Chiu, T.H.T.; Lin, M.N.; Lin, C.L. The risk of urinary tract infection in vegetarians and non-vegetarians: A prospective study. Sci. Rep. 2020, 10, 906.
Makki, K.; Deehan, E.C.; Walter, J.; Bäckhed, F. The Impact of Dietary Fiber on Gut Microbiota in Host Health and Disease. Cell Host Microbe 2018, 23, 705–715.
Daïen, C.I.; Pinget, G.V.; Tan, J.K.; Macia, L. Detrimental Impact of Microbiota-Accessible Carbohydrate-Deprived Diet on Gut and Immune Homeostasis: An Overview. Front. Immunol. 2017, 8, 548.
Jones-freeman, B.; Chonwerawong, M.; Marcelino, V.R.; Deshpande, A.V.; Forster, S.C.; Starkey, M.R. The microbiome and host mucosal interactions in urinary tract diseases. Mucosal Immunol. 2021, 14, 779–792.
McDonald, D.; Hyde, E.; Debelius, J.W.; Morton, J.T.; Gonzalez, A.; Ackermann, G.; Aksenov, A.A.; Behsaz, B.; Brennan, C.; Chen, Y.; et al. American Gut: An Open Platform for Citizen Science Microbiome Research. mSystems 2018, 3, e00031-18.

© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.

Upload a video for this entry

Information

Subjects: Infectious Diseases; Urology & Nephrology; Integrative & Complementary Medicine

Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :

Luciano Garofalo

View Times: 411

Update Date: 18 Feb 2022

Table of Contents

Video Upload Options

Confirm