Oral Acid Load Lowers Bacterial Burden and Elevates Urinary Proinflammatory Response in a Mouse Model of Urinary Tract Infection.

Abstract

AIM: Urinary tract infections (UTIs) are common and frequently caused by uropathogenic Escherichia coli (UPEC). Whether urinary pH has any influence on the development and progression of UTIs is still widely debated. In this study, we systematically address whether urinary pH affected progression and dissemination of UTIs. METHODS: To assess the effect of urine pH on the development of UTI in&#xa0;vivo, 8-10-week-old female Balb/cJRj mice were randomized to 100&#x2009;mM NHCl (acid-load), 100&#x2009;mM NaHCO(base-load), or demineralised water as drinking water intervention 24&#x2009;h before UTI was induced via installation of either UPEC or vehicle in the urinary bladder. RESULTS: Acid load lowered urinary pH by 0.8-1.0 pH points (p&#x2009;<&#x2009;0.0001), decreased [HCO] (p&#x2009;=&#x2009;0.0002), and increased [titratable acid] (TA, p&#x2009;=&#x2009;0.0007), [NH] (p&#x2009;<&#x2009;0.0001) and net acid concentration (NAC, p&#x2009;<&#x2009;0.0001), while base load raised urinary pH by 0.3-0.7 pH points (p&#x2009;=&#x2009;0.0154), increased [HCO] (p&#x2009;=&#x2009;0.0358), and decreased [TA] (p&#x2009;=&#x2009;0.0154), [NH] (p&#x2009;=&#x2009;0.0121) and NAC (p&#x2009;=&#x2009;0.0064). The UPEC infection did not affect urine acid/base parameters. Compared to control, acid load led to elevated urinary levels of tumor necrosis factor &#x3b1; (TNF-&#x3b1;), keratinocyte chemoattractant (KC), interleukin 1&#x3b2; (IL-1&#x3b2;) and IL-6, and reduced bacterial burden in urine (737.6&#x2009;&#xb1;&#x2009;1315.0&#x2009;CFU&#x2009;mLvs. 29.5&#x2009;&#xb1;&#x2009;53.3&#x2009;CFU&#x2009;mL, p&#x2009;=&#x2009;0.0030) and kidney (2.39&#x2009;&#xb1;&#x2009;5.94&#x2009;CFU&#x2009;mgvs. 0.06&#x2009;&#xb1;&#x2009;0.14&#x2009;CFU&#x2009;mg, p&#x2009;=&#x2009;0.0054). The opposite tendency was observed with base load (2204.0&#x2009;&#xb1;&#x2009;3135.0&#x2009;CFU&#x2009;mLurine, 2.23&#x2009;&#xb1;&#x2009;2.95&#x2009;CFU&#x2009;mgkidney). CONCLUSION: Thus, increased urine acid excretion reduced UPEC burden in urine and decreased risk of pyelonephritis while enhancing the urinary excretion of proinflammatory cytokines.