RESUMO
Antibiotics can alter the gut microbiome (GMB), which may be associated with stone disease. We sought to determine the effect that antibiotics have on the GMB, urine ion excretion and stone formation in genetic hypercalciuric stone-forming (GHS) rats. 116th generation GHS rats were fed a fixed amount of a normal calcium (1.2%) and phosphate (0.65%) diet, and divided into three groups (n = 10): control (CTL) diet, or supplemented with ciprofloxacin (Cipro, 5 mg/day) or Bactrim (250 mg/day). Urine and fecal pellets were collected over 6, 12 and 18 weeks. Fecal DNA was amplified across the 16S rRNA V4 region. At 18 weeks, kidney stone formation was visualized by Faxitron and blindly assessed by three investigators. After 18 weeks, urine calcium and oxalate decreased with Bactrim compared to CTL and Cipro. Urine pH increased with Bactrim compared to CTL and Cipro. Urine citrate increased with Cipro compared to CTL and decreased by half with Bactrim. Calcification increased with Bactrim compared to CTL and Cipro. Increased microbial diversity correlated with decreased urinary oxalate in all animals (R = - 0.46, p = 0.006). A potential microbial network emerged as significantly associated with shifts in urinary pH. Bactrim and Cipro differentially altered the GMB of GHS rats. The Bactrim group experienced a decrease in urine calcium, increased CaP supersaturation and increased calcification. The GMB is likely a contributing factor to changes in urine chemistry, supersaturation and stone risk. Further investigation is required to fully understand the association between antibiotics, the GMB and kidney stone formation.
Assuntos
Antibacterianos/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Hipercalciúria/complicações , Cálculos Renais/etiologia , Administração Oral , Animais , Antibacterianos/administração & dosagem , Cálcio/metabolismo , Cálcio/urina , Ciprofloxacina/administração & dosagem , Ciprofloxacina/efeitos adversos , Modelos Animais de Doenças , Fezes/microbiologia , Humanos , Hipercalciúria/genética , Hipercalciúria/microbiologia , Hipercalciúria/urina , Cálculos Renais/diagnóstico , Cálculos Renais/urina , RNA Ribossômico 16S/genética , Ratos , Eliminação Renal , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem , Combinação Trimetoprima e Sulfametoxazol/efeitos adversosRESUMO
OBJECTIVE: We aimed to evaluate whether Ca(+2) utilization of intestinal flora (IF) has an effect on urinary excretion of Ca(+2) (UCaE) levels. MATERIALS AND METHODS: Fecal samples (0.1 g/mL) of children who underwent UCaE examination in the past year were implanted in broths. Labeled (45)Ca (5 muL) was added to the samples and incubated. From these samples, a 200-muL quantity was filtrated with a 0.45-micrometer membrane and was rinsed in 200 muL pure water. (45)Ca activity in the membrane was measured and defined as percent activity per bacteria ((45)Ca(act) %/CFU). Levels of aerobic and anaerobic (45)Ca(act) %/CFU and their correlations with UCaE were compared between hypercalciuric (Group I) and normocalciuric (Group II) patients. RESULTS: Levels of (45)Ca %/CFU were similar between groups (P > .05). Aerobic and anaerobic (45)Ca(act)%/CFU levels were not significantly correlated to UCaE, either in normocalciuric (P = .079, r = -0.503; P = .260, r = -0.420, stray mart respectively) or in hypercalciuric children (P = .509, r = 0.223; P = .623, r = -0.257, respectively). CONCLUSION: Similar (45)Ca(act)%/CFU levels in the 2 groups imply that calcium utilization of IF does not have a distinct effect on UCaE.
