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| Metabolic syndrome and the urinary microbiome of patients undergoing percutaneous nephrolithotomy |
Ryan A. Dornbiera,Chirag P. Doshia,Shalin C. Desaia,*( ),Petar Bajica,Michelle Van Kuikena,Mark Khemmanib,Ahmer V. Farooqa,Larissa Breslera,Thomas M.T. Turka,Alan J. Wolfeb,Kristin G. Baldeaa
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aLoyola University Medical Center, Department of Urology, Maywood, IL, USA
bLoyola University Chicago, Department of Microbiology and Immunology, Maywood, IL, USA |
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Abstract Objective: To identify possible stone-promoting microbes, we compared the profiles of microbes grown from stones of patients with and without metabolic syndrome (MetS). The association between MetS and urinary stone disease is well established, but the exact pathophysiologic relationship remains unknown. Recent evidence suggests urinary tract dysbiosis may lead to increased nephrolithiasis risk. Methods: At the time of percutaneous nephrolithotomy, bladder urine and stone fragments were collected from patients with and without MetS. Both sample types were subjected to expanded quantitative urine culture (EQUC) and 16 S ribosomal RNA gene sequencing. Results: Fifty-seven patients included 12 controls (21.1%) and 45 MetS patients (78.9%). Both cohorts were similar with respect to demographics and non-MetS comorbidities. No controls had uric acid stone composition. By EQUC, bacteria were detected more frequently in MetS stones (42.2%) compared to controls (8.3%) (p=0.041). Bacteria also were more abundant in stones of MetS patients compared to controls. To validate our EQUC results, we performed 16 S ribosomal RNA gene sequencing. In 12/16 (75.0%) sequence-positive stones, EQUC reliably isolated at least one species of the sequenced genera. Bacteria were detected in both “infectious” and “non-infectious” stone compositions. Conclusion: Bacteria are more common and more abundant in MetS stones than control stones. Our findings support a role for bacteria in urinary stone disease for patients with MetS regardless of stone composition.
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Received: 15 April 2022
Available online: 20 April 2024
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Corresponding Authors:
* E-mail address: kbaldea@lumc.edu (S.C. Desai).
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| Baseline patient demographic and medical characteristic | Total | Control | MetS | p-Value | | Samples collected, n | 57 | 12 | 45 | NA | | Age, median (range), year | 62.3 (31.1-83.0) | 62.3 (42.0-69.9) | 62.8 (31.1-83.0) | 0.660 | | Gender, n (%) | | | | 0.504 | | Female | 36 (63.2) | 9 (75.0) | 27 (60.0) | | | Male | 21 (36.8) | 3 (25.0) | 18 (40.0) | | | Race or ethnicity, n (%) | | | | 0.484 | | Caucasian | 47 (82.5) | 10 (83.3) | 37 (82.2) | | | African American | 1 (1.8) | 1 (8.3) | 0 | | | Hispanic | 6 (10.5) | 1 (8.3) | 5 (11.1) | | | Asian | 2 (3.5) | 0 | 2 (4.4) | | | Unknown | 1 (1.8) | 0 | 1 (2.2) | | | Height, mean±SD, cm | 167.8±11.2 | 164.7±7.8 | 168.6±11.8 | 0.250 | | Weight, mean±SD, kg | 95.4±27.0 | 78.5±31.9 | 99.8±24.0 | 0.011 | | Body mass index, mean±SD, kg/m2 | 33.9±9.5 | 28.9±11.7 | 35.2±8.5 | 0.036 | | MetS criteria, n (%) | | Blood pressure of >130/85 mmHg or one anti-hypertensive medication, n (%) | 46 (80.7) | 4 (33.3) | 42 (93.3) | <0.001 | | Waist circumference over 89 cm (women) or 102 cm (men)a,b | 25 (73.5) | 3 (33.3) | 22 (88.0) | 0.004 | | Fasting triglyceride level of >150 mg/dLb | 40 (71.4) | 2 (16.7) | 38 (86.3) | <0.001 | | Fasting HDL level of <50 mg/dL (women) or <40 mg/dL (men) or dyslipidemia treatmentb | 43 (76.8) | 4 (33.3) | 39 (88.6) | <0.001 | | Fasting glucose level of >100 mg/dL or diabetes treatment | 38 (66.7) | 2 (16.7) | 36 (80.0) | <0.001 | | Urologic history, n (%) | | Indwelling Foley catheter or suprapubic tube | 0 (0) | 0 | 0 | NA | | CIC | 0 (0) | 0 | 0 | NA | | Prior indwelling ureteral stent or nephrostomy tube | 9 (15.8) | 1 (8.3) | 8 (17.8) | 0.669 | | History of recurrent urinary tract infections | 13 (22.8) | 4 (33.3) | 9 (20.0) | 0.440 | | Prior medical stone prevention | 13 (22.8) | 2 (16.7) | 11 (24.4) | 0.713 | | Antibiotic use within 30 days (excluding prophylactic antibiotics) | 11 (19.3) | 1 (8.3) | 10 (22.2) | 0.426 | | Periprocedural antibiotic duration prior to specimen collection, n (%) | | | | 0.058 | | <3 h | 4 (7.0) | 2 (16.7) | 2 (4.4) | | | 3-<6 h | 2 (3.5) | 1 (8.3) | 1 (2.2) | | | 6-<12 h | 1 (1.8) | 1 (8.3) | 0 | | | 12-<24 h | 38 (66.7) | 7 (58.3) | 31 (68.9) | | | ≥24 h | 12 (21.1) | 1 (8.3) | 11 (24.4) | |
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Baseline patient demographics and medical characteristics comparing patients with MetS to controls.
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Growth of bacteria on expanded quantitative urine culture. (A) Urinary stone; (B) Bladder urine; (C) Stone chemical composition of the corresponding stone. The solid black line marks the division of control and metabolic syndrome patients. Each column above or below corresponds to the same patient.
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16 S rRNA gene sequencing of bladder and stone samples from controls and metabolic syndrome patients. The solid black vertical lines separate paired sampled.
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| Sample ID | Sample cohort | Stone culture genera | Stone sequence dominant genera | Bladder culture genera | Bladder sequence dominant genera | Bray-Curtis index between stone and bladder sequencing | | 5 | Control | NA | Proteus | NA | Escherichia, Aerococcus, Lactobacillus | 0.993 | | 41 | Control | Corynebacterium | Corynebacterium | Corynebacterium | Corynebacterium | 0.076 | | 3 | MetS | Proteus | Escherichia, Bifidobacterium | Escherichia | Escherichia, Proteus, Bifidobacterium | 0.410 | | 8 | MetS | NA | Veillonella | NA | Sneathia, Veillonella, Ureaplasma | 0.528 | | 11 | MetS | Aerococcus | Aerococcus | NA | Aerococcus, peptoniphilus, Anaerococcus | 0.379 | | 21 | MetS | Staphylococcus | Streptococcus | NA | Staphylococcus | 0.939 | | 23 | MetS | Aerococcus | Aerococcus | NA | NA | NA | | 26 | MetS | Staphylococcus | Staphylococcus | Staphylococcus | Staphylococcus | 0.041 | | 30 | MetS | Aerococcus, Proteus | Streptococcus, Aerococcus, Proteus | Actinomyces, Aerococcus, Enterococcus | Peptoniphilus | 0.326 | | 34 | MetS | Proteus | Proteus | NA | Proteus | 0.201 | | 40 | MetS | Proteus | Proteus, Klebsiella | NA | NA | NA | | 42 | MetS | Enterococcus | Enterococcus | NA | Enterococcus | 0.124 | | 50 | MetS | NA | Staphylococcus | Staphylococcus | Ureaplasma | 0.987 | | 52 | MetS | Proteus | Proteus | Aerococcus | Aerococcus, Proteus | 0.848 | | 53 | MetS | Aerococcus, Streptococcus | Streptococcus | NA | Aerococcus, Streptococcus, Fusobacterium | 0.552 | | 55 | MetS | Proteus | Proteus | NA | Lactobacillus | 0.905 |
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Comparison of stone culture, stone sequencing, bladder culture, and bladder sequencing genera from the same study participant.
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