Abstract

BackgroundLower urinary tract symptoms (LUTS) is the most common complication of diabetes. However, the underlying pathogenesis of cultured negative LUTS (cn-LUTS) in diabetic patients has not been well understood. Numerous evidence indicates that urinary dysbiosis is related to urologic disorders. We aim to study alterations of the urinary microbiota of cn-LUTS in type 2 diabetes (T2D) patients.MethodsFemale T2D patients and controls were recruited and requested to finish the American Urological Association Symptom Index. Mid-stream urine was collected for culturing and extracting DNA. Microbial diversity and composition were analyzed by targeting to 16S rDNA. Linear discriminant analysis effect size (LEfSe) was carried out to identify significantly different bacteria.Results32 female T2D patients and 26 controls were enrolled. No significant differences in alpha diversity were observed between patients and controls. However, statistically decreased richness (ACE index and Chao 1 index, 85.52(13.75, 204.84) vs. 129.82(63.89, 280.30) and 83.86(11.00, 210.77) vs. 125.19(62.00, 251.77), P = 0.005; Observed Species, 76(10, 175) vs. 98(54, 234), P = 0.011) and decreased species diversity (Shannon index, 1.37(0.04, 3.48) vs. 2.09(0.98, 3.43), P = 0.033; Simpson index, 0.46 (0.06, 0.99) vs. 0.23(0.07, 0.64), P = 0.029) were shown in moderate-to-severe LUTS group and high Hemoglobin A1c group, respectively. A significant difference of beta diversity was found between T2D patients and controls and T2D patients with different severity of cn-LUTS as well as the different level of Hemoglobin A1c. LEfSe revealed that 10 genera (e.g., Escherichia-Shigella and Klebsiella) were increased and 7 genera were decreasing in T2D patients, 3 genera (e.g., Escherichia-Shigella and Campylobacter) were increased and 16 genera (e.g., Prevotella) were reduced in moderate-to-severe LUTS group, 2 genera (Escherichia-Shigella and Lactobacillus) were over-represented and 10 genera (e.g., Prevotella) were under-represented in high Hemoglobin A1c group. Finally, Hemoglobin A1c was found positively correlated with the total score of the American Urological Association Symptom Index (r = 0.509, P = 0.003).ConclusionsUrinary dysbiosis may be related to cn-LUTS in female T2D patients. A better understanding of urinary microbiota in the development and progression of cn-LUTS in female T2D patients was necessary. The severity of cn-LUTS was correlated to hyperglycemia and chronic hyperglycemia might induce or promote cn-LUTS by influencing urinary microbiota.

Highlights

  • Lower urinary tract symptoms (LUTS) is the most common complication of diabetes

  • LUTS In order to detect the specific bacteria associated with the severity of LUTS, we studied whether the urinary microbial profile was different between type 2 diabetes (T2D) patients with no to mild LUTS (LS group, total American Urological Association Symptom Index (AUA-SI) score ≤ 7) and T2D patients with moderate to severe LUTS (HS group, total AUA-SI score > 7)

  • In this study, we describe the urinary microbiota in the female with and without T2D, female T2D patients with no to mild LUTS and moderate to severe LUTS as well as patients with low Hemoglobin A1c (HbA1c) and high HBA1c using 16S rDNA sequencing

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Summary

Introduction

Lower urinary tract symptoms (LUTS) is the most common complication of diabetes. The underlying pathogenesis of cultured negative LUTS (cn-LUTS) in diabetic patients has not been well understood. Most diabetic patients are likely suffering from LUTS without evidence of urinary tract infections (UTI), which are refractory and hardly benefit from the conventional treatment. For these patients, it is supposed that the potential pathogenesis of LUTS may be linked to polyuria, oxidative stress and autonomic neuropathy induced by chronic hyperglycemia [3]. The underlying pathogenesis of cultured negative LUTS (cn-LUTS) induced by diabetes has not been fully appreciated

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