Figure 1. Comparison between the without-pyuria and pyuria groups for the number of OTUs (A) and the Shannon diversity index (B) in T2D patients treated with SGLT2 inhibitor. ** p < 0.01.

Figure 2. A stacked histogram showing the relative abundance of 16S metagenomic sequences in the urine of T2D patients treated with SGLT2 inhibitors.

Figure 3. Pearson correlation coefficient heat map of mutual analysis between bacteria (genus or species) and clinical characteristics of 11 kinds. The magnitude of the R-value of the correlation analysis is displayed by color difference. * p < 0.05.

Table 1. Clinical characteristics of T2D patients treated with SGLT2 inhibitor.

Table 1. Clinical characteristics of T2D patients treated with SGLT2 inhibitor.

Without Pyuria (n = 4)Pyuria (n = 3)p ValueDuration of diabetes (y)9.75 ± 6.1214.33 ± 5.890.614Age (y)59 ± 5.759.66 ± 6.50.942Gender (female, n)13 Urine WBC > 1 cell (%)0%100%0.008 **eGFR (mL/min/1.73 m2) stage II (n)25%100%0.047 *UACR > 30 mg/g (%)0%33.3%0.212HbA1c (%)7.15 ± 0.26.7 ± 0.30.336FPG (mg/dL)141 ± 13.1116.33 ± 7.80.174TC (mg/dL)189.55 ± 24.9130.33 ± 4.40.097TG (mg/dL)137.25 ± 23.4130.33 ± 4.40.097HDL-C (mg/dL)49.5 ± 3.4243 ± 3.210.226LDL-C (mg/dL)122 ± 22.8477 ± 7.370.142Hypertension (%)50%66%0.723Insulin use (%)0%66%0.062Urinary tract infection history (%)0%66%0.062

Table 2. Bacteria identified in the urine of SGLT2-inhibitor-treated T2D patients using 16S metagenomics.

Table 2. Bacteria identified in the urine of SGLT2-inhibitor-treated T2D patients using 16S metagenomics.

GroupSample IDShannon
Diversity IndexNumber of Species Identified (OTUs)Top 5 Species12345 Ur1 1.542 718 Proteus
mirabilis Streptococcus agalactiae Corynebacteriaceae Escherichia-
Shigella Staphylococcus 47.08%46.27%1.87%0.68%0.65%Without pyuriaUr22.634688 Enterococcus faecalis Corynebacterium Veillonella Bifidobacterium dentium Escherichia-Shigella 45.20%16.76%13.46%8.37%6.07% Ur32.725996 Proteus
mirabilis Lactobacillus
gasseri Streptococcus
anginosus C. sp. NML 100378 Lactobacillus 33.46%29.58%16.29%5.90%4.77% Ur41.947652 Staphylococcus Enterococcus
faecalis Corynebacteriaceae Veillonella kroppenstedtii 48.98%30.39%11.01%5.49%1.52% Ur50.1261028 Escherichia-
Shigella Escherichia coli Bifidobacterium dentium C. pyruviciproducens ATCC BAA-1742 Staphylococcus 99.44%0.14%0.06%0.05%0.05%PyuriaUr60.339632 Escherichia-
Shigella Proteus mirabilis Enterococcus
faecalis Streptococcus agalactiae Staphylococcus 97.44%0.63%0.26%0.24%0.19% Ur70.276581 Escherichia-
Shigella Proteus mirabilis Lactobacillus Enterococcus faecalis Streptococcus agalactiae 97.80%0.42%0.63%0.18%0.14%