Effects of <i>S</i>. <i>thermophilus</i> IDCC 2201 on gut microbiota in SD rats with PO-induced hyperuricemia.

Distribution of gut microbiota at the (A) phylum and (B) order levels. (C) Taxonomic levels from the phylum to the genus (LDA score > 3.5, p S. thermophilus IDCC 2201 (1×108 CFU/ day); G6: L. plantarum CR1+S. thermophilus IDCC 2201 (1×108 CFU/ day); and G9: Allopurinol (50 mg/kg rat/day). A significant difference from G1 is denoted as * p † p †† p # p ## p < 0.01.</p

List of seven genome sequences analyzed in this study.

List of seven genome sequences analyzed in this study.</p

Overview of purine metabolism by HGPRT.

The purine metabolic system represents a pathway by which hypoxanthine and guanine can be salvaged by HGPRT. HGPRT serves to catalyze the salvage synthesis of IMP and GMP from the purine bases hypoxanthine and guanine. HGPRT also prevents the accumulation of substrates that are converted to uric acid.</p

List of strains used in this study.

This study evaluated 15 lactic acid bacteria with a focus on their ability to degrade inosine and hypo-xanthine—which are the intermediates in purine metabolism—for the management of hyperuricemia and gout. After a preliminary screening based on HPLC, Lactiplantibacillus plantarum CR1 and Lactiplantibacillus pentosus GZ1 were found to have the highest nucleoside degrading rates, and they were therefore selected for further characterization. S. thermophilus IDCC 2201, which possessed the hpt gene encoding hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and exhibited purine degradation, was also selected for further characterization. These three selected strains were examined in terms of their probiotic effect on lowering serum uric acid in a Sprague-Dawley (SD) rat model of potassium oxonate (PO)-induced hyperuricemia. Among these three strains, the level of serum uric acid was most reduced by S. thermophilus IDCC 2201 (p S. thermophlilus IDCC 2201 led to a significant difference in gut microbiota composition compared to that in the group administered with PO-induced hyperuricemia. Moreover, intestinal short-chain fatty acids (SCFAs) were found to be significantly increased. Altogether, the results of this work indicate that S. thermophilus IDCC 2201 lowers uric acid levels by degrading purine-nucleosides and also restores intestinal flora and SCFAs, ultimately suggesting that S. thermophilus IDCC 2201 is a promising candidate for use as an adjuvant treatment in patients with hyperuricemia.</div

Real-time PCR standard curve for <i>S</i>. <i>thermophilus</i> IDCC 2201.

Real-time PCR standard curve for S. thermophilus IDCC 2201.</p

Inosine degradation analysis by HPLC.

This study evaluated 15 lactic acid bacteria with a focus on their ability to degrade inosine and hypo-xanthine—which are the intermediates in purine metabolism—for the management of hyperuricemia and gout. After a preliminary screening based on HPLC, Lactiplantibacillus plantarum CR1 and Lactiplantibacillus pentosus GZ1 were found to have the highest nucleoside degrading rates, and they were therefore selected for further characterization. S. thermophilus IDCC 2201, which possessed the hpt gene encoding hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and exhibited purine degradation, was also selected for further characterization. These three selected strains were examined in terms of their probiotic effect on lowering serum uric acid in a Sprague-Dawley (SD) rat model of potassium oxonate (PO)-induced hyperuricemia. Among these three strains, the level of serum uric acid was most reduced by S. thermophilus IDCC 2201 (p S. thermophlilus IDCC 2201 led to a significant difference in gut microbiota composition compared to that in the group administered with PO-induced hyperuricemia. Moreover, intestinal short-chain fatty acids (SCFAs) were found to be significantly increased. Altogether, the results of this work indicate that S. thermophilus IDCC 2201 lowers uric acid levels by degrading purine-nucleosides and also restores intestinal flora and SCFAs, ultimately suggesting that S. thermophilus IDCC 2201 is a promising candidate for use as an adjuvant treatment in patients with hyperuricemia.</div

Effects of <i>S</i>. <i>thermophilus</i> IDCC 2201 concentrations on the reduction of blood uric acid levels in hyperuricemia rats.

(A) Body weights (g). (B) Serum UA (mg/dL). On the 7th day of the test, 3 hours after administration of the test substance or the comparative substance, blood was collected from the animal’s jugular vein for measurement of the uric acid level. G1: normal group; G2: hyperuricemia group; G3: S. thermophilus IDCC 2201-SH (1×109 CFU/day); G4: S. thermophilus IDCC 2201-SM (1×108 CFU/day); G5: S. thermophilus IDCC 2201-SL (1×107 CFU/day). Data are presented in the form of mean ± standard deviation values (N = 8). Different symbols indicate statistically significant differences according to the results of statistical analysis using t-testing. †† p < 0.01 vs G1, * p < 0.05 vs G2.</p

SCFAs content in rat feces.

G1: normal group; G2: hyperuricemia group; G3: S. thermophilus IDCC 2201-SH (1×109 CFU/day). The mean ± standard deviation values (N = 8) are depicted by bars. Different symbols indicate statistically significant differences according to the results of statistical analysis using t-testing. †† p ††† p 1) ppm = μg/mL.</p

The effect of probiotics on the reduction of blood uric acid level in hyperuricemia rats.

(A) Schematic depiction of the po-induced hyperuricemia model. (B) Body weights (g). (C) Serum UA (mg/dL). On the last day of administration of the test substance, 3 hours after administration of the test substance or the comparative substance, blood was collected from the jugular vein of the rat, while the uric acid level was measured using a blood biochemical analyzer. G1: normal group; G2: hyperuricemia group; G3: L. plantarum CR1 (1×108 CFU/ day); G4: L. pentosus GZ1 (1×108 CFU/ day); G5: S. thermophilus IDCC 2201 (1×108 CFU/ day); G6: L. plantarum CR1+S. thermophilus IDCC 2201 (1×108 CFU/ day); G7: L. pentosus GZ1+ S. thermophilus IDCC 2201 (1×108 CFU/ day); G8: L. gasseri PA-3 (1×108 CFU/ day); and G9: Allopurinol (50 mg/kg rat/day). Data are presented as mean ± SD values (N = 6). Different symbols indicate significant differences according to the results of statistical analysis using a t-test. † p †† p ††† p < 0.001 vs G1, * p < 0.05, *** p < 0.001 vs G2.</p

Quantification of <i>S</i>. <i>thermophlius</i> IDCC 2201 in fecal samples of rats with hyperuricemia administered with <i>S</i>. <i>thermophilus</i> IDCC 2201, as analyzed by real-time PCR.

G1: normal group; G2: hyperuricemia group; G3: S. thermophilus IDCC 2201-SH (1×109 CFU/day). Data are presented in the form of mean ± standard deviation values (N = 8). Different symbols indicate statistically significant differences according to the results of statistical analysis using t-testing. n.s.: no significant difference between groups. ††† p < 0.001 vs G1, *** p < 0.001 vs G2.</p