Bioyitech’s Lacticaseibacillus paracasei X11 Scientific Trials on the Intervention of Hyperuricemia
Probiotics RESEARCH & DEVELOPMENT
【Experimental Methods】
A randomized, controlled trial was conducted, and specific pathogen-free mice were randomly divided into 4 groups: the control group (CON), the model group (MOD), the probiotic group (X11), and the active drug control group (ADC).
The establishment of the HUA model is shown in Figure 1. The CON group was fed with normal feed and water, while the other groups were fed with high-purine feed (containing yeast extract 400 g/kg, ribonucleic acid 20 g/kg, and fructose water). To induce HUA, mice were intraperitoneally injected with potassium oxonate 400 mg/kg dissolved in 0.5% CMC-Na solution for 4 weeks.
After successful modeling, gavage administration was initiated at 10 ml/kg body weight. The CON and MOD groups were given 0.85% NaCl, the X11 group was given 109 CFU/ml *Lacticaseibacillus Paracasei* X11, and the ADC group was given 42 mg/kg allopurinol (ALLO). Blood was collected from the mice's orbital veins on days 7, 21, and 35. Liver, kidney, and intestinal tissues were collected and stored at −80°C until use.
【Experimental Results】
1. Bioyitech *Lacticaseibacillus paracasei* X11 can reduce the level of uric acid in the body by inhibiting the activity of hepatic uric acid synthesis enzymes (ADA, hepatic adenosine deaminase, and XOD, hepatic xanthine oxidase), with no significant difference compared to the drug allopurinol!
To evaluate the effect of Lacticaseibacillus paracasei X11 on the activity of UA metabolic enzymes in mice, we measured the levels of ADA and XOD in mouse livers, and the results are shown in the figure below. It was observed that, compared with the CON group, the enzyme activities of ADA and XOD in the MOD group were significantly increased (p < 0.05). The enzyme activities of ADA and XOD in the X11 group were inhibited, which was consistent with the ADC group. The enzyme activities of ADA and XOD were down-regulated by 30.59% and 33.69%, respectively (p < 0.05), indicating that *Lacticaseibacillus paracasei* X11 may reduce UA levels by inhibiting the activity of hepatic UA synthesis enzymes.
2. X11 has potential therapeutic effects by reducing the serum biochemical indicators of HUA and avoiding the side effects of the clinical drug ALLO.
After 14 days of gavage, the administration effects were observed as shown in the figure below. *Lacticaseibacillus paracasei* X11 can:
Reduce serum uric acid by 52.45%, reduce serum urea nitrogen by 26.75%, reduce serum creatinine by 47.54%, and reduce serum XOD by 44.60%.
3. X11 enhances the "acid excretion" level of the kidneys.
Renal reabsorption transporters and excretion transporters play an important role in mediating UA excretion.
To study the effects of *Lacticaseibacillus paracasei* X11 on the expression levels of the mouse renal reabsorption transporters GLUT9, URAT1, and the excretion transporter NPT1 involved in UA metabolism. As shown in the figure below, compared with the CON group, the expression of URAT1 and NPT1 in the MOD group showed no significant changes. However, the GLUT9 level in the MOD group was significantly increased (p < 0.05). Compared with the MOD group, the expression of the reabsorption transporters GLUT9 and URAT1 in the X11 group decreased by 24.39% and 24.69%, respectively (p < 0.05), while the expression of the excretion transporter increased by 7.3% (p < 0.05).
4. X11 is superior to allopurinol in improving liver and kidney damage caused by excessive purine intake!
As shown in the figure below, normal liver cell morphology was observed in the CON group, and the liver cell morphology in the MOD group was swollen. Cytoplasmic turbidity was severe, and lipid droplet deposition was obvious in the MOD group, which was alleviated in the X11 and ADC groups. However, the glomeruli in the MOD and ADC groups were atrophic and deformed, and the renal tubules were significantly dilated compared to the CON group. *Lacticaseibacillus paracasei* X11 can improve the above adverse symptoms and reduce inflammatory cell infiltration. The villi in the MOD and ADC groups were shortened and sparsely distributed. In contrast, the villi length and crypt depth in the X11 group were improved, and the damage caused by lipid infiltration and UA and ALLO was alleviated.
5. X11 can effectively restore the intestinal microbial diversity in mice with hyperuricemia.
To explore the effect of Lacticaseibacillus paracasei X11 on the intestinal microbiota of mice, 16S rRNA MiSeq sequencing was used to analyze the fecal microbiota of mice. The results showed that the intestinal microbial diversity in the MOD group decreased, and the intestinal microbial diversity was moderately restored after treatment with *Lacticaseibacillus paracasei* X11.
【Experimental Conclusion】
The probiotic Lacticaseibacillus paracasei X11 can effectively inhibit the production of purine substances, repair liver and kidney damage caused by excessive purine intake while strengthening renal acid excretion, and also has a significant inhibitory effect on pro-inflammatory factors in serum, liver, and kidneys. Moreover, it can well regulate the intestinal flora, improve the diversity of the intestinal flora, and maintain the healthy state of the intestinal flora.