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. 2022 Jul 6:13:940228.
doi: 10.3389/fimmu.2022.940228. eCollection 2022.

Lactobacillus paracasei X11 Ameliorates Hyperuricemia and Modulates Gut Microbiota in Mice

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Lactobacillus paracasei X11 Ameliorates Hyperuricemia and Modulates Gut Microbiota in Mice

Jiayuan Cao et al. Front Immunol. .

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Abstract

Hyperuricemia (HUA) is the presence of excessive uric acid (UA) in blood, which leads to an increased risk of chronic kidney disease and gout. Probiotics have the potential effect of alleviating HUA. The purpose of this study was to screen probiotics with UA-lowering activity and explore the underlying mechanism. The UA-lowering activity of 20 lactic acid bacteria strains was investigated in vitro, and the effect of candidate probiotics on UA metabolism was evaluated using the HUA Balb/c mouse model. The results showed that Lactobacillus paracasei X11 had excellent UA-lowering activity in vitro, which could degrade nucleotides and nucleosides completely within 30 min, and the degradation rates of purine and trioxypurine could reach 83.25% and 80.42%, respectively. In addition, oral administration of L. paracasei X11 could reduce serum UA by 52.45% and inhibit renal proinflammatory cytokine IL-1β by 50.69%, regulating adenosine deaminase (ADA), xanthine oxidase (XOD), and transporter expression (GLUT9, NPT1, and URAT1) to a normal level. Moreover, it could restore the ratio of Bacteroidetes to Firmicutes (Bac/Firm ratio) and showed a positive effect on the recovery of the intestinal microbiota. These findings provided fundamental information about the UA-lowering properties of probiotics, which suggested that L. paracasei X11 had the potential to be developed as a novel probiotic strain to ameliorate HUA.

Keywords: Lactobacillus paracasei X11; ameliorating; gut microbiota; hyperuricemia; uric acid-lowering.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Experimental chart of Lactobacillus paracasei X11 in treatment of HUA mice. HUA, hyperuricemia.
Figure 2
Figure 2
Histopathological analyses of H&E-stained liver and kidney sections (×200 magnification) and intense sections (×100 magnification) from mice.
Figure 3
Figure 3
Effects of Lactobacillus paracasei X11 on serum biochemical indicators of mice. (A) UA. (B) BUN. (C) CRE. (D) XOD. UA, uric acid; BUN, blood urea nitrogen; CRE, creatinine; XOD, xanthine oxidase. The same number of asterisks indicates no significant difference and the different number of asterisks indicates significant difference. (P < 0.05).
Figure 4
Figure 4
Effects of Lactobacillus paracasei X11 on proinflammatory factors of mice. (A) Serum IL-1β. (B) Serum LPS. (C) Liver IL-1β. (D) Kidney IL-1β. (E) Liver TNF-α. (F) Kidney TNF-α. (G) Liver MDA. (H) Kidney MDA. LPS, lipopolysaccharide; MDA, malondialdehyde. The same number of asterisks indicates no significant difference and the different number of asterisks indicates significant difference. (P < 0.05).
Figure 5
Figure 5
Effects of Lactobacillus paracasei X11 on metabolism enzyme of mice. (A) Liver ADA. (B) Liver XOD. ADA, adenosine deaminase; XOD, xanthine oxidase. The same number of asterisks indicates no significant difference and the different number of asterisks indicates significant difference. (P < 0.05).
Figure 6
Figure 6
Effects of Lactobacillus paracasei X11 on transporter expression level of mice. The same number of asterisks indicates no significant difference and the different number of asterisks indicates significant difference. (P < 0.05).
Figure 7
Figure 7
Effects of Lactobacillus paracasei X11 on gut microbe of mice. (A) Results of the taxonomic annotation. (B) Venn diagram of ASV/OTU in the feces. (C) α-Diversity indexes calculated with QIIME2 according to ASV/OTU numbers of each group (p < 0.05). (D) β-Diversity evaluated using the weighted UniFrac-based PCoA. (E) Bar graphs showing the relative abundance of different bacteria at the phylum level. (F) Relative abundances of Bacteroidetes at the phylum level (p < 0.05). (G) Relative abundances of Firmicutes at the phylum level (p < 0.05). (H) Changes in the Bac/Firm ratio in the different groups (p < 0.05). (I) Bar graphs showing the relative abundance of different bacteria at the genus level. (J) Relative abundances of Lactobacillus at the genus level (p < 0.05). (K) Cladogram based on LEfSe analysis showing community composition of the gut microbiota in mice. (L) Linear discriminant analysis (LDA) effect size (LEfSe) method was used to investigate bacterial community at the phylum level. LDA score higher than 2 indicates a higher relative abundance in the corresponding group than in other groups. ASV, amplicon sequence variant; OTU, operational taxonomic unit; PCoA, principal coordinates analysis. The meaning of the asterisk symbol indicates significant difference. (P < 0.05).

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