Skip to main content
Log in

The anti-hyperuricemic and gut microbiota regulatory effects of a novel purine assimilatory strain, Lactiplantibacillus plantarum X7022

  • Original Contribution
  • Published:
European Journal of Nutrition Aims and scope Submit manuscript

A Correction to this article was published on 17 April 2024

This article has been updated

Abstract

Purpose

Probiotics have been reported to effectively alleviate hyperuricemia and regulate the gut microbiota. The aim of this work was to study the in vivo anti-hyperuricemic properties and the mechanism of a novel strain, Lactiplantibacillus plantarum X7022.

Methods

Purine content and mRNA expression of purine assimilation related enzymes were determined by HPLC and qPCR, respectively. Hyperuricemic mice were induced by potassium oxonate and hypoxanthine. Uric acid (UA), blood urea nitrogen, creatinine and renal inflammation were examined by kits. The expression of renal UA transporters was subjected to western blotting. Kidney tissues were sectioned for histological analysis. The fecal short-chain fatty acids (SCFAs) were determined by HPLC, and gut microbiota was investigated using the 16S rDNA metagenomic sequencing.

Results

L. plantarum X7022 possesses a complete purine assimilation pathway and can exhaust xanthine, guanine, and adenine by 82.1%, 33.1%, and 12.6%, respectively. The strain exhibited gastrointestinal viability as 44% at the dose of 109 CFU/mL in mice. After four-week administration of the strain, a significant decrease of 35.5% in the serum UA level in hyperuricemic mice was achieved. The diminished contents of fecal propionate and butyrate were dramatically boosted. The treatment also alleviated renal inflammation and restored renal damage. The above physiological changes may due to the inhibited xanthine oxidase (XO) activity, as well as the expressional regulation of UA transporters (GLUT9, URAT1 and OAT1) to the normal level. Notably, gut microbiota dysbiosis in hyperuricemic mice was improved with the inflammation and hyperuricemia related flora depressed, and SCFAs production related flora promoted.

Conclusion

The strain is a promising probiotic strain for ameliorating hyperuricemia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Data availability

The datasets generated for this study are available on request to the corresponding author.

Change history

References

  1. Gliozzi M, Malara N, Muscoli S, Mollace V (2016) The treatment of hyperuricemia. Int J Cardiol 213:23–27. https://doi.org/10.1016/j.ijcard.2015.08.087

    Article  PubMed  Google Scholar 

  2. Dehlin M, Jacobsson L, Roddy E (2020) Global epidemiology of gout: prevalence, incidence, treatment patterns and risk factors. Nat Rev Rheumatol 16(7):380–390. https://doi.org/10.1038/s41584-020-0441-1

    Article  PubMed  Google Scholar 

  3. Chen-Xu M, Yokose C, Rai SK, Pillinger MH, Choi HK (2019) Contemporary prevalence of gout and hyperuricemia in the United States and Decadal Trends: The National Health and Nutrition Examination Survey, 2007–2016. Arthritis Rheumatol 71(6):991–999. https://doi.org/10.1002/art.40807

    Article  PubMed  PubMed Central  Google Scholar 

  4. Li Y, Shen ZY, Zhu BW, Zhang H, Zhang XY, Ding XQ (2021) Demographic, regional and temporal trends of hyperuricemia epidemics in mainland China from 2000 to 2019: a systematic review and meta-analysis. Glob Health Action 14(1):1874652. https://doi.org/10.1080/16549716.2021.1874652

    Article  PubMed  PubMed Central  Google Scholar 

  5. Kanbay M, Jensen T, Solak Y, Le M, Roncal-Jimenez C, Rivard C, Lanaspa MA, Nakagawa T, Johnson RJ (2016) Uric acid in metabolic syndrome: From an innocent bystander to a central player. Eur J Intern Med 29:3–8. https://doi.org/10.1016/j.ejim.2015.11.026

    Article  CAS  PubMed  Google Scholar 

  6. Lima WG, Martins-Santos MES, Chaves VE (2015) Uric acid as a modulator of glucose and lipid metabolism. Biochimie 116:17–23. https://doi.org/10.1016/j.biochi.2015.06.025

    Article  CAS  PubMed  Google Scholar 

  7. Hung SI, Chung WH, Liou LB, Chu CC, Lin M, Huang HP, Lin YL, Lan JL, Yang LC, Hong HS, Chen MJ, Lai PC, Wu MS, Chu CY, Wang KH, Chen CH, Fann CSJ, Wu JY, Chen YT (2005) HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. P Natl Acad Sci USA 102(17):4134–4139. https://doi.org/10.1073/pnas.0502360102

    Article  CAS  Google Scholar 

  8. Pascart T, Richette P (2018) Investigational drugs for hyperuricemia, an update on recent developments. Expert Opin Inv Drug 27(5):437–444. https://doi.org/10.1080/13543784.2018.1471133

    Article  CAS  Google Scholar 

  9. Cremonl C, Barbaro MR, Ventura M, Barbara G (2018) Pre- and probiotic overview. Curr Opin Pharmacol 43:87–92. https://doi.org/10.1016/j.coph.2018.08.010

    Article  CAS  Google Scholar 

  10. Wang R, Lin F, Ye C, Aihemaitijiang S, Halimulati M, Huang X, Jiang Z, Li L, Zhang Z (2023) Multi-omics analysis reveals therapeutic effects of Bacillus subtilis-fermented Astragalus membranaceus in hyperuricemia via modulation of gut microbiota. Food Chem 399:133993. https://doi.org/10.1016/j.foodchem.2022.133993

    Article  CAS  PubMed  Google Scholar 

  11. Hsieh CY, Lin HJ, Chen CH, Lai ECC, Yang YHK (2014) Chronic kidney disease and stroke. Lancet Neurol 13(11):1071. https://doi.org/10.1016/S1474-4422(14)70199-1

    Article  PubMed  Google Scholar 

  12. Wang J, Chen Y, Zhong H, Chen F, Regenstein J, Hu XS, Cai LY, Feng FQ (2022) The gut microbiota as a target to control hyperuricemia pathogenesis: Potential mechanisms and therapeutic strategies. Crit Rev Food Sci Nutr 62(14):3979–3989. https://doi.org/10.1080/10408398.2021.1874287

    Article  CAS  PubMed  Google Scholar 

  13. Li M, Yang DB, Mei L, Yuan L, Xie A, Yuan JL (2014) Screening and characterization of purine nucleoside degrading lactic acid bacteria isolated from Chinese sauerkraut and evaluation of the serum uric acid lowering effect in hyperuricemic rats. PLoS ONE 9(9):e105577. https://doi.org/10.1371/journal.pone.0105577

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Liu G, Liu YF, Ro KS, Du L, Tang YJ, Zhao L, Xie JL, Wei DZ (2022) Genomic characteristics of a novel strain Lactiplantibacillus plantarum X7021 isolated from the brine of stinky tofu for the application in food fermentation. Lwt-Food Sci Technol 156:113054. https://doi.org/10.1016/j.lwt.2021.113054

    Article  CAS  Google Scholar 

  15. Kuo YW, Hsieh SH, Chen JF, Liu CR, Chen CW, Huang YF, Ho HH (2021) Lactobacillus reuteri TSR332 and Lactobacillus fermentum TSF331 stabilize serum uric acid levels and prevent hyperuricemia in rats. PeerJ 9:e11209. https://doi.org/10.7717/peerj.11209

    Article  PubMed  PubMed Central  Google Scholar 

  16. Wang HN, Mei L, Deng Y, Liu YH, Wei XQ, Liu M, Zhou JR, Ma H, Zheng PY, Yuan JL, Li M (2019) Lactobacillus brevis DM9218 ameliorates fructose-induced hyperuricemia through inosine degradation and manipulation of intestinal dysbiosis. Nutrition 62:63–73. https://doi.org/10.1016/j.nut.2018.11.018

    Article  CAS  PubMed  Google Scholar 

  17. Yamanaka H, Taniguchi A, Tsuboi H, Kano H, Asami Y (2019) Hypouricaemic effects of yoghurt containing Lactobacillus gasseri PA-3 in patients with hyperuricaemia and/or gout: a randomised, double-blind, placebo-controlled study. Mod Rheumatol 29(1):146–150. https://doi.org/10.1080/14397595.2018.1442183

    Article  CAS  PubMed  Google Scholar 

  18. Chien CY, Chien YJ, Lin YH, Lin YH, Chan ST, Hu WC, Wu HF, Chiang CF, Hsu CL (2022) Supplementation of Lactobacillus plantarum (TCI227) prevented potassium-oxonate-induced hyperuricemia in rats. Nutrients 14(22):4832. https://doi.org/10.3390/nu14224832

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Vandenbussche F, Lefebvre DJ, De Leeuw U, Van Borm S, De Clercq K (2017) Laboratory validation of two real-time RT-PCR methods with 5 ’-tailed primers for an enhanced detection of foot-and-mouth disease virus. J Virol Methods 246:90–94. https://doi.org/10.1016/j.jviromet.2017.04.014

    Article  CAS  PubMed  Google Scholar 

  20. Wang XY, Sun GQ, Feng T, Zhang J, Huang X, Wang T, Xie ZQ, Chu XK, Yang J, Wang H, Chang SS, Gong YX, Ruan LF, Zhang GQ, Yan SY, Lian W, Du C, Yang DB, Zhang QL, Lin FF, Liu J, Zhang HY, Ge CR, Xiao SF, Ding J, Geng MY (2019) Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer’s disease progression. Cell Res 29(10):787–803. https://doi.org/10.1038/s41422-019-0216-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Xie DW, Shen YL, Su EZ, Du L, Xie JL, Wei DZ (2023) Anti-hyperuricemic, nephroprotective, and gut microbiota regulative effects of separated hydrolysate of alpha-Lactalbumin on potassium oxonate- and hypoxanthine-induced hyperuricemic mice. Mol Nutr Food Res 67(1):2200162. https://doi.org/10.1002/mnfr.202200162

    Article  CAS  Google Scholar 

  22. Jiang CT, Liu YF, Wang YJ, Su EZ, Du L, Tang YJ, Xie JL, Wei DZ (2022) Hypolipidemic effects of the fermented soymilk with a novel Lactiplantibacillus plantarum strain X7021 on mice via modulating lipid metabolism and gut microbiota. Int J Food Sci Technol 57(7):4555–4565. https://doi.org/10.1111/ijfs.15793

    Article  CAS  Google Scholar 

  23. Hsu CL, Hou YH, Wang CS, Lin SW, Jhou BY, Chen CC, Chen YL (2019) Antiobesity and Uric Acid-Lowering Effect of Lactobacillus plantarum GKM3 in High-Fat-Diet-Induced Obese Rats. J Am Coll Nutr 38(7):623–632. https://doi.org/10.1080/07315724.2019.1571454

    Article  CAS  PubMed  Google Scholar 

  24. Ni CX, Li X, Wang LL, Li X, Zhao JX, Zhang H, Wang G, Chen W (2021) Lactic acid bacteria strains relieve hyperuricaemia by suppressing xanthine oxidase activity via a short-chain fatty acid-dependent mechanism. Food Funct 12(15):7054–7067. https://doi.org/10.1039/d1fo00198a

    Article  CAS  PubMed  Google Scholar 

  25. Cao T, Li XY, Mao T, Liu H, Zhao QX, Ding XL, Li CG, Zhang LJ, Tian ZB (2017) Probiotic therapy alleviates hyperuricemia in C57BL/6 mouse model. Biomed Res-India 28(5):2244–2249

    CAS  Google Scholar 

  26. Yang B, Zheng FL, Stanton C, Ross RP, Zhao JX, Zhang H, Chen W (2021) Lactobacillus reuteri FYNLJ109L1 attenuating metabolic syndrome in mice via gut microbiota modulation and alleviating inflammation. Foods 10(9):2081. https://doi.org/10.3390/foods10092081

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Liu NX, Wang Y, Yang MF, Bian WX, Zeng L, Yin SG, Xiong ZQ, Hu Y, Wang SY, Meng BL, Sun J, Yang XW (2019) New rice-derived short peptide potently alleviated hyperuricemia induced by potassium oxonate in rats. J Agric Food Chem 67(1):220–228. https://doi.org/10.1021/acs.jafc.8b05879

    Article  CAS  PubMed  Google Scholar 

  28. Zhao J, Huang L, Sun CY, Zhao DS, Tang HJ (2020) Studies on the structure-activity relationship and interaction mechanism of flavonoids and xanthine oxidase through enzyme kinetics, spectroscopy methods and molecular simulations. Food Chem 323:126807. https://doi.org/10.1016/j.foodchem.2020.126807

    Article  CAS  PubMed  Google Scholar 

  29. Wu Y, Ye Z, Feng PY, Li R, Chen X, Tian XZ, Han R, Kakade A, Liu P, Li XK (2021) Limosilactobacillus fermentum JL-3 isolated from “Jiangshui” ameliorates hyperuricemia by degrading uric acid. Gut Microbes 13(1):1–18. https://doi.org/10.1080/19490976.2021.1897211

    Article  CAS  PubMed  Google Scholar 

  30. El Din UAAS, Salem MM, Abdulazim DO (2017) Uric acid in the pathogenesis of metabolic, renal, and cardiovascular diseases: a review. J Adv Res 8(5):537–548. https://doi.org/10.1016/j.jare.2016.11.004

    Article  CAS  Google Scholar 

  31. Mandal AK, Mount DB (2015) The molecular physiology of uric acid homeostasis. Annu Rev Physiol 77:323–345. https://doi.org/10.1146/annurev-physiol-021113-170343

    Article  CAS  PubMed  Google Scholar 

  32. Wang Z, Cui T, Ci XY, Zhao F, Sun YH, Li YZ, Liu R, Wu WD, Yi XL, Liu CX (2019) The effect of polymorphism of uric acid transporters on uric acid transport. J Nephrol 32(2):177–187. https://doi.org/10.1007/s40620-018-0546-7

    Article  PubMed  Google Scholar 

  33. Vavra J, Mancikova A, Pavelcova K, Hasikova L, Bohata J, Stiburkova B (2022) Functional characterization of rare variants in OAT1/SLC22A6 and OAT3/SLC22A8 urate transporters identified in a gout and hyperuricemia cohort. Cells-Basel 11(7):1063. https://doi.org/10.3390/cells11071063

    Article  CAS  Google Scholar 

  34. Zhao HY, Lu ZX, Lu YJ (2022) The potential of probiotics in the amelioration of hyperuricemia. Food Funct 13(5):2394–2414. https://doi.org/10.1039/d1fo03206b

    Article  CAS  PubMed  Google Scholar 

  35. Shao TJ, Shao L, Li HC, Xie ZJ, He ZX, Wen CP (2017) Combined signature of the fecal microbiome and metabolome in patients with gout. Front Microbiol 8:268. https://doi.org/10.3389/fmicb.2017.00268

    Article  PubMed  PubMed Central  Google Scholar 

  36. Usman TO, Areola ED, Badmus OO, Kim I, Olatunji LA (2018) Sodium acetate and androgen receptor blockade improve gestational androgen excess-induced deteriorated glucose homeostasis and antioxidant defenses in rats: roles of adenosine deaminase and xanthine oxidase activities. J Nutr Biochem 62:65–75. https://doi.org/10.1016/j.jnutbio.2018.08.018

    Article  CAS  PubMed  Google Scholar 

  37. Hamer HM, Jonkers DMAE, Bast A, Vanhoutvin SALW, Fischer MAJG, Kodde A, Troost FJ, Venema K, Brummer RJM (2009) Butyrate modulates oxidative stress in the colonic mucosa of healthy humans. Clin Nutr 28(1):88–93. https://doi.org/10.1016/j.clnu.2008.11.002

    Article  CAS  PubMed  Google Scholar 

  38. James A, Ke HM, Yao T, Wang YS (2023) The role of probiotics in purine metabolism, hyperuricemia and gout mechanisms and interventions. Food Rev Int 39(1):261–277. https://doi.org/10.1080/87559129.2021.1904412

    Article  Google Scholar 

  39. Smith PM, Howitt MR, Panikov N, Michaud M, Gallini CA, Bohlooly-Y M, Glickman JN, Garrett WS (2013) The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341(6145):569–573. https://doi.org/10.1126/science.1241165

    Article  CAS  PubMed  Google Scholar 

  40. Yao J, Chen Y, Xu M (2022) The critical role of short-chain fatty acids in health and disease: A subtle focus on cardiovascular disease-NLRP3 inflammasome-angiogenesis axis. Clin Immunol 238:109013. https://doi.org/10.1016/j.clim.2022.109013

    Article  CAS  PubMed  Google Scholar 

  41. Chu YL, Sun SL, Huang YF, Gao Q, Xie XF, Wang P, Li JX, Liang LF, He XH, Jiang YQ, Wang MJ, Yang JH, Chen XM, Zhou C, Zhao Y, Ding F, Zhang Y, Wu XD, Bai XY, Wu JQ, Wei X, Chen XH, Yue Z, Fang XD, Huang QC, Wang Z, Huang RY (2021) Metagenomic analysis revealed the potential role of gut microbiome in gout. Npj Biofilms Microbi 7(1):66. https://doi.org/10.1038/s41522-021-00235-2

    Article  CAS  Google Scholar 

  42. Yang XY, Zheng MX, Zhou ML, Zhou LM, Ge X, Pang N, Li HC, Li XY, Li MD, Zhang J, Huang XF, Zheng KY, Yu YH (2022) Lentinan supplementation protects the gut-liver axis and prevents steatohepatitis: The role of gut microbiota involved. Front Nutr 8:803691. https://doi.org/10.3389/fnut.2021.803691

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Binda C, Lopetuso LR, Rizzatti G, Gibiino G, Cennamo V, Gasbarrini A (2018) Actinobacteria: a relevant minority for the maintenance of gut homeostasis. Dig Liver Dis 50(5):421–428. https://doi.org/10.1016/j.dld.2018.02.012

    Article  PubMed  Google Scholar 

  44. Fukuda S, Toh H, Taylor TD, Ohno H, Hattori M (2012) Acetate-producing bifidobacteria protect the host from enteropathogenic infection via carbohydrate transporters. Gut Microbes 3(5):449–454

    Article  PubMed  Google Scholar 

  45. Jin G, Tang Q, Ma JH, Liu X, Zhou BQ, Sun Y, Pang XQ, Guo ZX, Xie RX, Liu TY, Wang BM, Cao HL (2021) Maternal emulsifier P80 intake induces gut dysbiosis in offspring and increases their susceptibility to colitis in adulthood. Msystems 6(2):e01337-e11320. https://doi.org/10.1128/mSystems.01337-20

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Amatjan M, Li N, He PK, Zhang BH, Mai XY, Jiang QL, Xie HC, Shao XN (2023) A novel approach based on gut microbiota analysis and network pharmacology to explain the mechanisms of action of Cichorium intybus L. formula in the improvement of hyperuricemic nephropathy in rats. Drug Des Dev Ther 17:107–128. https://doi.org/10.2147/Dddt.S389811

    Article  CAS  Google Scholar 

  47. Wan HT, Han JJ, Tang SS, Bao W, Lu CY, Zhou J, Ming TH, Li Y, Su XR (2020) Comparisons of protective effects between two sea cucumber hydrolysates against diet induced hyperuricemia and renal inflammation in mice. Food Funct 11(1):1074–1086. https://doi.org/10.1039/c9fo02425e

    Article  CAS  PubMed  Google Scholar 

  48. Li J, Sung CYJ, Lee N, Ni YQ, Pihlajamaki J, Panagiotou G, El-Nezami H (2016) Probiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice. Proc Natl Acad Sci U S A 113(9):E1306–E1315. https://doi.org/10.1073/pnas.1518189113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Parker BJ, Wearsch PA, Veloo ACM, Rodriguez-Palacios A (2020) The genus Alistipes: Gut bacteria with emerging implications to inflammation, cancer, and mental health. Front Immunol 11:906. https://doi.org/10.3389/fimmu.2020.00906

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Kaur H, Das C, Mande SS (2017) In silico analysis of putrefaction pathways in bacteria and its implication in colorectal cancer. Front Microbiol 8:2166. https://doi.org/10.3389/fmicb.2017.02166

    Article  PubMed  PubMed Central  Google Scholar 

  51. Wang BT, Kong QM, Li X, Zhao JX, Zhang H, Chen W, Wang G (2020) A high-fat diet increases gut microbiota biodiversity and energy expenditure due to nutrient difference. Nutrients 12(10):3197. https://doi.org/10.3390/nu12103197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Wanchai K, Yasom S, Tunapong W, Chunchai T, Eaimworawuthikul S, Thiennimitr P, Chaiyasut C, Pongchaidecha A, Chatsudthipong V, Chattipakorn S, Chattipakorn N, Lungkaphin A (2018) Probiotic Lactobacillus paracasei HII01 protects rats against obese-insulin resistance-induced kidney injury and impaired renal organic anion transporter 3 function. Clin Sci 132(14):1545–1563. https://doi.org/10.1042/CS20180148

    Article  CAS  Google Scholar 

  53. Gupta RS, Chen WJ, Adeolu M, Chai YJ (2013) Molecular signatures for the class Coriobacteriia and its different clades; proposal for division of the class Coriobacteriia into the emended order Coriobacteriales, containing the emended family Coriobacteriaceae and Atopobiaceae fam. nov., and Eggerthellales ord. nov., containing the family Eggerthellaceae fam. nov. Int J Syst Evol Microbiol 63:3379–3397. https://doi.org/10.1099/ijs.0.048371-0

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by National Key Research and Development Program of China (No. 2021YFC2100300; No. 2020YFA0907800), China; Natural Science Foundation of Shanghai (No. 21ZR1416200), China.

Author information

Authors and Affiliations

Authors

Contributions

ZY and ZL analyzed main data and wrote the main manuscript text; JCT and YDY prepared figures and tables; RKS and ZDH helped with the methodology; DL and XJL reviewed and edited manuscript text. All authors reviewed the manuscript.

Corresponding author

Correspondence to Lei Du.

Additional information

The original online version of this article was revised: Correct article note “Yuan Zou and Kum-Song Ro contributed equally to the work” has been updated.

Supplementary Information

Below is the link to the electronic supplementary material.

394_2023_3291_MOESM1_ESM.docx

Supplementary file1 (DOCX 22 KB) The primers used for real-time quantitative polymerase chain reaction (RT-qPCR) are shown in Table S1.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zou, Y., Ro, KS., Jiang, C. et al. The anti-hyperuricemic and gut microbiota regulatory effects of a novel purine assimilatory strain, Lactiplantibacillus plantarum X7022. Eur J Nutr 63, 697–711 (2024). https://doi.org/10.1007/s00394-023-03291-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00394-023-03291-w

Keywords

Navigation