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Uric acid extrarenal excretion: the gut microbiome as an evident yet understated factor in gout development

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Abstract

Humans do not produce uricase, an enzyme responsible for degrading uric acid. However, some bacteria residing in the gut can degrade one-third of the dietary and endogenous uric acid generated daily. New insights based on metagenomic and metabolomic approaches provide a new interest in exploring the involvement of gut microbiota in gout. Nevertheless, the exact mechanisms underlying this association are complex and have not been widely discussed. In this study, we aimed to review the evidence that suggests uric acid extrarenal excretion and gut microbiome are potential risk factors for developing gout. A literature search was performed in PubMed, Web of Science, and Google Scholar using several keywords, including “gut microbiome AND gout”. A remarkable intestinal dysbiosis and shifts in abundance of certain bacterial taxa in gout patients have been consistently reported among different studies. Under this condition, bacteria might have developed adaptive mechanisms for de novo biosynthesis and salvage of purines, and thus, a concomitant alteration in uric acid metabolism. Moreover, gut microbiota can produce substrates that might cross the portal vein so the liver can generate de novo purinogenic amino acids, as well as uric acid. Therefore, the extrarenal excretion of uric acid needs to be considered as a factor in gout development. Nevertheless, further studies are needed to fully understand the role of gut microbiome in uric acid production and its extrarenal excretion, and to point out possible bacteria or bacterial enzymes that could be used as probiotic coadjutant treatment in gout patients.

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References

  1. Ichida K, Matsuo H, Takada T et al (2012) Decreased extra-renal urate excretion is a common cause of hyperuricemia. Nat Commun 3:764. https://doi.org/10.1038/ncomms1756

    Article  CAS  PubMed  Google Scholar 

  2. Pasut G, Sergi M, Veronese FM (2008) Anti-cancer PEG-enzymes: 30 years old, but still a current approach. Adv Drug Deliv Rev 60:69–78. https://doi.org/10.1016/j.addr.2007.04.018

    Article  CAS  PubMed  Google Scholar 

  3. Casartelli A, Melino VJ, Baumann U et al (2019) Opposite fates of the purine metabolite allantoin under water and nitrogen limitations in bread wheat. Plant Mol Biol 99:477–497. https://doi.org/10.1007/s11103-019-00831-z

    Article  CAS  PubMed  Google Scholar 

  4. Szczurek P, Mosiichuk N, Woliński J et al (2017) Oral uricase eliminates blood uric acid in the hyperuricemic pig model. PLoS ONE 12:e0179195. https://doi.org/10.1371/journal.pone.0179195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Alvarez-Lario B, Macarron-Vicente J (2010) Uric acid and evolution. Rheumatology 49:2010–2015

    Article  CAS  PubMed  Google Scholar 

  6. Ramazzina I, Costa R, Cendron L et al (2010) An aminotransferase branch point connects purine catabolism to amino acid recycling. Nat Chem Biol 6:801–806. https://doi.org/10.1038/nchembio.445

    Article  CAS  PubMed  Google Scholar 

  7. Guo Z, Zhang J, Wang Z et al (2016) Intestinal microbiota distinguish gout patients from healthy humans. Sci Rep 6:20602. https://doi.org/10.1038/srep20602

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. O’Hara AM, Shanahan F (2006) The gut flora as a forgotten organ. EMBO Rep 7:688–693. https://doi.org/10.1038/sj.embor.7400731

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Papakostas K, Frillingos S (2012) Substrate selectivity of YgfU, a uric acid transporter from Escherichia coli. J Biol Chem 287:15684–15695. https://doi.org/10.1074/jbc.M112.355818

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Desai J, Steiger S, Anders HJ (2017) Molecular pathophysiology of gout. Trends Mol Med 23:756–768. https://doi.org/10.1016/j.molmed.2017.06.005

    Article  CAS  PubMed  Google Scholar 

  11. Dalbeth N, Gosling AL, Gaffo A, Abhishek A (2021) Gout. Lancet 397:1843–1855. https://doi.org/10.1016/S0140-6736(21)00569-9

    Article  CAS  PubMed  Google Scholar 

  12. Smith E, Hoy D, Cross M et al (2014) The global burden of gout: estimates from the Global Burden of Disease 2010 study. Ann Rheum Dis 73:1470–1476. https://doi.org/10.1136/annrheumdis-2013-204647

    Article  PubMed  Google Scholar 

  13. Ragab G, Elshahaly M, Bardin T (2017) Gout: an old disease in new perspective—A review. J Adv Res 8:495–511. https://doi.org/10.1016/j.jare.2017.04.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kuo C-F, Grainge MJ, Zhang W, Doherty M (2015) Global epidemiology of gout: prevalence, incidence, and risk factors. Nat Rev Rheumatol 11:649–662. https://doi.org/10.1038/nrrheum.2015.91

    Article  PubMed  Google Scholar 

  15. Vázquez-Mellado J, Cruz J, Guzmán S et al (2006) Severe tophaceous gout. Characterization of low socioeconomic level patients from México. Clin Exp Rheumatol 24:233–238

    PubMed  Google Scholar 

  16. Kim JW, Kwak SG, Lee H et al (2017) Prevalence and incidence of gout in Korea: data from the national health claims database 2007–2015. Rheumatol Int 37:1499–1506. https://doi.org/10.1007/s00296-017-3768-4

    Article  PubMed  Google Scholar 

  17. Krishnan E, Lessov-Schlaggar CN, Krasnow RE, Swan GE (2012) Nature versus nurture in Gout: a twin study. Am J Med 125:499–504. https://doi.org/10.1016/j.amjmed.2011.11.010

    Article  PubMed  Google Scholar 

  18. Misawa K, Hasegawa T, Mishima E et al (2020) Contribution of rare variants of the SLC22A12 gene to the missing heritability of serum urate levels. Genetics 214:1079–1090. https://doi.org/10.1534/GENETICS.119.303006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Smith EUR, Díaz-Torné C, Perez-Ruiz F, March LM (2010) Epidemiology of gout: an update. Best Pract Res Clin Rheumatol 24:811–827. https://doi.org/10.1016/j.berh.2010.10.004

    Article  CAS  PubMed  Google Scholar 

  20. Butler F, Alghubayshi A, Roman Y (2021) The epidemiology and genetics of hyperuricemia and gout across major racial groups: a literature review and population genetics secondary database analysis. J Pers Med 11:231. https://doi.org/10.3390/jpm11030231

    Article  PubMed  PubMed Central  Google Scholar 

  21. Beyl RN, Hughes L, Morgan S (2016) Update on importance of diet in gout. Am J Med 129:1153–1158. https://doi.org/10.1016/j.amjmed.2016.06.040

    Article  PubMed  Google Scholar 

  22. Kawamura Y, Nakaoka H, Nakayama A, Okada Y, Sakiyama M (2019) Genomewide association study revealed novel loci which aggravate asymptomatic hyperuricaemia into gout. Ann Rheum Dis 78:1430–1437

    Article  CAS  PubMed  Google Scholar 

  23. Li X, Song P, Li J et al (2015) Relationship between hyperuricemia and dietary risk factors in Chinese adults: a cross-sectional study. Rheumatol Int 35:2079–2089. https://doi.org/10.1007/s00296-015-3315-0

    Article  CAS  PubMed  Google Scholar 

  24. Sandoval-Plata G, Morgan K, Abhishek A (2021) Variants in urate transporters, ADH1B, GCKR and MEPE genes associate with transition from asymptomatic hyperuricaemia to gout: results of the first gout versus asymptomatic hyperuricaemia GWAS in Caucasians using data from the UK Biobank. Ann Rheum Dis 80:1220–1226. https://doi.org/10.1136/ANNRHEUMDIS-2020-219796

    Article  CAS  PubMed  Google Scholar 

  25. Maiuolo J, Oppedisano F, Gratteri S et al (2016) Regulation of uric acid metabolism and excretion. Int J Cardiol 213:8–14

    Article  PubMed  Google Scholar 

  26. Abooali M, Lall GS, Coughlan K et al (2014) Crucial involvement of xanthine oxidase in the intracellular signalling networks associated with human myeloid cell function. Sci Rep 4:6307. https://doi.org/10.1038/srep06307

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kang DH, Johnson RJ (2015) Uric acid metabolism and the kidney. In: Chronic Renal Disease. Academic Press, Cambridge, pp 418–428

    Book  Google Scholar 

  28. Benn CL, Dua P, Gurrell R et al (2018) Physiology of hyperuricemia and urate-lowering treatments. Front Med 5:160. https://doi.org/10.3389/fmed.2018.00160

    Article  Google Scholar 

  29. Kaneko K, Aoyagi Y, Fukuuchi T et al (2014) Total purine and purine base content of common foodstuffs for facilitating nutritional therapy for gout and hyperuricemia. Biol Pharm Bull 37:709–721. https://doi.org/10.1248/bpb.b13-00967

    Article  CAS  PubMed  Google Scholar 

  30. Choi HK, Atkinson K, Karlson EW et al (2004) Purine-rich foods, dairy and protein intake, and the risk of gout in men. N Engl J Med 350:1093–1103. https://doi.org/10.1056/nejmoa035700

    Article  CAS  PubMed  Google Scholar 

  31. Zhang Y, Woods R, Chaisson CE et al (2006) Alcohol consumption as a trigger of recurrent gout attacks. Am J Med 119:800.e13–8. https://doi.org/10.1016/j.amjmed.2006.01.020

    Article  CAS  Google Scholar 

  32. Towiwat P, Li ZG (2015) The association of vitamin C, alcohol, coffee, tea, milk and yogurt with uric acid and gout. Int J Rheum Dis 18:495–501. https://doi.org/10.1111/1756-185X.12622

    Article  CAS  PubMed  Google Scholar 

  33. Jamnik J, Rehman S, Blanco Mejia S et al (2016) Fructose intake and risk of gout and hyperuricemia: a systematic review and meta-analysis of prospective cohort studies. BMJ Open 6:e013191. https://doi.org/10.1136/bmjopen-2016-013191

    Article  PubMed  PubMed Central  Google Scholar 

  34. Ayoub-Charette S, Liu Q, Khan TA et al (2019) Important food sources of fructose-containing sugars and incident gout: A systematic review and meta-analysis of prospective cohort studies. BMJ Open 9:e024171. https://doi.org/10.1136/bmjopen-2018-024171

    Article  PubMed  PubMed Central  Google Scholar 

  35. Bobulescu IA, Moe OW (2012) Renal transport of uric acid: evolving concepts and uncertainties. Adv Chronic Kidney Dis 19:358–371

    Article  PubMed  PubMed Central  Google Scholar 

  36. So A, Thorens B (2010) Uric acid transport and disease. J Clin Invest 120:1791–1799. https://doi.org/10.1172/JCI42344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Matsuo H, Yamamoto K, Nakaoka H et al (2016) Genome-wide association study of clinically defined Gout identifies multiple risk loci and its association with clinical subtypes. Ann Rheum Dis 75:652–659. https://doi.org/10.1136/annrheumdis-2014-206191

    Article  CAS  PubMed  Google Scholar 

  38. Torres RJ, De Miguel E, Bailén R et al (2014) Tubular urate transporter gene polymorphisms differentiate patients with gout who have normal and decreased urinary uric acid excretion. J Rheumatol 41:1863–1870. https://doi.org/10.3899/jrheum.140126

    Article  CAS  PubMed  Google Scholar 

  39. Major TJ, Dalbeth N, Stahl EA, Merriman TR (2018) An update on the genetics of hyperuricaemia and gout. Nat Rev Rheumatol 14:351–353. https://doi.org/10.1038/s41584-018-0004-x

    Article  CAS  Google Scholar 

  40. Nakayama A, Nakaoka H, Yamamoto K et al (2017) GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes. Ann Rheum Dis 76:869–877. https://doi.org/10.1136/annrheumdis-2016-209632

    Article  CAS  PubMed  Google Scholar 

  41. Köttgen A, Albrecht E, Teumer A et al (2013) Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. Nat Genet 45:145–154. https://doi.org/10.1038/ng.2500

    Article  CAS  PubMed  Google Scholar 

  42. Son CN, Bang SY, Cho SK et al (2014) The frequency of single nucleotide polymorphisms and their association with uric acid concentration based on data from genome-wide association studies in the Korean population. Rheumatol Int 34:777–783. https://doi.org/10.1007/s00296-013-2939-1

    Article  CAS  PubMed  Google Scholar 

  43. Xu X, Li C, Zhou P, Jiang T (2016) Uric acid transporters hiding in the intestine. Pharm Biol 54:3151–3155

    Article  CAS  PubMed  Google Scholar 

  44. Takada T, Ichida K, Matsuo H et al (2014) ABCG2 dysfunction increases serum uric acid by decreased intestinal urate excretion. Nucleosides Nucleotides Nucleic Acids 33:275–281. https://doi.org/10.1080/15257770.2013.854902

    Article  CAS  PubMed  Google Scholar 

  45. Turnbaugh PJ, Ley RE, Hamady M et al (2007) The human microbiome project. Nature 449:804–810. https://doi.org/10.1038/nature06244

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Yang X, Xie L, Li Y, Wei C (2009) More than 9,000,000 unique genes in human gut bacterial community: estimating gene numbers inside a human body. PLoS ONE 4:e6074. https://doi.org/10.1371/journal.pone.0006074

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Kurokawa K, Itoh T, Kuwahara T et al (2007) Comparative metagenomics revealed commonly enriched gene sets in human gut microbiomes. DNA Res 14:169–181. https://doi.org/10.1093/dnares/dsm018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Tremaroli V, Bäckhed F (2012) Functional interactions between the gut microbiota and host metabolism. Nature 489:242–249

    Article  CAS  PubMed  Google Scholar 

  49. Canfora EE, Jocken JW, Blaak EE (2015) Short-chain fatty acids in control of body weight and insulin sensitivity. Nat Rev Endocrinol 11:577–591

    Article  CAS  PubMed  Google Scholar 

  50. Besten GD, Eunen KV, Groen A et al (2013) The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res 54:2325–2340

    Article  Google Scholar 

  51. Degnan PH, Taga ME, Goodman AL (2014) Vitamin B12 as a modulator of gut microbial ecology. Cell Metab 20:769–778

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Swanson DA, Liu ML, Baker PJ et al (2001) Targeted disruption of the methionine synthase gene in mice. Mol Cell Biol 21:1058–1065

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Takahashi-Iniguez T, Garcia-Hernandez E, Arreguin-Espinosa R et al (2012) Role of vitamin B12 on methylmalonyl-CoA mutase activity. J Zhejiang Univ 13:423–437

    Article  CAS  Google Scholar 

  54. Froese DS, Fowler B, Baumgartner MR (2019) Vitamin B12, folate, and the methionine remethylation cycle-biochemistry, pathways, and regulation. J Inherit Metab Dis 42:673–685

    Article  CAS  PubMed  Google Scholar 

  55. Mach N, Clark A (2017) Micronutrient deficiencies and the human gut microbiota. Trends Microbiol 25:607–610

    Article  CAS  PubMed  Google Scholar 

  56. Tehlivets O, Malanovic N, Visram M et al (2013) S-adenosyl-L-homocysteine hydrolase and methylation disorders: yeast as a model system. Biochim Biophys Acta 1832:204–215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Gill SR, Pop M, Deboy RT et al (2006) Metagenomic analysis of the human distal gut microbiome. Science 312:1355–1359

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Lin R, Liu W, Piao M, Zhu H (2017) A review of the relationship between the gut microbiota and amino acid metabolism. Amino Acids 49:2083–2090

    Article  CAS  PubMed  Google Scholar 

  59. Amorim Franco TM, Blanchard JS (2017) Bacterial branched-chain amino acid biosynthesis: structures, mechanisms, and drugability. Biochemistry 56:5849–5865. https://doi.org/10.1021/acs.biochem.7b00849

    Article  CAS  PubMed  Google Scholar 

  60. Price MN, Zane GM, Kuehl JV et al (2018) Filling gaps in bacterial amino acid biosynthesis pathways with high-throughput genetics. PLoS Genet 14:e1007147

    Article  PubMed  PubMed Central  Google Scholar 

  61. Smith NW, Shorten PR, Altermann E et al (2019) The classification and evolution of bacterial cross-feeding. Front Ecol Evol 7:153. https://doi.org/10.3389/fevo.2019.00153

    Article  Google Scholar 

  62. Sanchez-Pozo A, Gil A (2002) Nucleotides as semiessential nutritional components. Br J Nutr Suppl 1:S135–S137

    Article  Google Scholar 

  63. Uauy R, Quan R, Gil A (2002) Role of nucleotides in intestinal development and repair: implications for infant nutrition. J Nutr 124:1436S-1441S

    Article  Google Scholar 

  64. Singhal A, Macfarlane G, Macfarlane S et al (2008) Dietary nucleotides and fecal microbiota in formula-fed infants: a randomized controlled trial. Am J Clin Nutr 87:1785–1792

    Article  CAS  PubMed  Google Scholar 

  65. Sauer N, Mosenthin R, Bauer E (2011) The role of dietary nucleotides in single-stomached animals. Nutr Res Rev 24:46–59

    Article  CAS  PubMed  Google Scholar 

  66. Ronnestad I, Akiba Y, Kaji I, Kaunitz JD (2014) Duodenal luminal nutrient sensing. Curr Opin Pharmacol 19:67–75

    Article  PubMed  PubMed Central  Google Scholar 

  67. Alcedo KP, Bowser JL, Snider NT (2021) The elegant complexity of mammalian ecto-5′-nucleotidase (CD73). Trends Cell Biol S0962–8924(21):00100–00108. https://doi.org/10.1016/j.tcb.2021.05.008

    Article  CAS  Google Scholar 

  68. Crane JK, Shulgina I, Naeher TM (2007) Ecto-5’-nucleotidase and intestinal ion secretion by enteropathogenic Escherichia coli. Purinergic Signal 3:233–246

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Zimmermann H, Zebisch M, Sträter N (2012) Cellular function and molecular structure of ecto-nucleotidases. Purinergic Signal 8:437–502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Pastor-Anglada M, Urtasun N, Pérez-Torras S (2018) Intestinal nucleoside transporters: function, expression, and regulation. Compr Physiol 8:1003–1017

    Article  PubMed  Google Scholar 

  71. Rahman MF, Askwith C, Govindarajan R (2017) Molecular determinants of acidic pH-dependent transport of human equilibrative nucleoside transporter 3. J Biol Chem 292:14775–14785

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Boza JJ, Martínez-Augustin O (2002) Role and function of nucleotides in infant nutrition. Nestle Nutr Work Ser 47:165–184

    CAS  Google Scholar 

  73. Wang W, Wu Z, Lin G et al (2014) Glycine stimulates protein synthesis and inhibits oxidative stress in pig small intestinal epithelial cells. J Nutr 144:1540–1548

    Article  CAS  PubMed  Google Scholar 

  74. Beyoglu D, Idle JR (2012) The glycine deportation system and its pharmacological consequences. Pharmacol Ther 135:151–167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Kikuchi G, Motokawa Y, Yoshida T, Hiraga K (2008) Glycine cleavage system: reaction mechanism, physiological significance, and hyperglycinemia. Proc Jpn Acad Ser B Phys Biol Sci 84:246–263

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Bergen WG, Wu G (2009) Intestinal nitrogen recycling and utilization in health and disease. J Nutr 139:821–825

    Article  CAS  PubMed  Google Scholar 

  77. Chen Y, Dinges MM, Green A et al (2020) Absorptive transport of amino acids by the rat colon. Am J Physiol Gastrointest Liver Physiol 318:189–202. https://doi.org/10.1152/ajpgi.00277.2019.-The

    Article  Google Scholar 

  78. Howard A, Hirst BH (2011) The glycine transporter GLYT1 in human intestine: expression and function. Biol Pharm Bull 34:784–788

    Article  CAS  PubMed  Google Scholar 

  79. Richardson AJ, Mckain N, Wallace RJ (2013) Ammonia production by human faecal bacteria, and the enumeration, isolation and characterization of bacteria capable of growth on peptides and amino acids. BMC Microbiol 13:1–8

    Article  Google Scholar 

  80. Levitt DG, Levitt MD (2018) A model of blood-ammonia homeostasis based on a quantitative analysis of nitrogen metabolism in the multiple organs involved in the production, catabolism, and excretion of ammonia in humans. Clin Exp Gastroenterol 11:193–215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Handlogten ME, Hong S-P, Zhang L et al (2005) Expression of the ammonia transporter proteins Rh B glycoprotein and Rh C glycoprotein in the intestinal tract. Am J Physiol Gastrointest Liver Physiol 288:G1036–G1047

    Article  CAS  PubMed  Google Scholar 

  82. Blachier F, Boutry C, Bos C, Tomé D (2009) Metabolism and functions of L-glutamate in the epithelial cells of the small and large intestines. Am J Clin Nutr 90:814S-821S

    Article  CAS  PubMed  Google Scholar 

  83. Blachier F, Beaumont M, Andriamihaja M et al (2017) Changes in the luminal environment of the colonic epithelial cells and physiopathological consequences. Am J Pathol 187:476–486

    Article  CAS  PubMed  Google Scholar 

  84. Cory JG, Cory AH (2006) Critical roles of glutamine as nitrogen donors in purine and pyrimidine nucleotide synthesis: asparaginase treatment in childhood acute lymphoblastic leukemia. In Vivo 20:587–589

    CAS  PubMed  Google Scholar 

  85. Forchhammer K (2007) Glutamine signalling in bacteria. Front Biosci 12:358–370

    Article  CAS  PubMed  Google Scholar 

  86. Ludewig U, Neuhäuser B, Dynowski M (2007) Molecular mechanisms of ammonium transport and accumulation in plants. FEBS Lett 581:2301–2308

    Article  CAS  PubMed  Google Scholar 

  87. Bolton ET, Abelson PH, Aldous E (1952) Utilization of carbon dioxide in the synthesis of nucleic acid by escherichia coli. J Biol Chem 198:179–185

    Article  CAS  PubMed  Google Scholar 

  88. Xiong W, Lin PP, Magnusson L et al (2016) CO2-fixing one-carbon metabolism in a cellulose-degrading bacterium Clostridium thermocellum. Proc Natl Acad Sci USA 113:13180–13185. https://doi.org/10.1073/pnas.1605482113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Schultheisz HL, Szymczyna BR, Scott LG, Williamson JR (2008) Pathway engineered enzymatic de novo purine nucleotide synthesis. ACS Chem Biol 3:499–511. https://doi.org/10.1021/cb800066p

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Kilstrup M, Hammer K, Jensen PR, Martinussen J (2005) Nucleotide metabolism and its control in lactic acid bacteria. FEMS Microbiol Rev 29:555–590. https://doi.org/10.1016/j.femsre.2005.04.006

    Article  CAS  PubMed  Google Scholar 

  91. Ravanel S, Douce R, Rébeillé F (2011) Metabolism of folates in plants. Adv Bot Res 59:67–106 (Academic Press Inc)

    Article  Google Scholar 

  92. Sah S, Aluri S, Rex K, Varshney U (2015) One-carbon metabolic pathway rewiring in Escherichia coli reveals an evolutionary advantage of 10-formyltetrahydrofolate synthetase (Fhs) in survival under hypoxia. J Bacteriol 197:717–726

    Article  PubMed  PubMed Central  Google Scholar 

  93. Serganov A, Nudler E (2013) A decade of riboswitches. Cell 152:17–24

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Lim MY, Rho M, Song Y-M et al (2014) Stability of gut enterotypes in korean monozygotic twins and their association with biomarkers and diet. Sci Rep 4:7348. https://doi.org/10.1038/srep07348

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Shao T, juan, He Z xing, Xie Z jun, et al (2016) Characterization of ankylosing spondylitis and rheumatoid arthritis using 1H NMR-based metabolomics of human fecal extracts. Metabolomics 12:1–8. https://doi.org/10.1007/s11306-016-1000-2

    Article  CAS  Google Scholar 

  96. Méndez-Salazar EO, Vázquez-Mellado J, Casimiro-Soriguer CS et al (2021) Taxonomic variations in the gut microbiome of gout patients with and without tophi might have a functional impact on urate metabolism. Mol Med 27:50. https://doi.org/10.1186/s10020-021-00311-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Pan L, Han P, Ma S et al (2020) Abnormal metabolism of gut microbiota reveals the possible molecular mechanism of nephropathy induced by hyperuricemia. Acta Pharm Sin B 10:249–261

    Article  CAS  PubMed  Google Scholar 

  98. Chu Y, Sun S, Huang Y et al (2021) Metagenomic analysis revealed the potential role of gut microbiome in gout. NPJ Biofilms Microbiomes 7:66. https://doi.org/10.1038/s41522-021-00235-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We would like to thank the Consejo Nacional de Ciencia y Tecnología (CONACYT) for the grant FORDECYT-PRONACES/87754/2020. We also want to thank Yessica Zamudio-Cuevas, Karina Martínez-Flores, Javier Fernandez-Torres, Alberto López-Reyes, Berenice Palacios-González, and Carlos Martínez-Armenta for their valuable support. We thank Patricia Martínez-Nava for the manuscript proofreading.

Funding

This study was supported by the Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra”; and by the Consejo Nacional de Ciencia y Tecnología (CONACYT) grant FORDECYT-PRONACES/87754/2020.

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  1. Postgraduate Program in ICES, Facultad de Química, UNAM, Mexico City, Mexico

    Eder Orlando Méndez-Salazar

  2. Laboratorio de Líquido Sinovial, Instituto Nacional de Rehabilitación “Luis Guillermo Ibarra Ibarra”, Calzada México-Xochimilco 289, Arenal de Guadalupe, 14389, Mexico City, Mexico

    Gabriela Angélica Martínez-Nava

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EOMS: Made the conception of the work, the literature search, the analysis of data, draft the work, approved the final version of the manuscript and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. GAMN: Made substantial contribution to the design of the work, and in the interpretation of literature for the work. Revised critically the draft for important intellectual content, approved the final version of the manuscript and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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Correspondence to Gabriela Angélica Martínez-Nava.

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Méndez-Salazar, E.O., Martínez-Nava, G.A. Uric acid extrarenal excretion: the gut microbiome as an evident yet understated factor in gout development. Rheumatol Int 42, 403–412 (2022). https://doi.org/10.1007/s00296-021-05007-x

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  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-021-05007-x

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