肠道菌群在儿童高尿酸血症中的作用及微生态干预进展

陈雪纯; 周雪莲; 傅君芬

doi:10.11852/zgetbjzz2025-1016

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中国儿童保健杂志 ›› 2026, Vol. 34 ›› Issue (11) : 1263-1268. DOI: 10.11852/zgetbjzz2025-1016

综述

肠道菌群在儿童高尿酸血症中的作用及微生态干预进展

陈雪纯, 周雪莲, 傅君芬

作者信息 +

Role of the gut microbiota in pediatric hyperuricemia and advances in microbiota-targeted interventions

CHEN Xuechun, ZHOU Xuelian, FU Junfen

Author information +

文章历史 +

摘要

随着儿童青少年超重和肥胖率的持续上升,高尿酸血症在儿童中的发生率显著增加,但目前尚缺乏安全、有效且适用于儿童的治疗手段。近年来,研究提示肠道菌群可能成为调控尿酸代谢的重要靶点。然而,现有证据多来源于动物实验,其具体作用机制尚未完全阐明,临床转化仍面临菌株安全性、长期疗效及可行性等挑战。本文综述了肠道菌群在儿童高尿酸血症发生发展中的潜在机制,重点探讨其在调控嘌呤代谢、尿酸排泄与重吸收及炎症反应等环节中的作用,并总结了现有的微生态干预手段,同时阐述了其在临床应用中的前景与瓶颈,旨在为未来开发更安全、精准的儿童高尿酸血症干预策略提供理论依据与研究方向。

Abstract

With the rising prevalence of overweight and obesity among children and adolescents, the prevalence of hyperuricemia among children and adolescents has increased significantly. However, safe and effective treatments suitable for pediatric patients remain limited. Recent evidence suggests that the gut microbiota may be an important target for modulating uric acid metabolism. However, most available evidence comes from animal studies and the underlying mechanisms remain incompletely understood. Furthermore, clinical translation faces challenges related to strain safety, long-term efficacy, and practical feasibility. This review summarizes the potential mechanisms by which gut microbiota contribute to the development of pediatric hyperuricemia, with a focus on its roles in regulating purine metabolism, uric acid excretion and reabsorption, and inflammatory responses. In addition, existing microbiota-based interventions are reviewed, and their clinical prospects and limitations are discussed, aiming to provide a theoretical basis and research direction for developing safer and more precise therapeutic strategies for pediatric hyperuricemia.

导出引用

陈雪纯, 周雪莲, 傅君芬. 肠道菌群在儿童高尿酸血症中的作用及微生态干预进展[J]. 中国儿童保健杂志. 2026, 34(11): 1263-1268 https://doi.org/10.11852/zgetbjzz2025-1016

CHEN Xuechun, ZHOU Xuelian, FU Junfen. Role of the gut microbiota in pediatric hyperuricemia and advances in microbiota-targeted interventions[J]. Chinese Journal of Child Health Care. 2026, 34(11): 1263-1268 https://doi.org/10.11852/zgetbjzz2025-1016

中图分类号： R179

参考文献

[1] 中华医学会内分泌学分会.中国高尿酸血症与痛风诊疗指南(2019)[J].中华内分泌代谢杂志, 2020, 36(1):1-13.
Chinese Society of Endocrinology, Chinese Medical Association.Guideline for the diagnosis and management of hyperuricemia and gout in China(2019)[J].Chin J Endocrinol Metab, 2020, 36(1):1-13.(in Chinese)
[2] Rao J, Ye P, Lu J, et al.Prevalence and related factors of hyperuricaemia in Chinese children and adolescents: A pooled analysis of 11 population-based studies[J].Ann Med, 2022, 54(1):1608-1615.
[3] Zhou X, Lin X, Chen J, et al.Clinical spectrum transition and prediction model of nonalcoholic fatty liver disease in children with obesity[J].Front Endocrinol, 2022, 13:986841.
[4] Muntner P, Srinivasan S, Menke A, et al.Impact of childhood metabolic syndrome components on the risk of elevated uric acid in adulthood: The bogalusa heart study[J].Am J Med Sci, 2008, 335(5): 332-337.
[5] Su H, Liu T, Li Y, et al.Serum uric acid and its change with the risk of type 2 diabetes: A prospective study in China[J].Prim Care Diabetes, 2021, 15(6):1002-1006.
[6] Hsia SH, Chou IJ, Kuo CF, et al.Survival impact of serum uric acid levels in children and adolescents[J].Rheumatol Int, 2013, 33(11):2797-2802.
[7] Ye W, Zhou X, Xu Y, et al.Serum uric acid levels among Chinese children: Reference values and association with overweight/obesity[J].Clin Pediatr, 2024, 63(12): 1684-1690.
[8] Kubota M.Hyperuricemia in children and adolescents: Present knowledge and future directions[J].J Nutr Metab, 2019, 2019:3480718.
[9] Major TJ, Topless RK, Dalbeth N, et al.Evaluation of the diet wide contribution to serum urate levels: Meta-analysis of population based cohorts[J].BMJ, 2018, 363:k3951.
[10] Derrien M, Alvarez AS, de Vos WM.The gut microbiota in the first decade of life[J].Trends Microbiol, 2019, 27(12):997-1010.
[11] Packer M.Hyperuricemia and gout reduction by SGLT2 inhibitors in diabetes and heart failure: JACC review topic of the week[J].J Am Coll Cardiol, 2024, 83(2): 371-381.
[12] Yuan X, Chen R, Zhang Y, et al.Altered gut microbiota in children with hyperuricemia[J].Front Endocrinol, 2022, 13:848715.
[13] Li XM, Lv Q, Chen YJ, et al.Association between childhood obesity and gut microbiota: 16S rRNA gene sequencing-based cohort study[J].World J Gastroenterol, 2024, 30(16):2249-2257.
[14] Nakai K, Kadiiska MB, Jiang JJ, et al.Free radical production requires both inducible nitric oxide synthase and xanthine oxidase in LPS-treated skin[J].Proc Natl Acad Sci U S A, 2006, 103(12):4616-4621.
[15] Wei M, Hu Y, Zhang Z, et al.Lactiplantibacillus plantarum WLPL04 from human breast milk attenuates hyperuricemia via coordinated purine salvage pathway, renal transporter regulation, and gut microbiota remodeling[J].Nutrients, 2025, 17(21):3447.
[16] Zhong F, Feng X, Cao J, et al.Novel potential probiotics from Chinese Baijiu fermentation grains: Dual action of Lactiplantibacillus plantarum LTJ1/LTJ48 in uric acid reduction and gut microbiota restoration for hyperuricemia therapy in mice[J].Nutrients, 2025, 17(13): 2097.
[17] Wan H, Han J, Tang S, et al.Comparisons of protective effects between two sea cucumber hydrolysates against diet induced hyperuricemia and renal inflammation in mice[J].Food Funct, 2020, 11(1):1074-1086.
[18] Shi R, Ye J, Fan H, et al.Lactobacillus plantarum LLY-606 supplementation ameliorates hyperuricemia via modulating intestinal homeostasis and relieving inflammation[J].Food Funct, 2023, 14(12): 5663-5677.
[19] Cao J, Wang T, Liu Y, et al.Lactobacillus fermentum F40-4 ameliorates hyperuricemia by modulating the gut microbiota and alleviating inflammation in mice[J].Food Funct, 2023, 14(7): 3259-3268.
[20] Yamada N, Saito-Iwamoto C, Nakamura M, et al.Lactobacillus gasseri PA-3 uses the purines IMP, inosine and hypoxanthine and reduces their absorption in rats[J].Microorganisms, 2017, 5(1): 10.
[21] Li M, Wu X, Guo Z, et al.Lactiplantibacillus plantarum enables blood urate control in mice through degradation of nucleosides in gastrointestinal tract[J].Microbiome, 2023, 11(1): 153.
[22] El Ridi R, Tallima H.Physiological functions and pathogenic potential of uric acid: A review[J].J Adv Res, 2017, 8(5):487-493.
[23] Iswantini D, Nurhidayat N, Trivadila, et al.Activity and stability of uricase from Lactobacillus plantarum immobilizated on natural zeolite for uric acid biosensor[J].Pak J Biol Sci, 2014, 17(2): 277-281.
[24] Liu Y, Jarman JB, Low YS, et al.A widely distributed gene cluster compensates for uricase loss in hominids[J].Cell, 2023, 186(20): 4472-4473.
[25] Kasahara K, Kerby RL, Zhang Q, et al.Gut bacterial metabolism contributes to host global purine homeostasis[J].Cell Host Microbe, 2023, 31(6):1038-1053.e10.
[26] Matsuo H, Ichida K, Takada T, et al.Common dysfunctional variants in ABCG2 are a major cause of early-onset gout[J].Sci Rep, 2013, 3:2014.
[27] Zhang L, Liu J, Jin T, et al.Live and pasteurized Akkermansia muciniphila attenuate hyperuricemia in mice through modulating uric acid metabolism, inflammation, and gut microbiota[J].Food Funct, 2022, 13(23): 12412-12425.
[28] Li Y, Zhu J, Lin G, et al.Probiotic effects of Lacticaseibacillus rhamnosus 1155 and Limosilactobacillus fermentum 2644 on hyperuricemic rats[J].Front Nutr, 2022, 9: 993951.
[29] Ren L, Wang S, Liu S, et al.Postbiotic of Pediococcus acidilactici GQ01, a novel probiotic strain isolated from natural fermented wolfberry, attenuates hyperuricaemia in mice through modulating uric acid metabolism and gut microbiota[J].Foods, 2024, 13(6): 923.
[30] Özalp Kızılay D, Şen S, Ersoy B.Associations between serum uric acid concentrations and cardiometabolic risk and renal injury in obese and overweight children[J].J Clin Res Pediatr Endocrinol, 2019, 11(3):262-269.
[31] Zhou X, Ji S, Chen L, et al.Gut microbiota dysbiosis in hyperuricaemia promotes renal injury through the activation of NLRP3 inflammasome[J].Microbiome, 2024, 12(1):109.
[32] Guo Y, Yu Y, Li H, et al.Inulin supplementation ameliorates hyperuricemia and modulates gut microbiota in Uox-knockout mice[J].Eur J Nutr, 2021, 60(4): 2217-2230.
[33] Dalile B, Van Oudenhove L, Vervliet B, et al.The role of short-chain fatty acids in microbiota-gut-brain communication[J].Nat Rev Gastroenterol Hepatol, 2019, 16(8):461-478.
[34] Mo Q, Qin M, Liang H, et al.Lactiplantibacillus pentosus JWN01 and Lactiplantibacillus plantarum JWN02 attenuate renal fibrosis and pathological autophagy in hyperuricemic nephropathy via gut-kidney axis[J].Food Res Int, 2026, 228: 118376.
[35] Sun L, Ni C, Zhao J, et al.Probiotics, bioactive compounds and dietary patterns for the effective management of hyperuricemia: A review[J].Crit Rev Food Sci Nutr, 2024, 64(7):2016-2031.
[36] Liang L, Meng Z, Zhang F, et al.Lactobacillus gasseri LG08 and Leuconostoc mesenteroides LM58 exert preventive effect on the development of hyperuricemia by repairing antioxidant system and intestinal flora balance[J].Front Microbiol, 2023, 14: 1211831.
[37] Liu X, Han CH, Mao T, et al.Commensal Enterococcus faecalis W5 ameliorates hyperuricemia and maintains the epithelial barrier in a hyperuricemia mouse model[J].J Dig Dis, 2024, 25(1): 44-60.
[38] Hussain A, Rui B, Ullah H, et al.Limosilactobacillus reuteri HCS02-001 attenuates hyperuricemia through gut microbiota-dependent regulation of uric acid biosynthesis and excretion[J].Microorganisms, 2024, 12(4): 637.
[39] Li J, Song L, Liang X, et al.Lactobacillus plantarum TY-S8 ameliorates hyperuricemia through the regulation of gut microbiota and tryptophan metabolism in mice[J].Food Funct, 2026, 17(4): 1952-1969.
[40] Zhao H, Chen X, Zhang L, et al.Lacticaseibacillus rhamnosus Fmb14 prevents purine induced hyperuricemia and alleviate renal fibrosis through gut-kidney axis[J].Pharmacol Res, 2022, 182: 106350.
[41] Wang Z, Song L, Li X, et al.Lactiplantibacillus pentosus P2020 protects the hyperuricemia and renal inflammation in mice[J].Front Nutr, 2023, 10: 1094483.
[42] Wu J, Aga L, Tang L, et al.Lacticaseibacillus paracasei JS-3 isolated from "Jiangshui" ameliorates hyperuricemia by regulating gut microbiota and iTS metabolism[J].Foods, 2024, 13(9): 1371.
[43] Zhao S, Feng P, Hu X, et al.Probiotic Limosilactobacillus fermentum GR-3 ameliorates human hyperuricemia via degrading and promoting excretion of uric acid[J].iScience, 2022, 25(10): 105198.
[44] Cai JR, Chen XW, He YJ, et al.Washed microbiota transplantation reduces serum uric acid levels in patients with hyperuricaemia[J].World J Clin Cases, 2022, 10(11):3401-3413.
[45] Xie WR, Yang XY, Deng ZH, et al.Effects of washed microbiota transplantation on serum uric acid levels, symptoms, and intestinal barrier function in patients with acute and recurrent gout: A pilot study[J].Dig Dis Basel Switz, 2022, 40(5):684-690.
[46] Cai L, Li Q, Deng Y, et al.Construction and expression of recombinant uricase-expressing genetically engineered bacteria and its application in rat model of hyperuricemia[J].Int J Mol Med, 2020, 45(5):1488-1500.
[47] Zhao R, Li Z, Sun Y, et al.Engineered Escherichia coli Nissle 1917 with urate oxidase and an oxygen-recycling system for hyperuricemia treatment[J].Gut Microbes, 2022, 14(1): 2070391.
[48] Zou ZP, Li JL, Zhang YF, et al.Empowering probiotics with high xanthine transport for effective hyperuricemia management[J].Gut Microbes, 2024, 16(1): 2399213.
[49] Gencer G, Mancuso C, Chua KJ, et al.Engineering Escherichia coli for diagnosis and management of hyperuricemia[J].Front Bioeng Biotechnol, 2023, 11: 1191162.
[50] Stewart CJ, Ajami NJ, O′Brien JL, et al.Temporal development of the gut microbiome in early childhood from the TEDDY study[J].Nature, 2018, 562(7728):583-588.
[51] de Meij TGJ, Budding AE, de Groot EFJ, et al.Composition and stability of intestinal microbiota of healthy children within a Dutch population[J].FASEB J, 2016, 30(4): 1512-1522.
[52] Ronan V, Yeasin R, Claud EC.Childhood development and the microbiome-the intestinal microbiota in maintenance of health and development of disease during childhood development[J].Gastroenterology, 2021, 160(2):495-506.