This study aimed to explore the mechanism by which Limosilactobacillus reuteri FQ56 alleviates hyperuricemia in mice through comparative genomics analysis.A total of 24 male Kunming mice, aged 5 weeks, were selected for the study and were given daily intervention with L.reuteri at a dose of 109 CFU.For the final two weeks, hyperuricemia was induced by the uricase inhibitor potassium oxonate and hypoxanthine.At the end of the experiment, serum uric acid levels, xanthine oxidase (XOD) activity, kidney damage, and changes in gut microbiota and short-chain fatty acids (SCFAs) levels were assessed.Results showed that L.reuteri FQ56 significantly reduced serum uric acid levels in the mice, inhibited the activity of XOD in both the liver and serum, and alleviated kidney damage induced by hyperuricemia.Additionally, L.reuteri FQ56 increased the abundance of SCFA-producing bacteria, such as Roseburia and Eubacterium_xylanophilum, and raised SCFA concentrations in the feces of the mice.Comparative genomics analysis revealed that the FQ56 strain possesses a greater number of glycoside hydrolase genes, particularly from the GH1 family.These genes may help regulate gut microbiota composition and promote the hydrolysis of polysaccharides in the gut, thereby stimulating SCFA production in the colon and inhibiting XOD activity in both serum and liver, ultimately alleviating hyperuricemia.This study provides new insights into the mechanisms by which probiotics alleviate hyperuricemia, particularly the role of glycoside hydrolase genes in this process, offering a theoretical basis for future research and clinical applications.
[1] TIMSANS J, PALOMÄKI A, KAUPPI M.Gout and hyperuricemia:A narrative review of their comorbidities and clinical implications[J].Journal of Clinical Medicine, 2024, 13(24):7616.
[2] YAMANAKA H, TANIGUCHI A, TSUBOI H, et al.Hypouricaemic effects of yoghurt containing Lactobacillus gasseri PA-3 in patients with hyperuricaemia and/or gout:A randomised, double-blind, placebo-controlled study[J].Modern Rheumatology, 2019, 29(1):146-150.
[3] WANG H N, MEI L, DENG Y, et al.Lactobacillus brevis DM9218 ameliorates fructose-induced hyperuricemia through inosine degradation and manipulation of intestinal dysbiosis[J].Nutrition, 2019, 62:63-73.
[4] 金方, 杨虹.降血尿酸益生菌株的筛选和降血尿酸机理的探索[J].微生物学通报, 2018, 45(8):1757-1769.
JIN F, YANG H.Isolation of hypouricemic probiotics and exploration their effects on hyperuricemic rats[J].Microbiology China, 2018, 45(8):1757-1769.
[5] HSU C L, HOU Y H, WANG C S, et al.Antiobesity and uric acid-lowering effect of Lactobacillus plantarum GKM3 in high-fat-diet-induced obese rats[J].Journal of the American College of Nutrition, 2019, 38(7):623-632.
[6] ADEYANJU O A, BADEJOGBIN O C, AREOLA D E, et al.Sodium butyrate arrests pancreato-hepatic synchronous uric acid and lipid dysmetabolism in high fat diet fed Wistar rats[J].Biomedicine & Pharmacotherapy, 2021, 133:110994.
[7] GUO Z, ZHANG J C, WANG Z L, et al.Intestinal microbiota distinguish gout patients from healthy humans[J].Scientific Reports, 2016, 6:20602.
[8] WU Y, YE Z, FENG P Y, et al.Limosilactobacillus fermentum JL-3 isolated from “Jiangshui” ameliorates hyperuricemia by degrading uric acid[J].Gut Microbes, 2021, 13(1):1897211.
[9] NI C X, LI X, WANG L L, et al.Lactic acid bacteria strains relieve hyperuricaemia by suppressing xanthine oxidase activity via a short-chain fatty acid-dependent mechanism[J].Food & Function, 2021, 12(15):7054-7067.
[10] 朱广素, 王刚, 王园园, 等.三株植物乳杆菌对代谢综合征大鼠肠道菌群的影响[J].食品与发酵工业, 2018, 44(9):53-60.
ZHU G S, WANG G, WANG Y Y, et al.Effects of three Lactobacillus plantarum strains on gut microbiota in metabolic syndrome rats[J].Food and Fermentation Industries, 2018, 44(9):53-60.
[11] QIN Z Z, WANG S B, LIN Y H, et al.Antihyperuricemic effect of mangiferin aglycon derivative J99745 by inhibiting xanthine oxidase activity and urate transporter 1 expression in mice[J].Acta Pharmaceutica Sinica B, 2018, 8(2):306-315.
[12] 王琳琳. 双歧杆菌对便秘的影响及其作用机理研究 [D].无锡:江南大学, 2017.
WANG L L.Study of the effects and mechanisms of bifidobacteria on constipation alleviation [D].Wuxi:Jiangnan University, 2017.
[13] 林麟, 杜如冰, 吴群, 等.基于比较基因组学解析耐酸乳杆菌G10的多碳源利用特征[J].微生物学通报, 2022, 49(8):3279-3292.
LIN L, DU R B, WU Q, et al.Comparative genomics-based analysis of Lactobacillus acetotolerans G10, a strain using multiple carbon sources[J].Microbiology China, 2022, 49(8):3279-3292.
[14] ANAIZI N.The impact of uric acid on human health:Beyond gout and kidney stones[J].Ibnosina Journal of Medicine and Biomedical Sciences, 2023, 15(3):110-116.
[15] TANIGUCHI T, OMURA K, MOTOKI K, et al.Hypouricemic agents reduce indoxyl sulfate excretion by inhibiting the renal transporters OAT1/3 and ABCG2[J].Scientific Reports, 2021, 11:7232.
[16] KURAJOH M, FUKUMOTO S, EMOTO M, et al.Independent association of plasma xanthine oxidoreductase activity with serum uric acid level based on stable isotope-labeled xanthine and liquid chromatography/triple quadrupole mass spectrometry:MedCity21 health examination registry[J].Clinical Chemistry and Laboratory Medicine, 2020, 58(5):780-786.
[17] WANG J, CHEN Y, ZHONG H, et al.The gut microbiota as a target to control hyperuricemia pathogenesis:Potential mechanisms and therapeutic strategies[J].Critical Reviews in Food Science and Nutrition, 2022, 62(14):3979-3989.
[18] YIN H, LIU N, CHEN J.The role of the intestine in the development of hyperuricemia[J].Frontiers in Immunology, 2022, 13:845684.
[19] LIU H C, NIE C X, HU X Z, et al.Highland barley β-glucan supplementation attenuated hepatic lipid accumulation in Western diet-induced non-alcoholic fatty liver disease mice by modulating gut microbiota[J].Food & Function, 2024, 15(3):1250-1264.
[20] SCHWIERTZ A, LEHMANN U, JACOBASCH G, et al.Influence of resistant starch on the SCFA production and cell counts of butyrate-producing Eubacterium spp.in the human intestine[J].Journal of Applied Microbiology, 2002, 93(1):157-162.
[21] YU K H, SEE L C, HUANG Y C, et al.Dietary factors associated with hyperuricemia in adults[J].Seminars in Arthritis and Rheumatism, 2008, 37(4):243-250.
[22] 伍亚龙, 杨恺, 史梅莓, 等.全基因组测序揭示两株泡菜源植物乳杆菌基因型差异和潜在益生特性[J].微生物学报, 2023, 63(7):2880-2898.
WU Y L, YANG K, SHI M M, et al.Whole-genome sequencing reveals genotypic differences and potential probiotic properties of two Paocai-derived Lactiplantibacillus plantarum strains[J].Acta Microbiologica Sinica, 2023, 63(7):2880-2898.
[23] 郁惠蕾, 许建和, 林国强.糖苷水解酶在糖苷合成中的应用概况[J].有机化学, 2006, 26(8):1052-1058.
YU H L, XU J H, LIN G Q.Application of glycosidase to glycoside synthesis[J].Chinese Journal of Organic Chemistry, 2006, 26(8):1052-1058.
[24] 刘颖, 董盼盼, 孙丽芳, 等.嗜冷德沃斯氏菌来源GH1家族β-葡萄糖苷酶Bgl59的原核表达及酶学性质分析[J].微生物学报, 2024, 64 (8):2955-2966.
LIU Y, DONG P P, SUN L F, et al.Prokaryotic expression and characterization of the GH1 β-glucosidase Bgl59 from Devosia psychrophila[J].Acta Microbiologica Sinica, 2024, 64 (8):2955-2966.
[25] 孙红, 柴丽娟, 方冠宇, 等.窖泥中梭菌和互营球菌交互作用对生长和短链脂肪酸代谢的影响[J].食品与发酵工业, 2022, 48(15):24-32.
SUN H, CHAI L J, FANG G Y, et al.Effect of co-culture of Clostridium strains and Novisyntrophococcus fermenticellae, isolated from pit mud, on growth and short-chain fatty acid metabolism[J].Food and Fermentation Industries, 2022, 48(15):24-32.
