Fructose consumption has risen dramatically in recent decades due to the use of sucrose and high fructose corn syrup in beverages and processed foods, contributing to rising rates of hyperuricemia. The purpose of this experiment was to explore the anti-hyperuricemia effects of an active oligopeptide (GPSGRP) derived from sea cucumber in fructose induced hyperuricemia mouse model, and to clarify the underlying mechanism in sight of gut microbiota and serum metabolites. Peptide GPSGRP treatment rebalanced uric acid metabolism and alleviated inflammatory response in mice. In addition, treatment with GPSGRP decreased the abundance of Bacteroides and Proteobacteria at the phylum level, Muribaculum, Prevotella and Bacteroides at the genus level, and inhibited the related pathways of purine metabolism and glycolysis/gluconeogenesis metabolism. Moreover, serum metabolites, including linoleic acid, indole and its derivatives, arachidonic acid and uridine, as well as related metabolic pathways, such as tricarboxylic acid cycle, ketone production and sugar production, were altered in response to GPSGRP treatment. This study provides a valuable reference for the application and development of marine biological peptides in uric acid management.
S.M. Guo, Y.T. Liu, S.R. He, et al., Differential relationship of uric acid to mortality and clinical biomarkers of aging according to grip strength in older adults: a cohort study, Aging (Albany NY) 13 (2021) 10555-10583. https://doi.org/10.18632/aging.202820.
J.H. Siqueira, T.S.S. Pereira, G. Velasquez-Melendez, et al., Sugar-sweetened soft drinks consumption and risk of hyperuricemia: results of the ELSA-Brasil study, Nutr. Metab. Cardiovasc. Dis. 31 (2021) 2004-2013. https://doi.org/10.1016/j.numecd.2021.04.008.
A.F. Saad, J. Dickerson, T.B. Kechichian, et al., High-fructose diet in pregnancy leads to fetal programming of hypertension, insulin resistance, and obesity in adult offspring, Am. J. Obstet. Gynecol. 215(3) (2016) 378.e371-378.e376. https://doi.org/10.1016/j.ajog.2016.03.038.
T. Nakagawa, K.R. Tuttle, R.A. Short, et al., Hypothesis: fructose-induced hyperuricemia as a causal mechanism for the epidemic of the metabolic syndrome, Nat. Clin. Pract. Nephrol. 1 (2005) 80-86. https://doi.org/10.1038/ncpneph0019.
Y. Zhu, R.X. Zhang, Y. Wei, et al., Rice peptide and collagen peptide prevented potassium oxonate-induced hyperuricemia and renal damage, Food Biosci. 42 (2021) 101147. https://doi.org/10.1016/j.fbio.2021.101147.
F.E. García-Arroyo, G. Gonzaga-Sánchez, E. Tapia, et al., Osthol ameliorates kidney damage and metabolic syndrome induced by a high-fat/high-sugar diet, Int. J. Mol. Sci. 22 (2021) 2431. https://doi.org/10.3390/ijms22052431.
R.J. Johnson, G.L. Bakris, C. Borghi, et al., Hyperuricemia, acute and chronic kidney disease, hypertension, and cardiovascular disease: report of a scientific workshop organized by the national kidney foundation, Am. J. Kidney Dis. 71 (2018) 851-865. https://doi.org/10.1053/j.ajkd.2017.12.009.
G. Liu, X.F. Chen, X. Lu, et al., Sunflower head enzymatic hydrolysate relives hyperuricemia by inhibiting crucial proteins (xanthine oxidase, adenosine deaminase, uric acid transporter1) and restoring gut microbiota in mice, J. Funct. Foods 72 (2020) 104055. https://doi.org/10.1016/j.jff.2020.104055.
Y.R. Yu, Q.P. Liu, H.C. Li, et al., Alterations of the gut microbiome associated with the treatment of hyperuricaemia in male rats, Front. Microbiol. 9 (2018) 2233. https://doi.org/10.3389/fmicb.2018.02233.
S. Zhao, P.Y. Feng, X.G. Hu, et al., Probiotic Limosilactobacillus fermentum GR-3 ameliorates human hyperuricemia via degrading and promoting excretion of uric acid, iScience 25 (2022) 105198. https://doi.org/10.1016/j.isci.2022.105198.
C.Y. Lu, S.S. Tang, J.J. Han, et al., Apostichopus japonicus oligopeptide induced heterogeneity in the gastrointestinal tract microbiota and alleviated hyperuricemia in a microbiota-dependent manner, Mol. Nutr. Food Res. 65 (2021) 2100147. https://doi.org/10.1002/mnfr.202100147
Y.M. Huang, S.Q. Fan, G.D. Lu, et al., Systematic investigation of the amino acid profiles that are correlated with xanthine oxidase inhibitory activity: effects, mechanism and applications in protein source screening, Free Radical Biol. Med. 177 (2021) 326-336. https://doi.org/10.1016/j.freeradbiomed.2021.11.004.
T. Ishikawa, T. Takahashi, T. Taniguchi, et al., Dotinurad: a novel selective urate reabsorption inhibitor for the treatment of hyperuricemia and gout, Expert Opin. Pharmacother. 22 (2021) 1397-1406. https://doi.org/10.1080/14656566.2021.1918102.
N.T.P. Nong, J.L. Hsu, Characteristics of food protein-derived antidiabetic bioactive peptides: a literature update, Int. J. Mol. Sci. 22 (2021) 9508. https://doi.org/10.3390/ijms22179508.
P. Antony, R. Vijayan, Bioactive peptides as potential nutraceuticals for diabetes therapy: a comprehensive review, Int. J. Mol. Sci. 22 (2021) 9059. https://doi.org/10.3390/ijms22169059.
M. Muttenthaler, G.F. King, D.J. Adams, et al., Trends in peptide drug discovery, Nat. Rev. Drug Discovery 20 (2021) 309-325. https://doi.org/10.1038/s41573-020-00135-8.
S.P. Patil, A. Goswami, K. Kalia, et al., Plant-derived bioactive peptides: a treatment to cure diabetes, Int. J. Peptide Res. Therapeut. 26 (2020) 955-968. https://doi.org/10.1007/s10989-019-09899-z.
T.L. Wargasetia, H. Ratnawati, N. Widodo, et al., Bioinformatics study of sea cucumber peptides as antibreast cancer through inhibiting the activity of overexpressed protein (egfr, pi3k, akt1, and cdk4), Cancer Inform. 20 (2021) 11769351211031864. https://doi.org/10.1177/11769351211031864.
X.W. Xiang, X.L. Zhou, R. Wang, et al., Protective effect of tuna bioactive peptide on dextran sulfate sodium-induced colitis in mice, Mar. Drugs 19 (2021) 127. https://doi.org/10.3390/md19030127.
Z.F. Bhat, S. Kumar, H.F. Bhat, Bioactive peptides of animal origin: a review, J. Food Sci. Technol. 52 (2015) 5377-5392. https://doi.org/10.1007/s13197-015-1731-5.
H.T. Wan, J.J. Han, S.S. Tang, et al., Comparisons of protective effects between two sea cucumber hydrolysates against diet induced hyperuricemia and renal inflammation in mice, Food Funct. 11 (2020) 1074-1086. https://doi.org/10.1039/c9fo02425e.
A. Mehmood, L. Zhao, M. Ishaq, et al., Anti-hyperuricemic potential of stevia (Stevia rebaudiana Bertoni) residue extract in hyperuricemic mice, Food Funct. 11 (2020) 6387-6406. https://doi.org/10.1039/C9FO02246E.
J.X. Zhang, X. Lin, J. Xu, et al., Hyperuricemia inhibition protects sd rats against fructose-induced obesity hypertension via modulation of inflammation and renin-angiotensin system in adipose tissue, Exp. Clin. Endocrinol. Diabetes 129 (2021) 314-321. https://doi.org/10.1055/a-1023-6710.
J. Ye, C.H. Shen, Y.Y. Huang, et al., Anti-fatigue activity of sea cucumber peptides prepared from Stichopus japonicus in an endurance swimming rat model, J. Sci. Food Agric. 97 (2017) 4548-4556. https://doi.org/10.1002/jsfa.8322.
S. Reagan-Shaw, M. Nihal, N. Ahmad, Dose translation from animal to human studies revisited, FASEB J. 22 (2008) 659-661. https://doi.org/10.1096/fj.07-9574LSF.
L. Ding, L.Y. Zhang, H.H. Shi, et al., EPA-enriched ethanolamine plasmalogen alleviates atherosclerosis via mediating bile acids metabolism, J. Funct. Foods 66 (2020) 103824. https://doi.org/10.1016/j.jff.2020.103824.
J.J. Han, Z.Y. Wang, C.Y. Lu, et al., The gut microbiota mediates the protective effects of anserine supplementation on hyperuricaemia and associated renal inflammation, Food Funct. 12 (2021) 9030-9042. https://doi.org/10.1039/D1FO01884A.
Y. Pu, J. Pan, Y. Yao, et al., Ecotoxicological effects of erythromycin on a multispecies biofilm model, revealed by metagenomic and metabolomic approaches, Environ. Pollut. 276 (2021) 116737. https://doi.org/10.1016/j.envpol.2021.116737.
Y.L. Qiao, J.J. Zhou, J.H. Liang, et al., Uncaria rhynchophylla ameliorates unpredictable chronic mild stress-induced depression in mice via activating 5-HT1A receptor: insights from transcriptomics, Phytomedicine 81 (2021) 153436. https://doi.org/10.1016/j.phymed.2020.153436.
R.R. Zhou, D. He, J. Xie, et al., The synergistic effects of polysaccharides and ginsenosides from American ginseng (Panax quinquefolius L.) ameliorating cyclophosphamide-induced intestinal immune disorders and gut barrier dysfunctions based on microbiome-metabolomics analysis, Front. Immunol. 12 (2021) 665901. https://doi.org/10.3389/fimmu.2021.665901.
M. Kanehisa, Y. Sato, KEGG Mapper for inferring cellular functions from protein sequences, Protein Sci. 29 (2020) 28-35. https://doi.org/10.1002/pro.3711.
J. Joseph, R. Sara, M. Sonia Blanco, et al., Fructose intake and risk of gout and hyperuricemia: a systematic review and meta-analysis of prospective cohort studies, BMJ Open 6 (2016) e013191. https://doi.org/10.1136/bmjopen-2016-013191.
M.H. Do, E. Lee, M.J. Oh, et al., High-glucose or -fructose diet cause changes of the gut microbiota and metabolic disorders in mice without body weight change, Nutrients 10 (2018) 761. https://doi.org/10.3390/nu10060761.
N. Dalbeth, A. Phipps Green, M.E. House, et al., Body mass index modulates the relationship of sugar-sweetened beverage intake with serum urate concentrations and gout, Arthritis Res. Ther. 17 (2015) 263. https://doi.org/10.1186/s13075-015-0781-4.
M.A. Lanaspa, L.G. Sanchez-Lozada, Y.J. Choi, et al., Uric acid induces hepatic steatosis by generation of mitochondrial oxidative stress: potential role in fructose-dependent and -independent fatty liver, J. Biol. Chem. 287 (2012) 40732-40744. https://doi.org/10.1074/jbc.M112.399899.
M. Pavlicevic, E. Maestri, M. Marmiroli, Marine bioactive peptides: an overview of generation, structure and application with a focus on food sources, Mar. Drugs 18 (2020) 424. https://doi.org/10.3390/md18080424.
J.J. Han, X.F. Wang, S.S. Tang, et al., Protective effects of tuna meat oligopeptides (TMOP) supplementation on hyperuricemia and associated renal inflammation mediated by gut microbiota, FASEB J. 34 (2020) 5061-5076. https://doi.org/10.1096/fj.201902597RR.
W.L. Shen, T. Matsui, Current knowledge of intestinal absorption of bioactive peptides, Food Funct. 8 (2017) 4306-4314. https://doi.org/10.1039/C7FO01185G.
K.W. Ter Horst, M.J. Serlie, Fructose consumption, lipogenesis, and non-alcoholic fatty liver disease, Nutrients 9 (2017) 981. https://doi.org/10.3390/nu9090981.
Y. Zhou, L. Fang, L. Jiang, et al., Uric acid induces renal inflammation via activating tubular NF-κB signaling pathway, PLoS ONE 7 (2012) e39738. https://doi.org/10.1371/journal.pone.0039738.
J.Y. Tan, L.P. Wan, X.F. Chen, et al., Conjugated linoleic acid ameliorates high fructose-induced hyperuricemia and renal inflammation in rats via NLRP3 inflammasome and TLR4 signaling pathway, Mol. Nutr. Food Res. 63 (2019) 1801402. https://doi.org/10.1002/mnfr.201801402.
A.A. Shigeoka, J.L. Mueller, A. Kambo, et al., An inflammasome-independent role for epithelial-expressed Nlrp3 in renal ischemia-reperfusion injury, J. Immunol. 185 (2010) 6277-6285. https://doi.org/10.4049/jimmunol.1002330.
X.F. Qi, Y.F. Ma, K.F. Guan, et al., Whey protein peptide PEW attenuates hyperuricemia and associated renal inflammation in potassium oxonate and hypoxanthine-induced rat, Food Biosci. 51 (2023) 102311. https://doi.org/10.1016/j.fbio.2022.102311.
Y. Yuan, J.H. Zhou, Y.F. Zheng, et al., Beneficial effects of polysaccharide-rich extracts from Apocynum venetum leaves on hypoglycemic and gut microbiota in type 2 diabetic mice, Biomed. Pharmacother. 127 (2020) 110182. https://doi.org/10.1016/j.biopha.2020.110182.
J.M. Larsen, The immune response to Prevotella bacteria in chronic inflammatory disease, Immunology 151 (2017) 363-374. https://doi.org/10.1111/imm.12760.
C. Cao, B. Fan, J. Zhu, et al., Association of gut microbiota and biochemical features in a chinese population with renal uric acid stone, Front. Pharmacol. 13 (2022) 888883. https://doi.org/10.3389/fphar.2022.888883.
M.T. Liang, J.K. Liu, W.J. Chen, et al., Diagnostic model for predicting hyperuricemia based on alterations of the gut microbiome in individuals with different serum uric acid levels, Front. Endocrinol. 13 (2022) 925119. https://doi.org/10.3389/fendo.2022.925119.
H.Y. Zhao, X.Y. Chen, L. Zhang, et al., Lacticaseibacillus rhamnosus Fmb14 prevents purine induced hyperuricemia and alleviate renal fibrosis through gut-kidney axis, Pharmacol. Res. 182 (2022) 106350. https://doi.org/10.1016/j.phrs.2022.106350.
J.F. Mu, Q.L. Lin, Y. Liang, An update on the effects of food-derived active peptides on the intestinal microecology, Crit. Rev. Food Sci. Nutr. 63(33) (2022) 11625-11639. https://doi.org/10.1080/10408398.2022.2094889.
L.Y. Yun, W. Li, T. Wu, et al., Effect of sea cucumber peptides on the immune response and gut microbiota composition in ovalbumin-induced allergic mice, Food Funct. 13 (2022) 6338-6349. https://doi.org/10.1039/D2FO00536K.
Y.J. Guo, Y.N. Yu, H.L. Li, et al., Inulin supplementation ameliorates hyperuricemia and modulates gut microbiota in Uox-knockout mice, European Journal of Nutrition 60 (2021) 2217-2230. https://doi.org/10.1007/s00394-020-02414-x.
N.H. Zhang, J.X. Zhou, L. Zhao, et al., Ferulic acid supplementation alleviates hyperuricemia in high-fructose/fat diet-fed rats via promoting uric acid excretion and mediating the gut microbiota, Food Funct. 14 (2023) 1710-1725. https://doi.org/10.1039/d2fo03332a.
K. Wang, M.F. Liao, N. Zhou, et al., Parabacteroides distasonis alleviates obesity and metabolic dysfunctions via production of succinate and secondary bile acids, Cell Rep. 26 (2019) 222-235. https://doi.org/10.1016/j.celrep.2018.12.028.
F.d. Vadder, G. Mithieux, Gut-brain signaling in energy homeostasis: the unexpected role of microbiota-derived succinate, J. Endocrinol. 236 (2018) R105-r108. https://doi.org/10.1530/joe-17-0542.
Y. Liu, X.M. Sun, D.L. Di, et al., A metabolic profiling analysis of symptomatic gout in human serum and urine using high performance liquid chromatography-diode array detector technique, Clin. Chim. Acta 412 (2011) 2132-2140. https://doi.org/10.1016/j.cca.2011.07.031.
S.E. Perez-Pozo, J. Schold, T. Nakagawa, et al., Excessive fructose intake induces the features of metabolic syndrome in healthy adult men: role of uric acid in the hypertensive response, Int. J. Obes. 34 (2010) 454-461. https://doi.org/10.1038/ijo.2009.259.
L.Z. Agudelo, D.M.S. Ferreira, I. Cervenka, et al., Kynurenic acid and Gpr35 regulate adipose tissue energy homeostasis and inflammation, Cell Metab. 27 (2018) 378-392. https://doi.org/10.1016/j.cmet.2018.01.004.
H.B. He, X.B. Ren, X.Y. Wang, et al., Therapeutic effect of Yunnan Baiyao on rheumatoid arthritis was partially due to regulating arachidonic acid metabolism in osteoblasts, J. Pharm. Biomed. Anal. 59 (2012) 130-137. https://doi.org/10.1016/j.jpba.2011.10.019.
M.A. Belury, R.M. Cole, D.B. Snoke, et al., Linoleic acid, glycemic control and type 2 diabetes, Prostaglandins Leukot. Essent. Fatty Acids 132 (2018) 30-33. https://doi.org/10.1016/j.plefa.2018.03.001.
S. Takeda, T. Himeno, K. Kakizoe, et al., Cannabidiolic acid-mediated selective down-regulation of c-fos in highly aggressive breast cancer MDA-MB-231 cells: possible involvement of its down-regulation in the abrogation of aggressiveness, J. Nat. Med. 71 (2017) 286-291. https://doi.org/10.1007/s11418-016-1030-0.