{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:48:47Z","timestamp":1785437327097,"version":"3.56.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T00:00:00Z","timestamp":1664496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017599","name":"Science and Technology Program of Zhejiang Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100017599","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017599","name":"Science and Technology Program of Zhejiang Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100017599","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:p>Hyperuricemia is the main cause of gout and involved in the occurrence of multiple diseases, such as hypertension, metabolic disorders and chronic kidney disease. Emerging evidence suggests that lactic acid bacteria (LAB) have shown the beneficial effects on the prevention or treatment of hyperuricemia. In this study, the urate-lowering effect of two LAB strains, <jats:italic>Lacticaseibacillus rhamnosus<\/jats:italic> 1155 (LR1155) and <jats:italic>Limosilactobacillus fermentum<\/jats:italic> 2644 (LF2644) on hyperuricemic rats were investigated. A hyperuricemic rat model was induced by the intragastric treatment of potassium oxonate, combined with a high purine diet. The oral administration of LR1155, LF2644, or a combination of LR1155 and LF2644 for 4 weeks significantly prevented the rise of the serum uric acid (UA) induced by hyperuricemia. LR1155 and LF2644 significantly elevated the fecal UA levels, increased the UA content and up-regulated gene expression of UA transporter, ATP-binding cassette subfamily G-2 (ABCG2), in colon and jejunum tissues, suggesting the accelerated UA excretion from the intestine. Besides, LR1155 significantly inhibited the activity of xanthine oxidase (XOD) in liver and serum, benefited the reduce of UA production. In addition, LF2644 strengthened the gut barrier functions through an up-regulation of the gene expressions for occluding and mucin2, accompanied with the reduced inflammatory indicators of lipopolysaccharide (LPS) and interleukin-1\u03b2 (IL-1\u03b2) in hyperuricemic rat. Moreover, using 16s rDNA high-throughput sequencing of feces, LR1155 was shown to improve the hyperuricemia induced gut microbial dysbiosis. The genera <jats:italic>Roseburia<\/jats:italic>, <jats:italic>Butyricicoccus<\/jats:italic>, <jats:italic>Prevotella<\/jats:italic>, <jats:italic>Oscillibacter<\/jats:italic>, and <jats:italic>Bifidobacterium<\/jats:italic> may associate with the effect of LR1155 on microbiota in hyperuricemic rats. Collectively, the results indicated that LR1155 and LF2644 exhibit urate-lowering effects and could be used alone or in combination as a new adjuvant treatment for hyperuricemia.<\/jats:p>","DOI":"10.3389\/fnut.2022.993951","type":"journal-article","created":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T10:33:56Z","timestamp":1664534036000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":32,"title":["Probiotic effects of Lacticaseibacillus rhamnosus 1155 and Limosilactobacillus fermentum 2644 on hyperuricemic rats"],"prefix":"10.3389","volume":"9","author":[{"given":"Yanjun","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guodong","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunxia","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lie","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuoguo","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/2914019","article-title":"Effects and mechanisms of Dendrobium officinalis six nostrum for treatment of hyperuricemia with hyperlipidemia.","volume":"2020","author":"Guo","year":"2020","journal-title":"Evid Based Complement Alternat Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"564","DOI":"10.3390\/antiox10040564","article-title":"Anti-inflammatory and anti-hyperuricemic effects of chrysin on a high fructose corn syrup-induced hyperuricemia rat model via the amelioration of urate transporters and inhibition of NLRP3 inflammasome signaling pathway.","volume":"10","author":"Chang","year":"2021","journal-title":"Antioxidants."},{"key":"B3","first-page":"3167","article-title":"Update on the epidemiology, genetics, and therapeutic options of hyperuricemia.","volume":"12","author":"Li","year":"2020","journal-title":"Am J Transl Res."},{"key":"B4","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1186\/s41256-020-00178-9","article-title":"Geographical distribution of hyperuricemia in mainland China: a comprehensive systematic review and meta-analysis.","volume":"5","author":"Huang","year":"2020","journal-title":"Glob Health Res Policy."},{"key":"B5","doi-asserted-by":"publisher","first-page":"312","DOI":"10.5114\/reum.2020.100140","article-title":"Pathophysiology of hyperuricemia and its clinical significance \u2013 a narrative review.","volume":"58","author":"Skoczy\u0144ska","year":"2020","journal-title":"Reumatologia."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2018.00160","article-title":"Physiology of hyperuricemia and urate-lowering treatments.","volume":"5","author":"Benn","year":"2018","journal-title":"Front Med (Lausanne)."},{"key":"B7","doi-asserted-by":"publisher","first-page":"610","DOI":"10.3390\/md18120610","article-title":"Anti-hyperuricemic effects of astaxanthin by regulating xanthine oxidase, adenosine deaminase and urate transporters in rats.","volume":"18","author":"Le","year":"2020","journal-title":"Mar Drugs."},{"key":"B8","doi-asserted-by":"publisher","first-page":"4642","DOI":"10.1038\/ncomms5642","article-title":"Early-onset metabolic syndrome in mice lacking the intestinal uric acid transporter SLC2A9.","volume":"5","author":"DeBosch","year":"2014","journal-title":"Nat Commun."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0030456","article-title":"Extra-renal elimination of uric acid via intestinal efflux transporter BCRP\/ABCG2.","volume":"7","author":"Hosomi","year":"2012","journal-title":"PLoS One."},{"key":"B10","doi-asserted-by":"publisher","first-page":"3151","DOI":"10.1080\/13880209.2016.1195847","article-title":"Uric acid transporters hiding in the intestine.","volume":"54","author":"Xu","year":"2016","journal-title":"Pharm Biol."},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.845684","article-title":"The role of the intestine in the development of hyperuricemia.","volume":"13","author":"Yin","year":"2022","journal-title":"Front Immunol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1038\/ncomms1756","article-title":"Decreased extra-renal urate excretion is a common cause of hyperuricemia.","volume":"3","author":"Ichida","year":"2012","journal-title":"Nat Commun."},{"key":"B13","doi-asserted-by":"publisher","first-page":"33082","DOI":"10.1038\/srep33082","article-title":"Comparative efficacy and safety of urate-lowering therapy for the treatment of hyperuricemia: a systematic review and network meta-analysis.","volume":"6","author":"Li","year":"2016","journal-title":"Sci Rep."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1186\/s42358-019-0080-x","article-title":"Benzbromarone in the treatment of gout.","volume":"59","author":"Azevedo","year":"2019","journal-title":"Adv Rheumatol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.jaad.2007.08.036","article-title":"Allopurinol is the most common cause of Stevens-Johnson syndrome and toxic epidermal necrolysis in Europe and Israel.","volume":"58","author":"Halevy","year":"2008","journal-title":"J Am Acad Dermatol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"527","DOI":"10.3899\/jrheum.18076","article-title":"Hepatic safety of febuxostat compared with allopurinol in gout patients with fatty liver disease.","volume":"46","author":"Lee","year":"2019","journal-title":"J Rheumatol."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/srep20602","article-title":"Intestinal microbiota distinguish gout patients from healthy humans.","volume":"6","author":"Guo","year":"2016","journal-title":"Sci Rep."},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2017.00268","article-title":"Combined signature of the fecal microbiome and metabolome in patients with gout.","volume":"8","author":"Shao","year":"2017","journal-title":"Front Microbiol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"159","DOI":"10.4172\/2329-8901.1000159","article-title":"Probiotic Lactobacillus species strengthen intestinal barrier function and tight junction integrity in experimental necrotizing enterocolitis.","volume":"5","author":"Blackwood","year":"2017","journal-title":"J Probiotics Health."},{"key":"B20","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1038\/s41575-019-0173-3","article-title":"Probiotics and prebiotics in intestinal health and disease: from biology to the clinic.","volume":"16","author":"Sanders","year":"2019","journal-title":"Nat Rev Gastroenterol Hepatol."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0105577","article-title":"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.","volume":"9","author":"Li","year":"2014","journal-title":"PLoS One."},{"key":"B22","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3390\/microorganisms5010010","article-title":"Lactobacillus gasseri PA-3 uses the purines IMP, inosine and hypoxanthine and reduces their absorption in rats.","volume":"5","author":"Yamada","year":"2017","journal-title":"Microorganisms."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/19490976.2021.1897211","article-title":"Limosilactobacillus fermentum JL-3 isolated from \u201cJiangshui\u201d ameliorates hyperuricemia by degrading uric acid.","volume":"13","author":"Wu","year":"2021","journal-title":"Gut Microbes."},{"key":"B24","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.nut.2018.11.018","article-title":"Lactobacillus brevis DM9218 ameliorates fructose-induced hyperuricemia through inosine degradation and manipulation of intestinal dysbiosis.","volume":"62","author":"Wang","year":"2019","journal-title":"Nutrition."},{"key":"B25","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1016\/j.jfda.2016.07.003","article-title":"Evaluating the urate-lowering effects of different microbial fermented extracts in hyperuricemic models accompanied with a safety study.","volume":"25","author":"Chen","year":"2017","journal-title":"J Food Drug Anal."},{"key":"B26","doi-asserted-by":"publisher","first-page":"2032","DOI":"10.1016\/j.jchromb.2009.05.037","article-title":"A sensitive and specific liquid chromatography-tandem mass spectrometry method for the determination of intracellular and extracellular uric acid.","volume":"877","author":"Kim","year":"2009","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.110765","article-title":"Dendrobium officinalis six nostrum ameliorates urate under-excretion and protects renal dysfunction in lipid emulsion-induced hyperuricemic rats.","volume":"132","author":"Chen","year":"2020","journal-title":"Biomed Pharmacother."},{"key":"B28","doi-asserted-by":"publisher","first-page":"7900","DOI":"10.1039\/c9fo02032b","article-title":"Stevia residue extract increases intestinal uric acid excretion via interactions with intestinal urate transporters in hyperuricemic mice.","volume":"10","author":"Mehmood","year":"2019","journal-title":"Food Funct."},{"key":"B29","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1080\/15257770.2019.1694684","article-title":"ABCG2 expression and uric acid metabolism of the intestine in hyperuricemia model rat.","volume":"39","author":"Morimoto","year":"2020","journal-title":"Nucleosides Nucleotides Nucleic Acids."},{"key":"B30","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1039\/d1fo03723d","article-title":"Oral administration of Lactococcus lactis WHH2078 alleviates depressive and anxiety symptoms in mice with induced chronic stress.","volume":"13","author":"Gao","year":"2022","journal-title":"Food Funct."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1550","DOI":"10.21037\/atm-21-5052","article-title":"Hyperuricemia prevalence and its association with metabolic disorders: a multicenter retrospective real-world study in China.","volume":"9","author":"Pang","year":"2021","journal-title":"Ann Transl Med."},{"key":"B32","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1097\/MNH.0b013e32835ddad2","article-title":"The kidney in hyperuricemia and gout.","volume":"22","author":"Mount","year":"2013","journal-title":"Curr Opin Nephrol Hypertens."},{"key":"B33","doi-asserted-by":"publisher","first-page":"F991","DOI":"10.1152\/ajprenal.00283.2001","article-title":"Hyperuricemia induces a primary renal arteriolopathy in rats by a blood pressure-independent mechanism.","volume":"282","author":"Mazzali","year":"2002","journal-title":"Am J Physiol Renal Physiol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/1758-5996-4-12","article-title":"High plasma uric acid concentration: causes and consequences.","volume":"4","author":"de Oliveira","year":"2012","journal-title":"Diabetol Metab Syndr."},{"key":"B35","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1186\/s12986-017-0190-6","article-title":"Cichorium intybus L. promotes intestinal uric acid excretion by modulating ABCG2 in experimental hyperuricemia.","volume":"14","author":"Wang","year":"2017","journal-title":"Nutr Metab (Lond)."},{"key":"B36","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/j.ajps.2019.10.002","article-title":"Pharmacologic inducers of the uric acid exporter ABCG2 as potential drugs for treatment of gouty arthritis.","volume":"15","author":"Ristic","year":"2020","journal-title":"Asian J Pharm Sci."},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.8664","article-title":"The altered gut microbiota of high-purine-induced hyperuricemia rats and its correlation with hyperuricemia.","volume":"8","author":"Liu","year":"2020","journal-title":"PeerJ."},{"key":"B38","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.anaerobe.2014.08.010","article-title":"Butyricicoccus pullicaecorum, a butyrate producer with probiotic potential, is intrinsically tolerant to stomach and small intestine conditions.","volume":"30","author":"Geirnaert","year":"2014","journal-title":"Anaerobe."},{"key":"B39","doi-asserted-by":"publisher","first-page":"157","DOI":"10.2217\/fmb-2016-0130","article-title":"Roseburia spp.: a marker of health?","volume":"12","author":"Tamanai-Shacoori","year":"2017","journal-title":"Future Microbiol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1038\/oby.2009.167","article-title":"Microbiota and SCFA in lean and overweight healthy subjects.","volume":"18","author":"Schwiertz","year":"2010","journal-title":"Obesity (Silver Spring)."},{"key":"B41","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1016\/j.chom.2019.07.004","article-title":"Obese individuals with and without Type 2 diabetes show different gut microbial functional capacity and composition.","volume":"26","author":"Thingholm","year":"2019","journal-title":"Cell Host Microbe."},{"key":"B42","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1186\/s10020-021-00311-5","article-title":"Taxonomic variations in the gut microbiome of gout patients with and without tophi might have a functional impact on urate metabolism.","volume":"27","author":"M\u00e9ndez-Salazar","year":"2021","journal-title":"Mol Med."},{"key":"B43","doi-asserted-by":"publisher","first-page":"3979","DOI":"10.1080\/10408398.2021.1874287","article-title":"The gut microbiota as a target to control hyperuricemia pathogenesis: potential mechanisms and therapeutic strategies.","volume":"62","author":"Wang","year":"2022","journal-title":"Crit Rev Food Sci Nutr."},{"key":"B44","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1111\/imr.12833","article-title":"Urate-induced immune programming: consequences for gouty arthritis and hyperuricemia.","volume":"294","author":"Cab\u0103u","year":"2020","journal-title":"Immunol Rev."},{"key":"B45","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/s41584-019-0334-3","article-title":"Asymptomatic hyperuricaemia: a silent activator of the innate immune system.","volume":"16","author":"Joosten","year":"2020","journal-title":"Nat Rev Rheumatol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1761","DOI":"10.2337\/db06-1491","article-title":"Metabolic endotoxemia initiates obesity and insulin resistance.","volume":"56","author":"Cani","year":"2007","journal-title":"Diabetes."},{"key":"B47","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1038\/nri2653","article-title":"Intestinal mucosal barrier function in health and disease.","volume":"9","author":"Turner","year":"2009","journal-title":"Nat Rev Immunol."},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.01953","article-title":"Probiotic Lactobacillus plantarum promotes intestinal barrier function by strengthening the epithelium and modulating gut microbiota.","volume":"9","author":"Wang","year":"2018","journal-title":"Front Microbiol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"1909","DOI":"10.3390\/cells9081909","article-title":"The intestinal barrier and current techniques for the assessment of gut permeability.","volume":"9","author":"Schoultz","year":"2020","journal-title":"Cells."},{"key":"B50","doi-asserted-by":"publisher","first-page":"2232","DOI":"10.1136\/gutjnl-2020-322260","article-title":"Mucus barrier, mucins and gut microbiota: the expected slimy partners?","volume":"69","author":"Paone","year":"2020","journal-title":"Gut."}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2022.993951\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T10:34:00Z","timestamp":1664534040000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2022.993951\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,30]]},"references-count":50,"alternative-id":["10.3389\/fnut.2022.993951"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2022.993951","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,30]]},"article-number":"993951"}}