{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T23:28:46Z","timestamp":1787873326584,"version":"build-2784847793"},"reference-count":41,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic kidney disease (CKD), a progressive disorder leading to renal dysfunction, remains a significant global health issue. This study investigated whether Lactiplantibacillus plantarum HY7718 modulates gut\u2013kidney axis-associated inflammatory, gastrointestinal, and microbial alterations in a mouse model of adenine-induced chronic kidney disease. We examined fibrosis- and inflammation-related gene expression in mouse tissues and analyzed the gut microbiota via next-generation sequencing. HY7718 supplementation was associated with reduced expression of genes related to renal fibrosis (Col1a1, Acta2) and vascular inflammation (Icam-1, Vcam-1). Further, HY7718 suppressed intestinal inflammatory responses, including downregulation of pro-inflammatory cytokines (Tnf, Il-1\u03b2, Il-6) and TLR4\/MyD88\/NF-\u03baB signaling pathway genes in the colon tissues. Gastrointestinal function was also improved, with significant upregulation of gastric motility-related genes and increased digestive enzyme activity. The gut microbiota composition was altered by HY7718, with reduced abundance of pro-inflammatory taxa such as Mucispirillum and Deferribacterota, whereas beneficial genera like Lactiplantibacillus were enriched. These microbial shifts were associated with reduced intestinal inflammatory and renal fibrosis-related markers. Overall, the findings indicate that HY7718 supplementation modulates gut\u2013kidney axis-associated inflammatory, gastrointestinal, and microbial alterations in adenine-induced CKD mice and supports further investigation of this strain in CKD-related settings.<\/jats:p>","DOI":"10.3390\/ijms27104348","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T16:26:37Z","timestamp":1778689597000},"page":"4348","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Lactiplantibacillus plantarum HY7718 Modulates Gut\u2013Kidney Axis-Associated Inflammation, Gastrointestinal Dysfunction, and Gut Microbiota in Adenine-Induced Chronic Kidney Disease Mice"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6923-6113","authenticated-orcid":false,"given":"Hyeonji","family":"Kim","sequence":"first","affiliation":[{"name":"R&BD Center, hy Co., Ltd., 22, Giheungdanji-ro 24beon-gil, Giheung-gu, Yongin-si 17086, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3305-7494","authenticated-orcid":false,"given":"Ji-Woong","family":"Jeong","sequence":"additional","affiliation":[{"name":"R&BD Center, hy Co., Ltd., 22, Giheungdanji-ro 24beon-gil, Giheung-gu, Yongin-si 17086, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5534-2871","authenticated-orcid":false,"given":"Joo-Yun","family":"Kim","sequence":"additional","affiliation":[{"name":"R&BD Center, hy Co., Ltd., 22, Giheungdanji-ro 24beon-gil, Giheung-gu, Yongin-si 17086, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Jung","family":"Shim","sequence":"additional","affiliation":[{"name":"R&BD Center, hy Co., Ltd., 22, Giheungdanji-ro 24beon-gil, Giheung-gu, Yongin-si 17086, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Hwan","family":"Lee","sequence":"additional","affiliation":[{"name":"R&BD Center, hy Co., Ltd., 22, Giheungdanji-ro 24beon-gil, Giheung-gu, Yongin-si 17086, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.kisu.2021.11.003","article-title":"Epidemiology of chronic kidney disease: An update 2022","volume":"12","author":"Kovesdy","year":"2022","journal-title":"Kidney Int. Suppl."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Deng, L., Guo, S., Liu, Y., Zhou, Y., Liu, Y., Zheng, X., Yu, X., and Shuai, P. (2025). Global, regional, and national burden of chronic kidney disease and its underlying etiologies from 1990 to 2021: A systematic analysis for the Global Burden of Disease Study 2021. BMC Public Health, 25.","DOI":"10.1186\/s12889-025-21851-z"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Dong, Y., and Tong, Y. (2025). The pathogenesis of chronic kidney disease (CKD) and the preventive and therapeutic effects of natural products. Curr. Issues Mol. Biol., 47.","DOI":"10.3390\/cimb47100853"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Zhang, J.-Q., Li, Y.-Y., Zhang, X.-Y., Tian, Z.-H., Liu, C., Wang, S.-T., and Zhang, F.-R. (2023). Cellular senescence of renal tubular epithelial cells in renal fibrosis. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1085605"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Tang, W., Liu, H., Li, X., and Deng, S. (2026). The key role and research progress of endothelial cells in renal microcirculation. Front. Med., 13.","DOI":"10.3389\/fmed.2026.1717495"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.7150\/ijbs.124499","article-title":"Microbiota-gut-kidney axis and targeted therapeutic strategies in kidney diseases","volume":"22","author":"Sun","year":"2026","journal-title":"Int. J. Biol. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1097\/MNH.0b013e328358c8d5","article-title":"CKD impairs barrier function and alters microbial flora of the intestine: A major link to inflammation and uremic toxicity","volume":"21","author":"Vaziri","year":"2012","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/s12964-021-00771-6","article-title":"TLR4 signaling in the development of colitis-associated cancer and its possible interplay with microRNA-155","volume":"19","author":"Guo","year":"2021","journal-title":"Cell Commun. Signal."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Huang, Y., Xin, W., Xiong, J., Yao, M., Zhang, B., and Zhao, J. (2022). The intestinal microbiota and metabolites in the gut-kidney-heart axis of chronic kidney disease. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.837500"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s11739-023-03374-w","article-title":"Gut microbiota, intestinal permeability, and systemic inflammation: A narrative review","volume":"19","author":"Petito","year":"2024","journal-title":"Intern. Emerg. Med."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Meijers, B., Farr\u00e9, R., Dejongh, S., Vicario, M., and Evenepoel, P. (2018). Intestinal barrier function in chronic kidney disease. Toxins, 10.","DOI":"10.3390\/toxins10070298"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1111\/sdi.13030","article-title":"Feeling gutted in chronic kidney disease (CKD): Gastrointestinal disorders and therapies to improve gastrointestinal health in individuals CKD, including those undergoing dialysis","volume":"37","author":"Biruete","year":"2024","journal-title":"Semin. Dial."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Karahan, D., and \u015eahin, \u0130. (2022). Comparison of gastrointestinal symptoms and findings in renal replacement therapy modalities. BMC Nephrol., 23.","DOI":"10.1186\/s12882-022-02893-6"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e2508029","DOI":"10.4014\/jmb.2508.08029","article-title":"Postbiotic potential of heat-killed Lacticaseibacillus paracasei HP7 in functional dyspepsia","volume":"35","author":"Lee","year":"2025","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Tian, N., Li, L., Ng, J.K.-C., and Li, P.K.-T. (2022). The potential benefits and controversies of probiotics use in patients at different stages of chronic kidney disease. Nutrients, 14.","DOI":"10.3390\/nu14194044"},{"key":"ref_16","first-page":"1","article-title":"Probiotics: Their potential to impact human health","volume":"36","author":"Sanders","year":"2007","journal-title":"Counc. Agric. Sci. Technol. Issue Pap."},{"key":"ref_17","first-page":"481651","article-title":"Health benefits of probiotics: A review","volume":"2013","author":"Kechagia","year":"2013","journal-title":"Int. Sch. Res. Not."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"106971","DOI":"10.1016\/j.imlet.2025.106971","article-title":"The benefits of Lactiplantibacillus plantarum: From immunomodulator to vaccine vector","volume":"272","author":"Tobias","year":"2025","journal-title":"Immunol. Lett."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Kim, H., Jeong, J.-W., Jeong, H., Lee, D., Gwon, H., Lee, K., Kim, J.-Y., Shim, J.-J., and Lee, J.-H. (2025). Lactiplantibacillus plantarum HY7718 attenuates renal injury in an adenine-induced chronic kidney disease mouse model via inhibition of inflammation and apoptosis. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262010052"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Maringhini, S., and Zoccali, C. (2024). Chronic kidney disease progression\u2014A challenge. Biomedicines, 12.","DOI":"10.3390\/biomedicines12102203"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Panizo, S., Mart\u00ednez-Arias, L., Alonso-Montes, C., Cannata, P., Mart\u00edn-Carro, B., Fern\u00e1ndez-Mart\u00edn, J.L., Naves-D\u00edaz, M., Carrillo-L\u00f3pez, N., and Cannata-And\u00eda, J.B. (2021). Fibrosis in chronic kidney disease: Pathogenesis and consequences. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010408"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2336128","DOI":"10.1080\/0886022X.2024.2336128","article-title":"Adenine-induced animal model of chronic kidney disease: Current applications and future perspectives","volume":"46","author":"Yang","year":"2024","journal-title":"Ren. Fail."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"C432","DOI":"10.1152\/ajpcell.00041.2018","article-title":"cAMP attenuates TGF-\u03b2\u2019s profibrotic responses in osteoarthritic synoviocytes: Involvement of hyaluronan and PRG4","volume":"315","author":"Qadri","year":"2018","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"H135","DOI":"10.1152\/ajpheart.00908.2024","article-title":"Endothelial dysfunction in chronic kidney disease: A clinical perspective","volume":"329","author":"Cho","year":"2025","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Roumeliotis, S., Mallamaci, F., and Zoccali, C. (2020). Endothelial dysfunction in chronic kidney disease, from biology to clinical outcomes: A 2020 update. J. Clin. Med., 9.","DOI":"10.3390\/jcm9082359"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1093\/ndt\/gfz055","article-title":"Most exposed: The endothelium in chronic kidney disease","volume":"35","author":"Hordijk","year":"2020","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1093\/ndt\/gfg080","article-title":"Impaired renal function is associated with markers of endothelial dysfunction and increased inflammatory activity","volume":"18","author":"Stam","year":"2003","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Alobaidi, S. (2025). The gut\u2013kidney axis in chronic kidney disease: Mechanisms, microbial metabolites, and microbiome-targeted therapeutics. Front. Med., 12.","DOI":"10.3389\/fmed.2025.1675458"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Zhao, Y., Wu, J., Liu, X., Chen, X., and Wang, J. (2025). Decoding nature: Multi-target anti-inflammatory mechanisms of natural products in the TLR4\/NF-\u03baB pathway. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1467193"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1111\/j.1600-065X.2012.01099.x","article-title":"NF-\u03baB and the link between inflammation and cancer","volume":"246","author":"DiDonato","year":"2012","journal-title":"Immunol. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1111\/jgh.13458","article-title":"Patients with chronic kidney disease have abnormal upper gastro-intestinal tract digestive function: A study of uremic enteropathy","volume":"32","author":"Grant","year":"2017","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1016\/j.suc.2011.06.012","article-title":"Gastric motility physiology and surgical intervention","volume":"91","author":"Rostas","year":"2011","journal-title":"Surg. Clin. N. Am."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Qiao, H., Cao, Y., Zhang, M., Zhang, X., and Li, P. (2025). Protective effects of aucubin in DSS-induced colitis: Modulation of inflammatory pathways, intestinal barrier integrity, and gut microbiota. Foods, 14.","DOI":"10.3390\/foods14213648"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Bhargava, S., Merckelbach, E., Noels, H., Vohra, A., and Jankowski, J. (2022). Homeostasis in the gut microbiota in chronic kidney disease. Toxins, 14.","DOI":"10.3390\/toxins14100648"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s00430-021-00702-9","article-title":"The human symbiont Mucispirillum schaedleri: Causality in health and disease","volume":"210","author":"Herp","year":"2021","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Vacca, M., Celano, G., Calabrese, F.M., Portincasa, P., Gobbetti, M., and De Angelis, M. (2020). The controversial role of human gut Lachnospiraceae. Microorganisms, 8.","DOI":"10.3390\/microorganisms8040573"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/s40168-025-02096-9","article-title":"Enhanced propionate and butyrate metabolism in cecal microbiota contributes to cold-stress adaptation in sheep","volume":"13","author":"Cheng","year":"2025","journal-title":"Microbiome"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e2411809121","DOI":"10.1073\/pnas.2411809121","article-title":"Tungsten is utilized for lactate consumption and SCFA production by a dominant human gut microbe Eubacterium limosum","volume":"122","author":"Putumbaka","year":"2025","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Gao, F., Cheng, C., Li, R., Chen, Z., Tang, K., and Du, G. (2025). The role of Akkermansia muciniphila in maintaining health: A bibliometric study. Front. Med., 12.","DOI":"10.3389\/fmed.2025.1484656"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"127019","DOI":"10.1016\/j.micres.2022.127019","article-title":"Lactobacillus and intestinal diseases: Mechanisms of action and clinical applications","volume":"260","author":"Huang","year":"2022","journal-title":"Microbiol. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"117754","DOI":"10.1016\/j.taap.2026.117754","article-title":"Multi-omics reveal the key role of gut microbiota metabolism in adenine-induced chronic kidney disease","volume":"509","author":"Xin","year":"2026","journal-title":"Toxicol. Appl. Pharmacol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/10\/4348\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T04:13:16Z","timestamp":1779250396000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/10\/4348"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,13]]},"references-count":41,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["ijms27104348"],"URL":"https:\/\/doi.org\/10.3390\/ijms27104348","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,13]]}}}