{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:00:46Z","timestamp":1790838046592,"version":"4.1.0"},"reference-count":47,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T00:00:00Z","timestamp":1598400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000646","name":"Japan Society for the Promotion of Science London","doi-asserted-by":"publisher","award":["18K08198"],"award-info":[{"award-number":["18K08198"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003382","name":"Core Research for Evolutional Science and Technology","doi-asserted-by":"publisher","award":["JP19gm1010009"],"award-info":[{"award-number":["JP19gm1010009"]}],"id":[{"id":"10.13039\/501100003382","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009024","name":"Exploratory Research for Advanced Technology","doi-asserted-by":"publisher","award":["JPMJER1902"],"award-info":[{"award-number":["JPMJER1902"]}],"id":[{"id":"10.13039\/501100009024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","award":["S.F."],"award-info":[{"award-number":["S.F."]}],"id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016974","name":"Food Science Institute Foundation","doi-asserted-by":"publisher","award":["S.F."],"award-info":[{"award-number":["S.F."]}],"id":[{"id":"10.13039\/100016974","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Program for the Advancement of Research in Core Projects under Keio University\u2019s Longevity Initiative","award":["S.F."],"award-info":[{"award-number":["S.F."]}]},{"DOI":"10.13039\/100008695","name":"Japan Foundation for Applied Enzymology","doi-asserted-by":"publisher","award":["E.M."],"award-info":[{"award-number":["E.M."]}],"id":[{"id":"10.13039\/100008695","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Japan Health Foundation","award":["E.M."],"award-info":[{"award-number":["E.M."]}]},{"name":"HIROMI Medical Research Foundation","award":["E.M."],"award-info":[{"award-number":["E.M."]}]},{"name":"Okinaka Memorial Institute for Medical Research Grant","award":["E.M."],"award-info":[{"award-number":["E.M."]}]},{"name":"Tohoku University Center for Gender Equality Promotion (TUMUG) Support Project","award":["E.M."],"award-info":[{"award-number":["E.M."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Alterations in microbiota are known to affect kidney disease conditions. We have previously shown that germ-free conditions exacerbated adenine-induced kidney damage in mice; however, the mechanism by which this occurs has not been elucidated. To explore this mechanism, we examined the influence of germ-free conditions on purine metabolism and renal immune responses involved in the kidney damage. Germ-free mice showed higher expression levels of purine-metabolizing enzymes such as xanthine dehydrogenase, which converts adenine to a nephrotoxic byproduct 2,8-dihydroxyadenine (2,8-DHA). The germ-free mice also showed increased urinary excretion of allantoin, indicating enhanced purine metabolism. Metabolome analysis demonstrated marked differences in the purine metabolite levels in the feces of germ-free mice and mice with microbiota. Furthermore, unlike the germ-free condition, antibiotic treatment did not increase the expression of purine-metabolizing enzymes or exacerbate adenine-induced kidney damage. Considering renal immune responses, the germ-free mice displayed an absence of renal IL-17A expression. However, the adenine-induced kidney damage in wild-type mice was comparable to that in IL-17A-deficient mice, suggesting that IL-17A does not play a major role in the disease condition. Our results suggest that the enhanced host purine metabolism in the germ-free mice potentially promotes the conversion of the administered adenine into 2,8-DHA, resulting in exacerbated kidney damage. This further suggests a role of the microbiota in regulating host purine metabolism.<\/jats:p>","DOI":"10.3390\/toxins12090547","type":"journal-article","created":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T09:05:37Z","timestamp":1598432737000},"page":"547","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Germ-Free Conditions Modulate Host Purine Metabolism, Exacerbating Adenine-Induced Kidney Damage"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3706-2745","authenticated-orcid":false,"given":"Eikan","family":"Mishima","sequence":"first","affiliation":[{"name":"Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariko","family":"Ichijo","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Kawabe","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Kikuchi","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukako","family":"Akiyama","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7655-3005","authenticated-orcid":false,"given":"Takafumi","family":"Toyohara","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takehiro","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chitose","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuko","family":"Asao","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoto","family":"Ishii","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5161-9880","authenticated-orcid":false,"given":"Shinji","family":"Fukuda","sequence":"additional","affiliation":[{"name":"Institute for Advanced Biosciences, Keio University, Tsuruoka 997-0052, Japan"},{"name":"Intestinal Microbiota Project, Kanagawa Institute of Industrial Science and Technology, Kawasaki 210-0821, Japan"},{"name":"Transborder Medical Research Center, University of Tsukuba, Tsukuba 305-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaaki","family":"Abe","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan"},{"name":"Division of Medical Science, Tohoku University Graduate School of Biomedical Engineering, Sendai 980-8574, Japan"},{"name":"Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1038\/s41581-018-0018-2","article-title":"The gut microbiota and the brain-gut-kidney axis in hypertension and chronic kidney disease","volume":"14","author":"Yang","year":"2018","journal-title":"Nat. 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