{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T09:07:29Z","timestamp":1766048849011,"version":"3.48.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:00:00Z","timestamp":1761523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["25K21101"],"award-info":[{"award-number":["25K21101"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["23H05470"],"award-info":[{"award-number":["23H05470"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Diabetic nephropathy is a kidney disease aggravated by the uremic toxin indoxyl sulfate, which is produced from indole by the gut microbiota. Targeting the bacterial enzyme tryptophan indole-lyase (TIL), which produces indole from l-tryptophan, could be a promising therapeutic strategy. This study investigates diketopiperazines (DKPs), particularly cyclo-glycylproline [cyclo(Gly-Pro)], as potential TIL inhibitors. Cyclo(Gly-Pro) and other DKPs moderately inhibited indole production from l-tryptophan in crude bacterial extracts. Cyclo(Gly-Pro) was not metabolized by the bacteria and did not affect their viability. Cyclo(Gly-Pro) inhibited the Escherichia coli TIL with a Ki\u200b value of 17\u00a0\u03bcM through a mixed-type mechanism. Computational docking studies supported this finding, showing that cyclo(Gly-Pro) binds near the active site of TIL. Additionally, cyclo(Gly-Pro) significantly reduced indole production in bacterial cultures and human fecal samples. These findings suggest that cyclo(Gly-Pro) could be a promising dietary supplement or a lead compound for developing new therapeutics to prevent or treat diabetic nephropathy.<\/jats:p>","DOI":"10.1093\/bbb\/zbaf152","type":"journal-article","created":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T12:00:15Z","timestamp":1761393615000},"page":"57-65","source":"Crossref","is-referenced-by-count":0,"title":["Cyclo-glycylproline, a food-derived diketopiperazine, inhibits bacterial indole production: implications for diabetic nephropathy prevention"],"prefix":"10.1093","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9300-4849","authenticated-orcid":false,"given":"Daiki","family":"Oikawa","sequence":"first","affiliation":[{"name":"Tohoku University Department of Biomolecular Engineering, Graduate School of Engineering, , 6-6-11 Aoba, Aramaki, Aoba-ku, Sendai, Miyagi, 980-8579 \u00a0","place":["Japan"]},{"name":"Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University , Oiwake-cho, Kitashirakawa, Sakyo-ku, Kyoto, 606-8502 \u00a0","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5275-4731","authenticated-orcid":false,"given":"Toru","family":"Nakayama","sequence":"additional","affiliation":[{"name":"Tohoku University Department of Biomolecular Engineering, Graduate School of Engineering, , 6-6-11 Aoba, Aramaki, Aoba-ku, Sendai, Miyagi, 980-8579 \u00a0","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,10,27]]},"reference":[{"key":"2025121804021914600_bib1","doi-asserted-by":"publisher","first-page":"883","DOI":"10.3390\/molecules26040883","article-title":"Lignans of sesame (Sesamum indicum L.): a comprehensive 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