{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T01:21:12Z","timestamp":1789608072076,"version":"build-2803163510"},"reference-count":35,"publisher":"Pharmaceutical Society of Japan","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biological &amp; Pharmaceutical Bulletin","Biol. Pharm. Bull."],"published-print":{"date-parts":[[2025,12,13]]},"DOI":"10.1248\/bpb.b25-00265","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T22:09:01Z","timestamp":1765577341000},"page":"1911-1920","source":"Crossref","is-referenced-by-count":1,"title":["Effect of Probiotics on Immunosuppressive Drug Pharmacokinetics: Interaction between &lt;i&gt;Bacillus subtilis&lt;\/i&gt; and Tacrolimus in Mice"],"prefix":"10.1248","volume":"48","author":[{"given":"Yuichi","family":"Tsuchiya","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Kyushu University Hospital, 3\u20131\u20131 Maidashi, Higashi-ku, Fukuoka 802\u20138582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanae","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Kyushu University Hospital, 3\u20131\u20131 Maidashi, Higashi-ku, Fukuoka 802\u20138582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Department of Infectious Medicine, Kurume University School of Medicine, 67 Asahimachi, Kurume, Fukuoka 830\u20130011, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshitoshi","family":"Ogura","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Department of Infectious Medicine, Kurume University School of Medicine, 67 Asahimachi, Kurume, Fukuoka 830\u20130011, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Hirota","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Kyushu University Hospital, 3\u20131\u20131 Maidashi, Higashi-ku, Fukuoka 802\u20138582, Japan"},{"name":"Department of Clinical Pharmacology and Biopharmaceutics, Graduate School of Medicine Sciences, Kyushu University, 3\u20131\u20131 Maidashi, Higashi-ku, Fukuoka 802\u20138582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ichiro","family":"Ieiri","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Kyushu University Hospital, 3\u20131\u20131 Maidashi, Higashi-ku, Fukuoka 802\u20138582, Japan"},{"name":"Department of Clinical Pharmacology and Biopharmaceutics, Graduate School of Medicine Sciences, Kyushu University, 3\u20131\u20131 Maidashi, Higashi-ku, Fukuoka 802\u20138582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayako","family":"Uchida","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Kyushu University Hospital, 3\u20131\u20131 Maidashi, Higashi-ku, Fukuoka 802\u20138582, Japan"},{"name":"Department of Clinical Pharmacology and Biopharmaceutics, Graduate School of Medicine Sciences, Kyushu University, 3\u20131\u20131 Maidashi, Higashi-ku, Fukuoka 802\u20138582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"163","reference":[{"key":"1","doi-asserted-by":"crossref","unstructured":"1) Kurata Y, Ieiri I, Kimura M, Morita T, Irie S, Urae A, Ohdo S, Ohtani H, Sawada Y, Higuchi S, Otsubo K. Role of human <i>MDR1<\/i> gene polymorphism in bioavailability and interaction of digoxin, a substrate of P-glycoprotein. <i>Clin. Pharmacol. Ther.<\/i>, <b>72<\/b>, 209\u2013219 (2002).","DOI":"10.1067\/mcp.2002.126177"},{"key":"2","doi-asserted-by":"crossref","unstructured":"2) Nishizato Y, Ieiri I, Suzuki H, Kimura M, Kawabata K, Hirota T, Takane H, Irie S, Kusuhara H, Urasaki Y, Urae A, Higuchi S, Otsubo K, Sugiyama Y. Polymorphisms of <i>OATP-C (SLC21A6)<\/i> and <i>OAT3 (SLC22A8)<\/i> genes: consequences for pravastatin pharmacokinetics. <i>Clin. Pharmacol. Ther.<\/i>, <b>73<\/b>, 554\u2013565 (2003).","DOI":"10.1016\/S0009-9236(03)00060-2"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3) Duarte JD, Cavallari LH. Pharmacogenetics to guide cardiovascular drug therapy. <i>Nat. Rev. Cardiol.<\/i>, <b>18<\/b>, 649\u2013665 (2021).","DOI":"10.1038\/s41569-021-00549-w"},{"key":"4","unstructured":"4) Daly AK. Pharmacogenetics: a general review on progress to date. <i>Br. Med. Bull.<\/i>, <b>124<\/b>, 65\u201379 (2017)."},{"key":"5","doi-asserted-by":"crossref","unstructured":"5) Lindenbaum J, Rund DG, Butler VP Jr, Tse-Eng D, Saha JR. Inactivation of digoxin by the gut flora: reversal by antibiotic therapy. <i>N. Engl. J. Med.<\/i>, <b>305<\/b>, 789\u2013794 (1981).","DOI":"10.1056\/NEJM198110013051403"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6) Peppercorn MA, Goldman P. The role of intestinal bacteria in the metabolism of salicylazosulfapyridine. <i>J. Pharmacol. Exp. Ther.<\/i>, <b>181<\/b>, 555\u2013562 (1972).","DOI":"10.1016\/S0022-3565(25)29238-2"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7) Guthrie L, Gupta S, Daily J, Kelly L. Human microbiome signatures of differential colorectal cancer drug metabolism. <i>NPJ Biofilms Microbiomes<\/i>, <b>3<\/b>, 27 (2017).","DOI":"10.1038\/s41522-017-0034-1"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8) Ladirat SE, Schols HA, Nauta A, Schoterman MHC, Keijser BJF, Montijn RC, Gruppen H, Schuren FHJ. High-throughput analysis of the impact of antibiotics on the human intestinal microbiota composition. <i>J. Microbiol. Methods<\/i>, <b>92<\/b>, 387\u2013397 (2013).","DOI":"10.1016\/j.mimet.2012.12.011"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9) Sekirov I, Russell SL, Caetano M, Antunes L, Finlay BB. Gut microbiota in health and disease. <i>Physiol. Rev.<\/i>, <b>90<\/b>, 859\u2013904 (2010).","DOI":"10.1152\/physrev.00045.2009"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10) Hou K, Wu ZX, Chen XY, Wang JQ, Zhang D, Xiao C, Zhu D, Koya JB, Wei L, Li J, Chen ZS. Microbiota in health and diseases. <i>Signal Transduct. Target. Ther.<\/i>, <b>7<\/b>, 135 (2022).","DOI":"10.1038\/s41392-022-00974-4"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11) Ohtsu T, Haruma K, Ide Y, Takagi A. The effect of continuous intake of <i>Lactobacillus gasseri<\/i> OLL2716 on mild to moderate delayed gastric emptying: a randomized controlled study. <i>Nutrients<\/i>, <b>13<\/b>, 1852 (2021).","DOI":"10.3390\/nu13061852"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12) Davani-Davari D, Negahdaripour M, Karimzadeh I, Seifan M, Mohkam M, Masoumi SJ, Berenjian A, Ghasemi Y. Prebiotics: definition, types, sources, mechanisms, and clinical applications. <i>Foods<\/i>, <b>8<\/b>, 92 (2019).","DOI":"10.3390\/foods8030092"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13) Azad MAK, Sarker M, Wan D. Immunomodulatory effects of probiotics on cytokine profiles. <i>BioMed Res. Int.<\/i>, <b>2018<\/b>, 8063647 (2018).","DOI":"10.1155\/2018\/8063647"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14) Asha MZ, Khalil SFH. Efficacy and safety of probiotics, prebiotics and synbiotics in the treatment of irritable bowel syndrome: a systematic review and meta-analysis. <i>Sultan Qaboos Univ. Med. J.<\/i>, <b>20<\/b>, e13\u2013e24 (2020).","DOI":"10.18295\/squmj.2020.20.01.003"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15) Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, Feldstein AE, Britt EB, Fu X, Chung YM, Wu Y, Schauer P, Smith JD, Allayee H, Tang WHW, Didonato JA, Lusis AJ, Hazen SL. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. <i>Nature<\/i>, <b>472<\/b>, 57\u201363 (2011).","DOI":"10.1038\/nature09922"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16) Howitt MR, Garrett WS. A complex microworld in the gut: gut microbiota and cardiovascular disease connectivity. <i>Nat. Med.<\/i>, <b>18<\/b>, 1188\u20131189 (2012).","DOI":"10.1038\/nm.2895"},{"key":"17","unstructured":"17) \u201cProbiotics in Food Beverages Dietary Supplements &amp; Animal Feed Market\u201d.: &lt;https:\/\/www.bccresearch.com\/market-research\/food-and-beverage\/probiotics-market-ingredients-supplements-foods-report.html&gt;, accessed 17 March, 2025."},{"key":"18","unstructured":"18) \u201cProbiotic usage increased following pandemic, says recent consumer survey\u201d.: &lt;https:\/\/www.nutritionaloutlook.com\/view\/probiotic-usage-increased-following-pandemic-says-recent-consumer-survey&gt;, accessed 23 March, 2025."},{"key":"19","doi-asserted-by":"crossref","unstructured":"19) Takada T, Chinda D, Mikami T, Shimizu K, Oana K, Hayamizu S, Miyazawa K, Arai T, Katto M, Nagara Y, Makino H, Kushiro A, Oishi K, Fukuda S. Dynamic analysis of human small intestinal microbiota after an ingestion of fermented milk by small-intestinal fluid perfusion using an endoscopic retrograde bowel insertion technique. <i>Gut Microbes<\/i>, <b>11<\/b>, 1662\u20131676 (2020).","DOI":"10.1080\/19490976.2020.1766942"},{"key":"20","doi-asserted-by":"crossref","unstructured":"20) Staatz CE, Tett SE. Clinical pharmacokinetics and pharmacodynamics of tacrolimus in solid organ transplantation. <i>Clin. Pharmacokinet.<\/i>, <b>43<\/b>, 623\u2013653 (2004).","DOI":"10.2165\/00003088-200443100-00001"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21) Undre NA, Van Hooff J, Christiaans M, Vanrenterghem Y, Donck J, Heeman U, Kohnle M, Zanker B, Land W, Morales JM, Andr\u00e9s A, Sch\u00e4fer A, Stevenson P. Low systemic exposure to tacrolimus correlates with acute rejection. <i>Transplant. Proc.<\/i>, <b>31<\/b>, 296\u2013298 (1999).","DOI":"10.1016\/S0041-1345(98)01633-9"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22) Kovarik JM, Tedesco H, Pascual J, Civati G, Bizot MN, Geissler J, Schmidli H. Everolimus therapeutic concentration range defined from a prospective trial with reduced-exposure cyclosporine in <i>de novo<\/i> kidney transplantation. <i>Ther. Drug Monit.<\/i>, <b>26<\/b>, 499\u2013505 (2004).","DOI":"10.1097\/00007691-200410000-00007"},{"key":"23","doi-asserted-by":"crossref","unstructured":"23) Foote CJ, Greer W, Kiberd B, Fraser A, Lawen J, Nashan B, Belitsky P. Polymorphisms of multidrug resistance gene (MDR1) and cyclosporine absorption in <i>de novo<\/i> renal transplant patients. <i>Transplantation<\/i>, <b>83<\/b>, 1380\u20131384 (2007).","DOI":"10.1097\/01.tp.0000264197.88129.2e"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24) Goto M, Masuda S, Kiuchi T, Ogura Y, Oike F, Okuda M, Tanaka K, Inui KI. <i>CYP3A5*1<\/i>-carrying graft liver reduces the concentration\/oral dose ratio of tacrolimus in recipients of living-donor liver transplantation. <i>Pharmacogenetics<\/i>, <b>14<\/b>, 471\u2013478 (2004).","DOI":"10.1097\/01.fpc.0000114747.08559.49"},{"key":"25","doi-asserted-by":"crossref","unstructured":"25) Uesugi M, Masuda S, Katsura T, Oike F, Takada Y, Inui KI. Effect of intestinal CYP3A5 on postoperative tacrolimus trough levels in living-donor liver transplant recipients. <i>Pharmacogenet. Genomics<\/i>, <b>16<\/b>, 119\u2013127 (2006).","DOI":"10.1097\/01.fpc.0000184953.31324.e4"},{"key":"26","doi-asserted-by":"crossref","unstructured":"26) Lee JR, Muthukumar T, Dadhania D, Taur Y, Jenq RR, Toussaint NC, Ling L, Pamer E, Suthanthiran M. Gut microbiota and tacrolimus dosing in kidney transplantation. <i>PLOS ONE<\/i>, <b>10<\/b>, e0122399 (2015).","DOI":"10.1371\/journal.pone.0122399"},{"key":"27","doi-asserted-by":"crossref","unstructured":"27) Guo Y, Crnkovic CM, Won KJ, Yang X, Lee JR, Orjala J, Lee H, Jeong H. Commensal gut bacteria convert the immunosuppressant tacrolimus to less potent metabolites. <i>Drug Metab. Dispos.<\/i>, <b>47<\/b>, 194\u2013202 (2019).","DOI":"10.1124\/dmd.118.084772"},{"key":"28","doi-asserted-by":"crossref","unstructured":"28) Zimmermann M, Zimmermann-Kogadeeva M, Wegmann R, Goodman AL. Separating host and microbiome contributions to drug pharmacokinetics and toxicity. <i>Science<\/i>, <b>363<\/b>, eaat9931 (2019).","DOI":"10.1126\/science.aat9931"},{"key":"29","doi-asserted-by":"crossref","unstructured":"29) Kanda Y. Investigation of the freely available easy-to-use software \u02bdEZR\u2019 for medical statistics. <i>Bone Marrow Transplant.<\/i>, <b>48<\/b>, 452\u2013458 (2013).","DOI":"10.1038\/bmt.2012.244"},{"key":"30","doi-asserted-by":"crossref","unstructured":"30) Iwasaki K. Metabolism of tacrolimus (FK506) and recent topics in clinical pharmacokinetics. <i>Drug Metab. Pharmacokinet.<\/i>, <b>22<\/b>, 328\u2013335 (2007).","DOI":"10.2133\/dmpk.22.328"},{"key":"31","doi-asserted-by":"crossref","unstructured":"31) Zimmermann M, Zimmermann-Kogadeeva M, Wegmann R, Goodman AL. Mapping human microbiome drug metabolism by gut bacteria and their genes. <i>Nature<\/i>, <b>570<\/b>, 462\u2013467 (2019).","DOI":"10.1038\/s41586-019-1291-3"},{"key":"32","doi-asserted-by":"crossref","unstructured":"32) Tron C, Petitcollin A, Verdier MC, Rayar M, Beaurepaire JM, Boudjema K, Bellissant E, Lemaitre F. Tacrolimus: does direct glucuronidation matter? An analytical and pharmacological perspective. <i>Pharmacol. Res.<\/i>, <b>124<\/b>, 164\u2013166 (2017).","DOI":"10.1016\/j.phrs.2017.03.027"},{"key":"33","doi-asserted-by":"crossref","unstructured":"33) Kuno T, Hirayama-Kurogi M, Ito S, Ohtsuki S. Effect of intestinal flora on protein expression of drug-metabolizing enzymes and transporters in the liver and kidney of germ-free and antibiotics-treated mice. <i>Mol. Pharm.<\/i>, <b>13<\/b>, 2691\u20132701 (2016).","DOI":"10.1021\/acs.molpharmaceut.6b00259"},{"key":"34","doi-asserted-by":"crossref","unstructured":"34) Toda T, Saito N, Ikarashi N, Ito K, Yamamoto M, Ishige A, Watanabe K, Sugiyama K. Intestinal flora induces the expression of Cyp3a in the mouse liver. <i>Xenobiotica<\/i>, <b>39<\/b>, 323\u2013334 (2009).","DOI":"10.1080\/00498250802651984"},{"key":"35","doi-asserted-by":"crossref","unstructured":"35) Xie Q, Zhang J, Liu M, Liu P, Wang Z, Zhu L, Jiang L, Jin M, Liu X, Liu L, Liu X. Short-chain fatty acids exert opposite effects on the expression and function of p-glycoprotein and breast cancer resistance protein in rat intestine. <i>Acta Pharmacol. Sin.<\/i>, <b>42<\/b>, 470\u2013481 (2021).","DOI":"10.1038\/s41401-020-0402-x"}],"container-title":["Biological and Pharmaceutical Bulletin"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/bpb\/48\/12\/48_b25-00265\/_pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T03:26:41Z","timestamp":1765596401000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/bpb\/48\/12\/48_b25-00265\/_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,13]]},"references-count":35,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025]]}},"URL":"https:\/\/doi.org\/10.1248\/bpb.b25-00265","relation":{},"ISSN":["0918-6158","1347-5215"],"issn-type":[{"value":"0918-6158","type":"print"},{"value":"1347-5215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,13]]},"article-number":"b25-00265"}}