{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T13:52:12Z","timestamp":1785851532948,"version":"3.56.0"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Gastrointest Canc"],"DOI":"10.1007\/s12029-026-01499-7","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T14:26:06Z","timestamp":1779719166000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Association of Probiotics with Effectiveness of Nivolumab or Pembrolizumab in Patients with Esophageal Cancer Taking Proton Pump Inhibitors: A Multicenter Retrospective Study"],"prefix":"10.1007","volume":"57","author":[{"given":"Ayumi","family":"Fujimoto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuji","family":"Uozumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironori","family":"Fujii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Tamaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoaki","family":"Eto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikumi","family":"Yamaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Maehara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotoshi","family":"Iihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoaki","family":"Hatakeyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayako","family":"Higuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0626-7908","authenticated-orcid":false,"given":"Hitoshi","family":"Kawazoe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisakazu","family":"Ohtani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,25]]},"reference":[{"key":"1499_CR1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74:229\u201363. https:\/\/doi.org\/10.3322\/caac.21834.","journal-title":"CA Cancer J Clin"},{"key":"1499_CR2","unstructured":"Cancer Statistics in Japan. Cancer Information Services, Cancer type statistical information Esophageal cancer. National Cancer Center, Japan. https:\/\/ganjoho.jp\/public\/cancer\/esophagus\/patients.html [in Japanese]. Accessed Jun 2, 2025."},{"key":"1499_CR3","doi-asserted-by":"publisher","first-page":"393","DOI":"10.6004\/jnccn.2023.0019","volume":"21","author":"JA Ajani","year":"2023","unstructured":"Ajani JA, D\u2019Amico TA, Bentrem DJ, et al. Esophageal and esophagogastric junction cancers, version 2.2023, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2023;21:393\u2013422. https:\/\/doi.org\/10.6004\/jnccn.2023.0019.","journal-title":"J Natl Compr Canc Netw"},{"key":"1499_CR4","doi-asserted-by":"publisher","first-page":"1506","DOI":"10.1016\/S1470-2045(19)30626-6","volume":"20","author":"K Kato","year":"2019","unstructured":"Kato K, Cho BC, Takahashi M, et al. Nivolumab versus chemotherapy in patients with advanced oesophageal squamous cell carcinoma refractory or intolerant to previous chemotherapy (ATTRACTION-3): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019;20:1506\u201317. https:\/\/doi.org\/10.1016\/S1470-2045(19)30626-6.","journal-title":"Lancet Oncol"},{"key":"1499_CR5","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1056\/NEJMoa2111380","volume":"386","author":"Y Doki","year":"2022","unstructured":"Doki Y, Ajani JA, Kato K, et al. Nivolumab combination therapy in advanced esophageal squamous-cell carcinoma. N Engl J Med. 2022;386:449\u201362. https:\/\/doi.org\/10.1056\/NEJMoa2111380.","journal-title":"N Engl J Med"},{"key":"1499_CR6","doi-asserted-by":"publisher","first-page":"4138","DOI":"10.1200\/JCO.20.01888","volume":"38","author":"T Kojima","year":"2020","unstructured":"Kojima T, Shah MA, Muro K, et al. Randomized phase III KEYNOTE-181 study of pembrolizumab versus chemotherapy in advanced esophageal cancer. J Clin Oncol. 2020;38:4138\u201348. https:\/\/doi.org\/10.1200\/JCO.20.01888.","journal-title":"J Clin Oncol"},{"key":"1499_CR7","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1016\/S0140-6736(21)01234-4","volume":"398","author":"JM Sun","year":"2021","unstructured":"Sun JM, Shen L, Shah MA, et al. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. Lancet. 2021;398:759\u201371. https:\/\/doi.org\/10.1016\/S0140-6736(21)01234-4.","journal-title":"Lancet"},{"key":"1499_CR8","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1126\/science.aan3706","volume":"359","author":"B Routy","year":"2018","unstructured":"Routy B, Le Chatelier E, Derosa L, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 2018;359:91\u20137. https:\/\/doi.org\/10.1126\/science.aan3706.","journal-title":"Science"},{"key":"1499_CR9","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1126\/science.aac4255","volume":"350","author":"A Sivan","year":"2015","unstructured":"Sivan A, Corrales L, Hubert N, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015;350:1084\u20139. https:\/\/doi.org\/10.1126\/science.aac4255.","journal-title":"Science"},{"key":"1499_CR10","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1126\/science.aad1329","volume":"350","author":"M V\u00e9tizou","year":"2015","unstructured":"V\u00e9tizou M, Pitt JM, Daill\u00e8re R, et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science. 2015;350:1079\u201384. https:\/\/doi.org\/10.1126\/science.aad1329.","journal-title":"Science"},{"key":"1499_CR11","doi-asserted-by":"publisher","first-page":"1437","DOI":"10.1093\/annonc\/mdy103","volume":"29","author":"L Derosa","year":"2018","unstructured":"Derosa L, Hellmann MD, Spaziano M, et al. Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer. Ann Oncol. 2018;29:1437\u201344. https:\/\/doi.org\/10.1093\/annonc\/mdy103.","journal-title":"Ann Oncol"},{"key":"1499_CR12","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1016\/j.annonc.2020.01.006","volume":"31","author":"M Chalabi","year":"2020","unstructured":"Chalabi M, Cardona A, Nagarkar DR, et al. Efficacy of chemotherapy and atezolizumab in patients with non-small-cell lung cancer receiving antibiotics and proton pump inhibitors: pooled post hoc analyses of the OAK and Poplar trials. Ann Oncol. 2020;31:525\u201331. https:\/\/doi.org\/10.1016\/j.annonc.2020.01.006.","journal-title":"Ann Oncol"},{"key":"1499_CR13","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.716317","volume":"12","author":"Q Giordan","year":"2021","unstructured":"Giordan Q, Salleron J, Vallance C, Moriana C, Clement-Duchene C. Impact of antibiotics and proton pump inhibitors on efficacy and tolerance of anti-PD-1 immune checkpoint inhibitors. Front Immunol. 2021;12:716317. https:\/\/doi.org\/10.3389\/fimmu.2021.716317.","journal-title":"Front Immunol"},{"key":"1499_CR14","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1136\/gutjnl-2015-310376","volume":"65","author":"F Imhann","year":"2016","unstructured":"Imhann F, Bonder MJ, Vich Vila A, et al. Proton pump inhibitors affect the gut microbiome. Gut. 2016;65:740\u20138. https:\/\/doi.org\/10.1136\/gutjnl-2015-310376.","journal-title":"Gut"},{"key":"1499_CR15","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1136\/gutjnl-2015-310861","volume":"65","author":"MA Jackson","year":"2016","unstructured":"Jackson MA, Goodrich JK, Maxan ME, et al. Proton pump inhibitors alter the composition of the gut microbiota. Gut. 2016;65:749\u201356. https:\/\/doi.org\/10.1136\/gutjnl-2015-310861.","journal-title":"Gut"},{"key":"1499_CR16","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-58553-4","volume":"16","author":"R Preet","year":"2025","unstructured":"Preet R, Islam MA, Shim J, et al. Gut commensal Bifidobacterium-derived extracellular vesicles modulate the therapeutic effects of anti-PD-1 in lung cancer. Nat Commun. 2025;16:3500. https:\/\/doi.org\/10.1038\/s41467-025-58553-4.","journal-title":"Nat Commun"},{"key":"1499_CR17","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2022.2081010","volume":"11","author":"Y Tomita","year":"2022","unstructured":"Tomita Y, Goto Y, Sakata S, et al. Clostridium butyricum therapy restores the decreased efficacy of immune checkpoint blockade in lung cancer patients receiving proton pump inhibitors. Oncoimmunology. 2022;11:2081010. https:\/\/doi.org\/10.1080\/2162402X.2022.2081010.","journal-title":"Oncoimmunology"},{"key":"1499_CR18","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2022.120573","volume":"300","author":"F Hersi","year":"2022","unstructured":"Hersi F, Elgendy SM, Al Shamma SA, Altell RT, Sadiek O, Omar HA. Cancer immunotherapy resistance: the impact of microbiome-derived short-chain fatty acids and other emerging metabolites. Life Sci. 2022;300:120573. https:\/\/doi.org\/10.1016\/j.lfs.2022.120573.","journal-title":"Life Sci"},{"key":"1499_CR19","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1016\/S0140-6736(07)61602-X","volume":"370","author":"E von Elm","year":"2007","unstructured":"von Elm E, Altman DG, Egger M, Pocock SJ, G\u00f8tzsche PC, Vandenbroucke JP, et al. The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370:1453\u20137. https:\/\/doi.org\/10.1016\/S0140-6736(07)61602-X.","journal-title":"Lancet"},{"key":"1499_CR20","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","volume":"45","author":"EA Eisenhauer","year":"2009","unstructured":"Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline, version 1.1. Eur J Cancer. 2009;45:228\u201347. https:\/\/doi.org\/10.1016\/j.ejca.2008.10.026.","journal-title":"Eur J Cancer"},{"key":"1499_CR21","unstructured":"National Cancer Institute Common terminology criteria for adverse events (CTCAE). version 5.0. https:\/\/ctep.cancer.gov\/protocolDevelopment\/electronic_applications\/ctc.htm#ctc_40. Accessed June 15, 2025."},{"key":"1499_CR22","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1002\/sim.4780050306","volume":"5","author":"EL Korn","year":"1986","unstructured":"Korn EL. Censoring distributions as a measure of follow-up in survival analysis. Stat Med. 1986;5:255\u201360. https:\/\/doi.org\/10.1002\/sim.4780050306.","journal-title":"Stat Med"},{"key":"1499_CR23","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1218386","volume":"14","author":"H Li","year":"2023","unstructured":"Li H, Zhang L, Yang F, Zhao R, Li X, Li H. Impact of concomitant medications on the efficacy of immune checkpoint inhibitors: an umbrella review. Front Immunol. 2023;14:1218386. https:\/\/doi.org\/10.3389\/fimmu.2023.1218386.","journal-title":"Front Immunol"},{"key":"1499_CR24","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1080\/1750743X.2025.2491300","volume":"17","author":"M Shibano","year":"2025","unstructured":"Shibano M, Takahashi M, Nakatsukasa H, Ishigami Y, Toyokawa T, Taira K, et al. Proton pump inhibitors reduce nivolumab efficacy in unresectable advanced or recurrent gastric cancer. Immunotherapy. 2025;17:331\u20138. https:\/\/doi.org\/10.1080\/1750743X.2025.2491300.","journal-title":"Immunotherapy"},{"key":"1499_CR25","doi-asserted-by":"publisher","first-page":"1582","DOI":"10.1007\/s10147-025-02805-2","volume":"30","author":"M Takahashi","year":"2025","unstructured":"Takahashi M, Nakatsukasa H, Shibano M, Ishigami Y, Oka T, Tani Y, et al. Potassium-competitive acid blocker has more negative impacts on clinical outcomes in patients with non-small cell lung cancer treated with checkpoint inhibitors than those of proton pump inhibitors. Int J Clin Oncol. 2025;30:1582\u201392. https:\/\/doi.org\/10.1007\/s10147-025-02805-2.","journal-title":"Int J Clin Oncol"},{"key":"1499_CR26","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14102395","volume":"14","author":"S Matsumura","year":"2022","unstructured":"Matsumura S, Ishikawa T, Yoshida J, et al. Proton pump inhibitors enhance the antitumor effect of chemotherapy for esophageal squamous cell carcinoma. Cancers (Basel). 2022;14:2395. https:\/\/doi.org\/10.3390\/cancers14102395.","journal-title":"Cancers (Basel)"}],"container-title":["Journal of Gastrointestinal Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12029-026-01499-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12029-026-01499-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12029-026-01499-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T14:26:07Z","timestamp":1779719167000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12029-026-01499-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,25]]},"references-count":26,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1499"],"URL":"https:\/\/doi.org\/10.1007\/s12029-026-01499-7","relation":{},"ISSN":["1941-6636"],"issn-type":[{"value":"1941-6636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,25]]},"assertion":[{"value":"6 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study protocol was approved by the Ethics Committee of Keio University School of Medicine (Approval No. 20241052). Permission to conduct this study was obtained from each facility. The study was conducted in accordance with the principles of the Declaration of Helsinki and the Ethical Guidelines for Medical and Health Research Involving Human Subjects of the Ministry of Education, Culture, Sports, Science, and Technology, and the Ministry of Health, Labour, and Welfare of Japan.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"The requirement for written informed consent was waived by the ethics review committee due to the study\u2019s retrospective design. Accordingly, we provided patients with an opt-out option via each hospital\u2019s official website.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"125"}}