{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T20:15:53Z","timestamp":1781295353186,"version":"3.54.1"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":402,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Our bodies are home to individual-specific microbial ecosystems that have recently been found to be modified by cancer immunotherapies. The interaction between the gut microbiome and islet autoimmunity leading to type I diabetes (T1D) is well described and highlights the microbiome contribution during the onset and T1D development in animals and humans. As cancer immunotherapies induce gut microbiome perturbations and immune-mediated adverse events in susceptible patients, we hypothesized that NOD mice can be used as a predictive tool to investigate the effects of anti\u2013PD-1 treatment on the onset and severity of T1D, and how microbiota influences immunopathology. In this longitudinal study, we showed that anti\u2013PD-1 accelerated T1D onset, increased glutamic acid decarboxylase\u2013reactive T cell frequency in spleen, and precipitated destruction of \u03b2 cells, triggering high glucose levels and pancreatic islet reduction. Anti\u2013PD-1 treatment also resulted in temporal microbiota changes and lower diversity characteristic of T1D. Finally, we identified known insulin-resistance regulating bacteria that were negatively correlated with glucose levels, indicating that anti\u2013PD-1 treatment impacts the early gut microbiota composition. Moreover, an increase of mucin-degrading Akkermansia muciniphila points to alterations of barrier function and immune system activation. These results highlight the ability of microbiota to readily respond to therapy-triggered pathophysiological changes as rescuers (Bacteroides acidifaciens and Parabacteroides goldsteinii) or potential exacerbators (A. muciniphila). Microbiome-modulating interventions may thus be promising mitigation strategies for immunotherapies with high risk of immune-mediated adverse events.<\/jats:p>","DOI":"10.4049\/immunohorizons.2300103","type":"journal-article","created":{"date-parts":[[2023,12,26]],"date-time":"2023-12-26T14:37:32Z","timestamp":1703601452000},"page":"872-885","source":"Crossref","is-referenced-by-count":4,"title":["Gut Microbiota Is Associated with Onset and Severity of Type 1 Diabetes in Nonobese Diabetic Mice Treated with Anti\u2013PD-1"],"prefix":"10.1093","volume":"7","author":[{"given":"Shriram","family":"Patel","sequence":"first","affiliation":[{"name":"School of Microbiology and APC Microbiome Ireland, University College Cork , Cork , Ireland"},{"name":"SeqBiome Ltd , Cork ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenia","family":"Becker","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences, Roche Innovation Center Basel, Pharma Research & Early Development, Hoffmann-La Roche , Basel ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Ploix","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences, Roche Innovation Center Basel, Pharma Research & Early Development, Hoffmann-La Roche , Basel ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Steiner","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences, Roche Innovation Center Basel, Pharma Research & Early Development, Hoffmann-La Roche , Basel ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petar","family":"Scepanovic","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences, Roche Innovation Center Basel, Pharma Research & Early Development, Hoffmann-La Roche , Basel ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Fueth","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences, Roche Innovation Center Basel, Pharma Research & Early Development, Hoffmann-La Roche , Basel ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina","family":"de Vera Mudry","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences, Roche Innovation Center Basel, Pharma Research & Early Development, Hoffmann-La Roche , Basel ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7228-5928","authenticated-orcid":false,"given":"Anne","family":"Eichinger-Chapelon","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences, Roche Innovation Center Basel, Pharma Research & Early Development, Hoffmann-La Roche , Basel ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estelle","family":"Marrer-Berger","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences, Roche Innovation Center Basel, Pharma Research & Early Development, Hoffmann-La Roche , Basel ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus J","family":"Claesson","sequence":"additional","affiliation":[{"name":"School of Microbiology and APC Microbiome Ireland, University College Cork , Cork , Ireland"},{"name":"SeqBiome Ltd , Cork ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,12,26]]},"reference":[{"key":"2025010607440223200_r1","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.it.2006.02.001","article-title":"The PD-1-PD-L pathway in immunological tolerance","volume":"27","author":"Okazaki","year":"2006","journal-title":"Trends Immunol."},{"key":"2025010607440223200_r2","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1093\/annonc\/mdx108","article-title":"Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab","volume":"28","author":"Chaput","year":"2017","journal-title":"Ann. 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