Gut Microbiota Is Associated with Onset and Severity of Type 1 Diabetes in Nonobese Diabetic Mice Treated with Anti-PD-1.

Q3 Medicine
Shriram Patel, Eugenia Becker, Corinne Ploix, Guido Steiner, Petar Scepanovic, Matthias Fueth, Maria Cristina de Vera Mudry, Anne Eichinger-Chapelon, Estelle Marrer-Berger, Marcus J Claesson
{"title":"Gut Microbiota Is Associated with Onset and Severity of Type 1 Diabetes in Nonobese Diabetic Mice Treated with Anti-PD-1.","authors":"Shriram Patel, Eugenia Becker, Corinne Ploix, Guido Steiner, Petar Scepanovic, Matthias Fueth, Maria Cristina de Vera Mudry, Anne Eichinger-Chapelon, Estelle Marrer-Berger, Marcus J Claesson","doi":"10.4049/immunohorizons.2300103","DOIUrl":null,"url":null,"abstract":"<p><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-PD-1 treatment on the onset and severity of T1D, and how microbiota influences immunopathology. In this longitudinal study, we showed that anti-PD-1 accelerated T1D onset, increased glutamic acid decarboxylase-reactive T cell frequency in spleen, and precipitated destruction of β cells, triggering high glucose levels and pancreatic islet reduction. Anti-PD-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-PD-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.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10759162/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ImmunoHorizons","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.4049/immunohorizons.2300103","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0

Abstract

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-PD-1 treatment on the onset and severity of T1D, and how microbiota influences immunopathology. In this longitudinal study, we showed that anti-PD-1 accelerated T1D onset, increased glutamic acid decarboxylase-reactive T cell frequency in spleen, and precipitated destruction of β cells, triggering high glucose levels and pancreatic islet reduction. Anti-PD-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-PD-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.

肠道微生物群与抗 PD-1 治疗的非肥胖糖尿病小鼠 1 型糖尿病的发病和严重程度有关。
我们的身体是个体特异性微生物生态系统的家园,最近发现癌症免疫疗法改变了这些生态系统。肠道微生物组与导致I型糖尿病(T1D)的胰岛自身免疫之间的相互作用已被充分描述,并强调了微生物组在动物和人类T1D发病和发展过程中的作用。由于癌症免疫疗法会诱发肠道微生物组紊乱和易感患者免疫介导的不良事件,我们假设 NOD 小鼠可作为一种预测工具,用于研究抗 PD-1 治疗对 T1D 发病和严重程度的影响,以及微生物组如何影响免疫病理。在这项纵向研究中,我们发现抗-PD-1会加速T1D的发病,增加脾脏中谷氨酸脱羧酶反应性T细胞的频率,并促进β细胞的破坏,引发高血糖和胰岛功能减退。抗PD-1治疗也会导致T1D特有的时间性微生物群变化和多样性降低。最后,我们发现已知的胰岛素抵抗调节细菌与血糖水平呈负相关,这表明抗 PD-1 治疗影响了早期肠道微生物群的组成。此外,粘蛋白降解菌 Akkermansia muciniphila 的增加也表明屏障功能的改变和免疫系统的激活。这些结果突显了微生物群作为拯救者(Bacteroides acidifaciens 和 Parabacteroides goldsteinii)或潜在的加重者(A. muciniphila)对治疗引发的病理生理变化做出反应的能力。因此,微生物调节干预措施可能会成为具有免疫介导不良事件高风险的免疫疗法的有效缓解策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
3.70
自引率
0.00%
发文量
0
审稿时长
4 weeks
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信