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晚期胶质瘤与小鼠肠道细菌代谢物的有害改变有关。

Late-Stage Glioma Is Associated with Deleterious Alteration of Gut Bacterial Metabolites in Mice.

作者信息

Herbreteau Aglae, Aubert Philippe, Croyal Mikaël, Naveilhan Philippe, Billon-Crossouard Stéphanie, Neunlist Michel, Delneste Yves, Couez Dominique, Aymeric Laetitia

机构信息

University of Angers, Nantes Université, CHU Angers, Inserm, CNRS, CRCI2NA, SFR ICAT, F-49000 Angers, France.

Nantes Université, Inserm, TENS, The Enteric Nervous System in Gut and Brain Disorders, IMAD, F-44000 Nantes, France.

出版信息

Metabolites. 2022 Mar 25;12(4):290. doi: 10.3390/metabo12040290.

Abstract

Brain-gut axis refers to the bidirectional functional connection between the brain and the gut, which sustains vital functions for vertebrates. This connection also underlies the gastrointestinal (GI) comorbidities associated with brain disorders. Using a mouse model of glioma, based on the orthotopic injection of GL261 cell line in syngeneic C57BL6 mice, we show that late-stage glioma is associated with GI functional alteration and with a shift in the level of some bacterial metabolites in the cecum. By performing cecal content transfer experiments, we further show that cancer-associated alteration in cecal metabolites is involved in end-stage disease progression. Antibiotic treatment results in a slight but significant delay in mice death and a shift in the proportion of myeloid cells in the brain tumor environment. This work rationally considers microbiota modulating strategies in the clinical management of patients with late-stage glioma.

摘要

脑-肠轴是指大脑与肠道之间的双向功能连接,它维持着脊椎动物的重要功能。这种连接也是与脑部疾病相关的胃肠道合并症的基础。我们使用一种胶质瘤小鼠模型,该模型基于在同基因C57BL6小鼠中原位注射GL261细胞系,结果表明晚期胶质瘤与胃肠道功能改变以及盲肠中某些细菌代谢物水平的变化有关。通过进行盲肠内容物转移实验,我们进一步表明盲肠代谢物中与癌症相关的改变参与了终末期疾病的进展。抗生素治疗导致小鼠死亡略有但显著延迟,并且脑肿瘤环境中髓样细胞的比例发生变化。这项工作合理地考虑了晚期胶质瘤患者临床管理中的微生物群调节策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a370/9028041/e8b778f07f29/metabolites-12-00290-g001.jpg

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