Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 30030, China.
Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Psychopharmacology (Berl). 2020 Jul;237(7):2089-2101. doi: 10.1007/s00213-020-05520-0. Epub 2020 Jun 3.
Approximately 20-40% of patients with cancer will experience brain metastasis (BM), which has a great impact on the quality of life and survival rates of patients. Whole brain radiotherapy (WBRT) is an effective method for the treatment of BM. However, it cannot be ignored that WBRT might induce a series of neuropsychiatric side effects, including cognitive dysfunction (CD). Accumulating evidence shows that the gut microbiota and the gut-microbiota-brain axis may play a vital role in the pathogenesis of CD.
We adopted WBRT to mimic CD after a hierarchical cluster analysis of the Morris water maze test (MWMT) results. In addition, we observed the effects of antibiotics and prebiotics on WBRT-induced CD. Variations were revealed via the 16S rRNA sequencing analysis at different levels.
The 16S rRNA sequencing analysis revealed an altered composition of gut microbiota between CD and non-CD phenotypes. Furthermore, we observed a decrease in the levels of Phylum-Bacteroidete, Class-Bacteroidia, and Order-Bacteroidales in the CD group and an increase in the Genus-Allobaculum level after WBRT. Pretreatment with antibiotics caused a significant decrease in the level of Phylum-TM7 01, whereas an increase in the levels of Class-Gammaproteobacteria, Order-Enterobacteriales, and Species-Escherichia coli. After pretreatment with probiotics, the levels of Phylum-Cyanobacteria, Class-4C0d-2, and Order-YS2 were decreased, while the levels of Family-Bacteroidaceae, Genus-Bacteroides, and Species-Parabacteroides distasonis were increased.
WBRT-induced CD might be highly related to abnormal composition of gut microbiota. Strategies improving the composition of the gut microbiota may provide beneficial effects on CD in individuals exposed to WBRT.
约 20-40%的癌症患者会发生脑转移（BM），这极大地影响了患者的生活质量和生存率。全脑放疗（WBRT）是治疗 BM 的有效方法。然而，不容忽视的是，WBRT 可能会引起一系列神经精神副作用，包括认知功能障碍（CD）。越来越多的证据表明，肠道微生物群和肠道微生物群-脑轴可能在 CD 的发病机制中发挥重要作用。
我们采用 WBRT 模拟 Morris 水迷宫测试（MWMT）结果的层次聚类分析后的 CD。此外，我们观察了抗生素和益生元对 WBRT 诱导的 CD 的影响。通过 16S rRNA 测序分析在不同水平上揭示了变化。
16S rRNA 测序分析揭示了 CD 和非 CD 表型之间肠道微生物群组成的改变。此外，我们观察到 CD 组中门-Bacteroidetes、纲-Bacteroidia 和目-Bacteroidales 的水平降低，WBRT 后属-Allobaculum 的水平升高。抗生素预处理导致门-TM7 01 的水平显著降低，而 Class-Gammaproteobacteria、Order-Enterobacteriales 和 Species-Escherichia coli 的水平升高。益生菌预处理后，门-Cyanobacteria、纲-4C0d-2 和目-YS2 的水平降低，而科-Bacteroidaceae、属-Bacteroides 和种-Parabacteroides distasonis 的水平升高。
WBRT 诱导的 CD 可能与肠道微生物群的异常组成高度相关。改善肠道微生物群组成的策略可能对接受 WBRT 的个体的 CD 有益。
