Whole brain radiotherapy induces cognitive dysfunction in mice: key role of gut microbiota

Autor:	Gaofeng Zhan, Chun Yang, Xiang-Lin Yuan, Dongyu Hua, Ailin Luo, Shan Li, Xiao-Xiao Luo
Rok vydání:	2020
Předmět:	Male medicine.drug_class Antibiotics Morris water navigation task Gut flora Pathogenesis Mice 03 medical and health sciences 0302 clinical medicine medicine Animals Cognitive Dysfunction Maze Learning Pharmacology biology business.industry Probiotics Brain Cancer Cognition medicine.disease biology.organism_classification Phenotype Gastrointestinal Microbiome 030227 psychiatry Mice Inbred C57BL Prebiotics Immunology business 030217 neurology & neurosurgery Brain metastasis
Zdroj:	Psychopharmacology. 237:2089-2101
ISSN:	1432-2072 0033-3158
DOI:	10.1007/s00213-020-05520-0
Popis:	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.
Databáze:	OpenAIRE
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