Bile acid metabolism dysregulation associates with cancer cachexia: roles of liver and gut microbiome

Autor: Lixing Feng, Wanli Zhang, Qiang Shen, Chunxiao Miao, Lijuan Chen, Yiwei Li, Xiaofan Gu, Meng Fan, Yushui Ma, Hui Wang, Xuan Liu, Xiongwen Zhang
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Journal of Cachexia, Sarcopenia and Muscle, Vol 12, Iss 6, Pp 1553-1569 (2021)
Druh dokumentu: article
ISSN: 2190-6009
2190-5991
DOI: 10.1002/jcsm.12798
Popis: Abstract Background Cancer cachexia is a multifactorial metabolic syndrome in which bile acid (BA) metabolism might be involved. The aim of the present study was to clarify the contribution of liver and gut microbiota to BA metabolism disturbance in cancer cachexia and to check the possibility of targeting BA metabolism using agents such as tauroursodeoxycholic acid (TUDCA) for cancer cachexia therapy. Methods The BA profiles in liver, intestine, and serum of mice with cancer cachexia induced by inoculation of colon C26 tumour cells were analysed using metabolomics methods and compared with that of control mice. Proteomic analysis of liver protein expression profile and 16S rRNA gene sequencing analysis of gut microbiota composition in cancer cachexia mice were conducted. Expression levels of genes related to farnesoid X receptor (FXR) signalling pathway in the intestine and liver tissues were analysed using RT–PCR analysis. The BA profiles in serum of clinical colon cancer patients with or without cachexia were also analysed and compared with that of healthy volunteers. The effects of TUDCA in treating cancer cachexia mice were observed. Results In the liver of cancer cachexia mice, expression of BA synthesis enzymes was inhibited while the amount of total BAs increased (P
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