Sodium butyrate modulates gut microbiota and immune response in colorectal cancer liver metastatic mice
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Sodium butyrate modulates gut microbiota and immune response in colorectal cancer liver metastatic mice Ximei Ma & Zhuha Zhou & Xujun Zhang & Mengjing Fan & Yiyang Hong & Ye Feng & Qinghua Dong & Hongyan Diao & Guanyu Wang
Received: 23 December 2019 / Accepted: 18 February 2020 # Springer Nature B.V. 2020
Abstract Colorectal cancer (CRC) liver metastasis (CLM) is the leading death cause of CRC patients, but there is no satisfied approach to treat CLM. Gut microbiota plays a pivotal role in CRC initiation and
Ximei Ma and Zhuha Zhou contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10565-020-09518-4) contains supplementary material, which is available to authorized users. X. Ma : Z. Zhou : G. Wang (*) Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China e-mail: [email protected] X. Zhang : H. Diao (*) State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China e-mail: [email protected] M. Fan : Y. Hong : Q. Dong Central Lab of Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China Y. Feng Institute of Translational Medicine, School of Medicine, Zhejiang University|, Hangzhou, Zhejiang, China Q. Dong (*) Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Hangzhou, Zhejiang, China e-mail: [email protected]
development. Targeting dysbiosis of the gut microbiota might open up new opportunities for CLM treatment. Here, we investigated the efficacy of sodium butyrate (NaB), a major product of gut microbial fermentation, in modulating gut microbiota in CLM mice. NaB supplement decreased mouse colon cancer CT26 cell liver metastasis in intrasplenic tumor injection model of BALB/c mice. Using 16S rRNA gene sequencing, we found altered microbiota composition in CLM mice, characterized by increases of Firmicutes and Proteobacteria. NaB beneficially changed dysbiosis in CLM mice. Functional analysis of the KEGG pathways showed that NaB changed pathways related to immune system diseases and primary immunodeficiency in CLM mice. In addition, NaB decreased T regulatory cells and increased natural killer T cells and T helper 17 cells, accordingly decreased IL-10 and increased IL17 secretion in CLM mice liver. In conclusion, NaB beneficially modulated gut microbiota and improved host immune response in CLM mice. These findings demonstrate the therapeutic potential of NaB in CLM treatment. Keywords Sodium butyrate . Colorectal cancer . Liver metastasis . Gut microbiota . Immunity Abbreviations NaB Sodium butyrate CRC Colorectal cancer CLM Colorectal liver metastasis SCFAs Short-chain fatty acids NK Natural killer
Cell Biol Toxicol
Cell Biol Toxicol
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