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Sodium butyrate modulates gut microbiota and immune response in colorectal cancer liver metastatic mice

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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 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 IL-17 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.

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Fig. 1
Fig. 2

Abbreviations

NaB :

Sodium butyrate

CRC :

Colorectal cancer

CLM :

Colorectal liver metastasis

SCFAs :

Short-chain fatty acids

NK :

Natural killer

Treg :

T regulatory

Th17 :

T helper 17

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Acknowledgments

We thank Dr. Guoqi Liu for gut microbiota assays.

Funding

This work was supported by the National Natural Science Foundation of China (No. 81272493, No. 81472213), the Health Commission of Zhejiang Province (No. 2019331258, No. 2019335600), the Natural Sciences Foundation of Zhejiang Province (No. LY17H220001), and the Science Technology Department of Zhejiang Province (No. GF20H220003, No. 2015C37112).

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Author notes

  1. Ximei Ma and Zhuha Zhou contributed equally to this work.

Authors and Affiliations

  1. Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China

    Ximei Ma, Zhuha Zhou & Guanyu Wang

  2. 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

    Xujun Zhang & Hongyan Diao

  3. Central Lab of Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China

    Mengjing Fan, Yiyang Hong & Qinghua Dong

  4. Institute of Translational Medicine, School of Medicine, Zhejiang University|, Hangzhou, Zhejiang, China

    Ye Feng

  5. Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Hangzhou, Zhejiang, China

    Qinghua Dong

Authors
  1. Ximei Ma
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  2. Zhuha Zhou
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  3. Xujun Zhang
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  4. Mengjing Fan
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  5. Yiyang Hong
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  6. Ye Feng
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  7. Qinghua Dong
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  8. Hongyan Diao
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  9. Guanyu Wang
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Contributions

G. W., Q. D., and H. D. participated in the design of the study. X. M., Z. Z., Z. X., M. F., and Y. H. performed the experiments. Q. D., G. W., X. M., Z. Z., Y. F., and H. D. contributed to data interpretation and wrote the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Qinghua Dong, Hongyan Diao or Guanyu Wang.

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The authors declare that they have no competing interests.

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Ma, X., Zhou, Z., Zhang, X. et al. Sodium butyrate modulates gut microbiota and immune response in colorectal cancer liver metastatic mice. Cell Biol Toxicol 36, 509–515 (2020). https://doi.org/10.1007/s10565-020-09518-4

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  • DOI: https://doi.org/10.1007/s10565-020-09518-4

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