Probiotic strain Lactobacillus plantarum YYC-3 prevents colon cancer in mice by regulating the tumour microenvironment

Yuanchun Yue; Kai Ye; Jing Lu; Xinyu Wang; Shuwen Zhang; Liu Liu; Baoyu Yang; Khaled Nassar; Xiaoxi Xu; Xiaoyang Pang; Jiaping Lv

doi:10.1016/j.biopha.2020.110159

Probiotic strain Lactobacillus plantarum YYC-3 prevents colon cancer in mice by regulating the tumour microenvironment

Biomed Pharmacother. 2020 Jul:127:110159. doi: 10.1016/j.biopha.2020.110159. Epub 2020 Apr 27.

Authors

Yuanchun Yue¹, Kai Ye², Jing Lu³, Xinyu Wang⁴, Shuwen Zhang⁵, Liu Liu⁶, Baoyu Yang⁷, Khaled Nassar⁸, Xiaoxi Xu⁹, Xiaoyang Pang¹⁰, Jiaping Lv¹¹

Affiliations

¹ College of Food Science, Northeast Agricultural University, Harbin, 150030, PR China; Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing, 100193, PR China. Electronic address: yueyuanchungreat@163.com.
² Department of Radiology, Peking University Third Hospital, Beijing, PR China. Electronic address: yekaibysy@bjmu.edu.cn.
³ Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing, 100193, PR China. Electronic address: lujing@caas.cn.
⁴ National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, PR China. Electronic address: wangxinyu@ibp.ac.cn.
⁵ Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing, 100193, PR China. Electronic address: zhangshuwen@caas.cn.
⁶ Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing, 100193, PR China. Electronic address: liuliuwur@126.com.
⁷ College of Food Science, Northeast Agricultural University, Harbin, 150030, PR China. Electronic address: youngby2012@163.com.
⁸ Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing, 100193, PR China. Electronic address: Khalid.nassar@agr.dmu.edu.eg.
⁹ College of Food Science, Northeast Agricultural University, Harbin, 150030, PR China. Electronic address: xiaoxi_xu01@163.com.
¹⁰ Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing, 100193, PR China. Electronic address: pangxiaoyang@163.com.
¹¹ Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing, 100193, PR China. Electronic address: lvjiapingcaas@126.com.

PMID: 32353824
DOI: 10.1016/j.biopha.2020.110159

Abstract

The gut microbiota plays important roles in chronic inflammation and colon cancer. Lactobacillus is a gut-resident probiotic with benefits to host health. We recently identified Lactobacillus plantarum strain YYC-3 with strong inhibition against two colon cancer cell lines (HT-29 and Caco2). However, the inhibitory effect of YYC-3 against colon cancer in vivo has not been verified. Thus, in the present study, we explored the probiotic function of strain YYC-3 and its cell-free supernatant (YYCS) respectively in the APC^Min/+ mouse model of colon cancer during tumour development and growth, and the underlying anti-cancer mechanism. Treatment of both strain YYC-3 and the YYCS prevented the occurrence of colon tumours and mucosal damage in APC^Min/+ mice fed a high-fat diet, although YYC-3 had a stronger anti-cancer effect. The mechanism involved modulation of the immune system and downregulated expression of the inflammatory cytokines interleukin (IL)-6, IL-17 F, and IL-22, along with reduced infiltration of inflammatory cells. Moreover, YYC-3 suppressed activation of the NF-κB and Wnt signalling pathways, and restored the altered gut microbiota composition to closely match that of wild-type mice. These results lay a theoretical foundation for application of YYC-3 in colon cancer prevention.

Keywords: Colon cancer; Gut microbiota; Immune system; Lactobacillus plantarum YYC-3; Probiotic.

MeSH terms

Animals
Caco-2 Cells
Colonic Neoplasms / microbiology
Colonic Neoplasms / prevention & control*
Cytokines / metabolism
Diet, High-Fat
Disease Models, Animal
Gastrointestinal Microbiome / physiology
HT29 Cells
Humans
Lactobacillus plantarum*
Male
Mice
Mice, Inbred C57BL
NF-kappa B / metabolism
Probiotics / administration & dosage*
Probiotics / pharmacology
Tumor Microenvironment / physiology*
Wnt Signaling Pathway

Substances

Cytokines
NF-kappa B