Lili Chen1, Xinyu Zhou1, Yawei Wang1, Dake Wang1, Yueshuang Ke1, Xianlu Zeng1. 1. The Key Laboratory of Molecular Epigenetics of Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University, 5268 Renmin Street, Changchun, Jilin, 130024, China.
Abstract
SCOPE: The beneficial effects of probiotics in reducing gastrointestinal inflammation and in preventing colorectal cancer have been reported, but the mechanism underlying the immunomodulatory effect of probiotics in inhibiting extra-intestinal tumor progression remains unclear. METHODS AND RESULTS: This study shows that probiotic supplementation attenuate lung metastasis of melanoma cells in mice. Feeding mice with VSL#3 probiotics change the composition and proportion of gut microbiota. The changes in gut bacteria composition, such as in the abundance of Lachnospiraceae, Streptococcus, and Lachnoclostridium, are associated with the production of short-chain fatty acids in the gut. The concentrations of propionate and butyrate are upregulated in gut and blood after feeding VSL#3, and the increase in propionate and butyrate levels promotes the expression of chemokine (C-C motif) ligand 20 (CCL20) in lung endothelial cells and the recruitment of T helper 17 (Th17) cells to the lungs via the CCL20/chemokine receptor 6 axis. The recruitment of Th17 cells decreases the number of tumor foci in lungs and attenuates the lung metastasis of melanoma cells in mice. CONCLUSIONS: The results provide new information on the role and mechanisms of action of probiotics in attenuating extra-intestinal tumor metastasis.
SCOPE: The beneficial effects of probiotics in reducing gastrointestinal inflammation and in preventing colorectal cancer have been reported, but the mechanism underlying the immunomodulatory effect of probiotics in inhibiting extra-intestinal tumor progression remains unclear. METHODS AND RESULTS: This study shows that probiotic supplementation attenuate lung metastasis of melanoma cells in mice. Feeding mice with VSL#3 probiotics change the composition and proportion of gut microbiota. The changes in gut bacteria composition, such as in the abundance of Lachnospiraceae, Streptococcus, and Lachnoclostridium, are associated with the production of short-chain fatty acids in the gut. The concentrations of propionate and butyrate are upregulated in gut and blood after feeding VSL#3, and the increase in propionate and butyrate levels promotes the expression of chemokine (C-C motif) ligand 20 (CCL20) in lung endothelial cells and the recruitment of T helper 17 (Th17) cells to the lungs via the CCL20/chemokine receptor 6 axis. The recruitment of Th17 cells decreases the number of tumor foci in lungs and attenuates the lung metastasis of melanoma cells in mice. CONCLUSIONS: The results provide new information on the role and mechanisms of action of probiotics in attenuating extra-intestinal tumor metastasis.
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