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.
Mol Nutr Food Res. 2021 Aug;65(15):e2100096. doi: 10.1002/mnfr.202100096. Epub 2021 Jun 18.
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.
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.
The results provide new information on the role and mechanisms of action of probiotics in attenuating extra-intestinal tumor metastasis.
益生菌可减少胃肠道炎症和预防结直肠癌，其有益效果已被报道，但益生菌在抑制肠道外肿瘤进展中的免疫调节作用的机制仍不清楚。
本研究表明，益生菌补充剂可减轻小鼠黑色素瘤细胞的肺转移。用 VSL#3 益生菌喂养小鼠会改变肠道微生物群的组成和比例。肠道细菌组成的变化，如lachnospiraceae、链球菌和lachnoclostridium 的丰度，与肠道内短链脂肪酸的产生有关。喂食 VSL#3 后，肠道和血液中的丙酸和丁酸浓度升高，丙酸和丁酸水平的升高促进了趋化因子（C-C 基序）配体 20（CCL20）在肺内皮细胞中的表达，并通过 CCL20/趋化因子受体 6 轴将 Th17 细胞募集到肺部。Th17 细胞的募集减少了肺部肿瘤灶的数量，并减轻了小鼠黑色素瘤细胞的肺转移。
这些结果为益生菌在减轻肠道外肿瘤转移中的作用和作用机制提供了新的信息。
