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PNAS:肠道益生菌可抑制肝癌生长

 HCC(HepatocellularCarcinoma)是肝癌中最为常见的一种,致死率高。它是一种高度血管化的肿瘤,通常与T辅助细胞17(Th17)和促炎性血管生成因子IL-17(由Th17分泌)有关。研究发现在肿瘤接种前用一种新型益生菌制剂(命名为Prohep)喂食小鼠一周后,相比于对照组,小鼠的肿瘤重量和体积减少了40%。这是因为Prohep可下调Th17和IL-17,阻止炎症和血管生成,限制了肿瘤生长。

参阅文献:

Probiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice.

Proc Natl Acad Sci U S A. 2016 Mar 1;113(9):E1306-15. doi: 10.1073/pnas.1518189113. 
The beneficial roles of probiotics in lowering the gastrointestinal inflammation and preventing colorectal cancer have been frequently demonstrated, but their immunomodulatory effects and mechanism in suppressing the growth of extraintestinal tumors remain unexplored. Here, we adopted a mouse model and metagenome sequencing to investigate the efficacy of probiotic feeding in controlling s.c. hepatocellular carcinoma (HCC) and the underlying mechanism suppressing the tumor progression. Our result demonstrated that Prohep, a novel probiotic mixture, slows down the tumor growth significantly and reduces the tumor size and weight by 40% compared with the control. From a mechanistic point of view the down-regulated IL-17 cytokine and its major producer Th17 cells, whose levels decreased drastically, played critical roles in tumor reduction upon probiotics feeding. Cell staining illustrated that the reduced Th17 cells in the tumor of the probiotic-treated group is mainly caused by the reduced frequency of migratory Th17 cells from the intestine and peripheral blood. In addition, shotgun-metagenome sequencing revealed the crosstalk between gut microbial metabolites and the HCC development. Probiotics shifted the gut microbial community toward certain beneficial bacteria, including Prevotella and Oscillibacter, that are known producers of antiinflammatory metabolites, which subsequently reduced the Th17 polarization and promoted the differentiation of antiinflammatory Treg/Tr1 cells in the gut. Overall, our study offers novel insights into the mechanism by which probiotic treatment modulates the microbiota and influences the regulation of the T-cell differentiation in the gut, which in turn alters the level of the proinflammatory cytokines in the extraintestinal tumor microenvironment.
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