Objective

Eradication of Helicobacter pylori (H. pylori) could not completely prevent the progression of gastric cancer (GC), suggesting that non-H. pylori bacteria may participate in the carcinogenesis of GC. The dysbiosis of microbiota in the stomach of GC has gradually been investigated, while the detailed mechanism that promotes GC in this process has not been elucidated. We aimed to identify a non-H. pylori bacteria that contribute to GC.

Design

GC tissues and adjacent normal tissues were collected to identify bacteria that significantly increased in GC tissues by 16S rRNA gene sequencing and fluorescence in situ hybridization (FISH) analysis. CCK8, wound healing assay, and trans-well assay were performed to analyze the tumor-promoting effect of this bacteria. Next, we detailed the mechanism for tumor-promoting effect of the bacteria by immunofluorescence, RT-qPCR, and western-blotting analysis.

Results

Comparing the microbial community from GC tissues and adjacent normal tissues, we found that Propionibacterium acnes (P. acnes) significantly increased in GC tissues, especially in H. pylori-negative tissues. We further found that the abundance of P. acnes correlated with TNM stages of GC patients. Interestingly, condition medium (CM) from P. acnes-primed macrophages promoted migration of GC cells, while P. acnes only could not. We next proved that P. acnes triggers M2 polarization of macrophages via TLR4/PI3K/Akt signaling.

Conclusions

Together, our finding identified that P. acnes could be a possible agent for the progression of GC besides H. pylori. M2 polarization of macrophages could be promoted by P. acnes via TLR4/PI3K/Akt signaling, thus triggers the progression of GC.

中文翻译：

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胃癌中过量的痤疮丙酸杆菌通过 TLR4/PI3K/Akt 信号传导促进巨噬细胞的 M2 极化

客观的

根除幽门螺杆菌（H. pylori）并不能完全阻止胃癌（GC）的进展，提示非幽门螺杆菌可能参与了胃癌的发生。GC胃中微生物群的失调已逐渐被研究，但在此过程中促进GC的详细机制尚未阐明。我们的目的是鉴定一种有助于 GC的非H. pylori细菌。

设计

收集 GC 组织和邻近的正常组织，通过 16S rRNA 基因测序和荧光原位杂交 (FISH) 分析来鉴定 GC 组织中显着增加的细菌。进行CCK8、伤口愈合试验和跨孔试验以分析该细菌的促肿瘤作用。接下来，我们通过免疫荧光、RT-qPCR 和蛋白质印迹分析详细介绍了细菌促肿瘤作用的机制。

结果

比较 GC 组织和邻近正常组织的微生物群落，我们发现 GC 组织中的痤疮丙酸杆菌( P.acnes ) 显着增加，尤其是在H. pylori阴性组织中。我们进一步发现，痤疮丙酸杆菌的丰度与 GC 患者的 TNM 分期相关。有趣的是，来自痤疮丙酸杆菌引发的巨噬细胞的条件培养基 (CM)促进了 GC 细胞的迁移，而痤疮丙酸杆菌不能。我们接下来证明了痤疮丙酸杆菌通过 TLR4/PI3K/Akt 信号传导触发巨噬细胞的 M2 极化。

结论

总之，我们的发现确定除了H. pylori之外，痤疮丙酸杆菌可能是 GC 进展的可能因素。痤疮丙酸杆菌可以通过 TLR4/PI3K/Akt 信号传导促进巨噬细胞的 M2 极化，从而触发 GC 的进展。