Department of Medical Oncology and Laboratory of Molecular Targeted Therapy in Oncology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, 610041, PR China.
Southwest medical university, Luzhou, Sichuan Province, 646000, PR China.
BMC Microbiol. 2020 Apr 9;20(1):82. doi: 10.1186/s12866-020-01739-1.
The aim was to evaluate the changes of 16S rDNA sequencing and LC-MS metabolomics in breast cancer and explore the growth inhibition of breast cancer cells by Faecalibacterium prausnitzii.
Total 49 significantly different flora and 26 different metabolites were screened between two groups, and the correlation was calculated. Relative abudance of Firmicutes and Bacteroidetes were decreased, while relative abundance of verrucomicrobla, proteobacteria and actinobacteria was increased in breast cancer group. Differentially expressed metabolites were mainly enriched in pathways such as linoleic acid metabolism, retrograde endocannabinoid signaling, biosynthesis of unsaturated fatty acids, choline metabolism in cancer and arachidonic acid metabolism. Lipid upregulation was found in breast cancer patients, especially phosphorocholine. The abundance of Faecalibacterium was reduced in breast cancer patients, which was negatively correlated with various phosphorylcholines. Moreover, Faecalibacterium prausnitzii, the most well-known species in Faecalibacterium genus, could inhibit the secretion of interleukin-6 (IL-6) and the phosphorylation of Janus kinases 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) in breast cancer cells. Faecalibacterium prausnitzii also suppressed the proliferation and invasion and promoted the apoptosis of breast cancer cells, while these effects disappeared after adding recombinant human IL-6.
Flora-metabolites combined with the flora-bacteria (such as Faecalibacterium combined with phosphorocholine) might a new detection method for breast cancer. Faecalibacterium may be helpful for prevention of breast cancer. Faecalibacterium prausnitzii suppresses the growth of breast cancer cells through inhibition of IL-6/STAT3 pathway.
本研究旨在评估 16S rDNA 测序和 LC-MS 代谢组学在乳腺癌中的变化,并探索普拉梭菌对乳腺癌细胞生长的抑制作用。
两组间共筛选出 49 种差异菌群和 26 种差异代谢物,并计算了它们的相关性。乳腺癌组厚壁菌门和拟杆菌门的相对丰度降低,疣微菌门、变形菌门和放线菌门的相对丰度增加。差异表达的代谢物主要富集在亚麻酸代谢、逆行内源性大麻素信号转导、不饱和脂肪酸的生物合成、癌症中的胆碱代谢和花生四烯酸代谢等通路中。乳腺癌患者中发现脂质上调,特别是磷酸胆碱。乳腺癌患者中普拉梭菌的丰度降低,且与各种磷酸胆碱呈负相关。此外,普拉梭菌属中最著名的物种普拉梭菌可抑制乳腺癌细胞中白细胞介素-6(IL-6)的分泌和 Janus 激酶 2(JAK2)/信号转导和转录激活因子 3(STAT3)的磷酸化。普拉梭菌还抑制乳腺癌细胞的增殖、侵袭,促进其凋亡,而添加重组人白细胞介素-6 后这些作用消失。
菌群-代谢物联合菌群-细菌(如普拉梭菌与磷酸胆碱)可能成为乳腺癌的一种新的检测方法。普拉梭菌可能有助于预防乳腺癌。普拉梭菌通过抑制 IL-6/STAT3 通路抑制乳腺癌细胞的生长。