Alter between gut bacteria and blood metabolites and the anti-tumor effects of Faecalibacterium prausnitzii in breast cancer

Alter between gut bacteria and blood metabolites and the anti-tumor effects of Faecalibacterium prausnitzii in breast cancer
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DOI:
10.1186/s12866-020-01739-1
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发表时间:
2020-04-09
期刊:
影响因子:
4.2
通讯作者:
Wang, Xin
Wang, Xin
中科院分区:
生物学3区
文献类型:
--
作者:
Ma, Ji;Sun, Lingqi;Wang, Xin

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背景研究普氏粪杆菌对乳腺癌细胞的16 S rDNA序列分析和LC-MS代谢组学的影响,探讨普氏粪杆菌对乳腺癌细胞的生长抑制作用。结果共筛选出49种差异显著的植物群和26种代谢产物,并计算出相关性。乳腺癌组厚壁菌门和拟杆菌门相对丰度降低,疣状微生物门、变形菌门和放线菌门相对丰度升高。差异表达的代谢产物主要富集在亚油酸代谢、内源性大麻素信号传导、不饱和脂肪酸生物合成、肿瘤胆碱代谢和花生四烯酸代谢等途径中。在乳腺癌患者中发现脂质上调,尤其是磷酸胆碱。乳腺癌患者粪杆菌丰度降低,与各种磷酸胆碱呈负相关。此外,普氏粪杆菌(Faecalibacterium prausnitzii)作为粪杆菌属中最知名的菌种,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(JAK 2)/信号转导和转录激活因子3(STAT 3)的磷酸化。普氏粪杆菌还抑制乳腺癌细胞的增殖和侵袭,促进细胞凋亡,而加入重组人IL-6后,这些作用消失。结论菌群代谢产物结合菌群(如粪杆菌结合磷酸胆碱)可能成为乳腺癌的一种新的检测方法。粪杆菌可能有助于预防乳腺癌。普氏粪杆菌通过抑制IL-6/STAT 3通路抑制乳腺癌细胞的生长。
Background 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. Results 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. Conclusions 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.