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肠道-乳腺微生物轴是否协调癌症进展?

Does Gut-breast Microbiota Axis Orchestrates Cancer Progression?

机构信息

Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy.

Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy.

出版信息

Endocr Metab Immune Disord Drug Targets. 2022;22(11):1111-1122. doi: 10.2174/1871530322666220331145816.

Abstract

Breast cancer, even today, can cause death. Therefore, prevention and early detection are fundamental factors. The mechanisms that favour it are genetic and epigenetic, and seem to play a significant role; also, the microbiota can change estrogen levels and can induce chronic inflammation in the neoplastic site, alternating the balance between proliferation and cell death. Activated steroid hormone receptors induce transcription of genes that encode for proteins involved in cell proliferation and activate another transduction pathway, inducing cell cycle progression and cell migration. These important studies have allowed to develop therapies with selective modulators of estrogen receptors (SERMs), able to block their proliferative and pro-tumorigenic action. Of fundamental importance is also the role played by the microbiota in regulating the metabolism of estrogens and their levels in the blood. There are microbial populations that are able to promote the development of breast cancer, through the production of enzymes responsible for the deconjugation of estrogens, the increase of these in the intestine, subsequent circulation and migration to other locations, such as the udder. Other microbial populations are, instead, able to synthesize estrogen compounds or mimic estrogenic action, and interfere with the metabolism of drugs, affecting the outcome of therapies. The microbial composition of the intestine and hormonal metabolism depend largely on eating habits; the consumption of fats and proteins favours the increase of estrogen in the blood, unlike a diet rich in fiber. Therefore, in-depth knowledge of the microbiota present in the intestine-breast axis could, in the future, encourage the development of new diagnostic and therapeutic approaches to breast cancers.

摘要

即使在今天,乳腺癌也可能导致死亡。因此,预防和早期检测是至关重要的。促进乳腺癌发生的机制既有遗传的,也有表观遗传的,而且它们似乎起着重要的作用;此外,微生物组可以改变雌激素水平,并在肿瘤部位引起慢性炎症,从而改变增殖和细胞死亡之间的平衡。激活的甾体激素受体诱导参与细胞增殖的基因转录,并激活另一条转导途径,诱导细胞周期进程和细胞迁移。这些重要的研究使得能够开发出具有雌激素受体(SERMs)选择性调节剂的疗法,从而能够阻断其增殖和促肿瘤作用。微生物组在调节雌激素代谢及其在血液中的水平方面也起着至关重要的作用。有些微生物群能够通过产生负责雌激素去共轭的酶来促进乳腺癌的发展,这些酶在肠道中增加,随后在肠道中循环并迁移到其他部位,如乳房。其他微生物群则能够合成雌激素化合物或模拟雌激素作用,并干扰药物代谢,从而影响治疗效果。肠道和激素代谢的微生物组成在很大程度上取决于饮食习惯;脂肪和蛋白质的摄入会增加血液中的雌激素水平,而富含纤维的饮食则不然。因此,深入了解肠道-乳房轴中存在的微生物群,未来可能会鼓励开发新的乳腺癌诊断和治疗方法。

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