Laborda-Illanes Aurora, Sánchez-Alcoholado Lidia, Boutriq Soukaina, Plaza-Andrades Isaac, Peralta-Linero Jesús, Alba Emilio, González-González Alicia, Queipo-Ortuño María Isabel
Unidad de Gestión Clínica Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA)-CIMES-UMA, 29010 Málaga, Spain.
Facultad de Medicina, Universidad de Málaga, 29071 Málaga, Spain.
Cancers (Basel). 2021 Jun 23;13(13):3141. doi: 10.3390/cancers13133141.
In this review we summarize a possible connection between gut microbiota, melatonin production, and breast cancer. An imbalance in gut bacterial population composition (dysbiosis), or changes in the production of melatonin (circadian disruption) alters estrogen levels. On the one hand, this may be due to the bacterial composition of estrobolome, since bacteria with β-glucuronidase activity favour estrogens in a deconjugated state, which may ultimately lead to pathologies, including breast cancer. On the other hand, it has been shown that these changes in intestinal microbiota stimulate the kynurenine pathway, moving tryptophan away from the melatonergic pathway, thereby reducing circulating melatonin levels. Due to the fact that melatonin has antiestrogenic properties, it affects active and inactive estrogen levels. These changes increase the risk of developing breast cancer. Additionally, melatonin stimulates the differentiation of preadipocytes into adipocytes, which have low estrogen levels due to the fact that adipocytes do not express aromatase. Consequently, melatonin also reduces the risk of breast cancer. However, more studies are needed to determine the relationship between microbiota, melatonin, and breast cancer, in addition to clinical trials to confirm the sensitizing effects of melatonin to chemotherapy and radiotherapy, and its ability to ameliorate or prevent the side effects of these therapies.
在本综述中，我们总结了肠道微生物群、褪黑素生成与乳腺癌之间可能存在的联系。肠道细菌种群组成失衡（生态失调）或褪黑素生成变化（昼夜节律紊乱）会改变雌激素水平。一方面，这可能归因于雌激素代谢菌的细菌组成，因为具有β-葡萄糖醛酸酶活性的细菌有利于雌激素处于去结合状态，这最终可能导致包括乳腺癌在内的疾病。另一方面，研究表明肠道微生物群的这些变化会刺激犬尿氨酸途径，使色氨酸从褪黑素能途径分流，从而降低循环中的褪黑素水平。由于褪黑素具有抗雌激素特性，它会影响活性和非活性雌激素水平。这些变化增加了患乳腺癌的风险。此外，褪黑素会刺激前脂肪细胞分化为脂肪细胞，由于脂肪细胞不表达芳香化酶，其雌激素水平较低。因此，褪黑素也会降低患乳腺癌的风险。然而，除了进行临床试验以证实褪黑素对化疗和放疗的增敏作用及其改善或预防这些疗法副作用的能力外，还需要更多研究来确定微生物群、褪黑素与乳腺癌之间的关系。
