Genistein Reduces the Risk of Local Mammary Cancer Recurrence and Ameliorates Alterations in the Gut Microbiota in the Offspring of Obese Dams.
Genistein Reduces the Risk of Local Mammary Cancer Recurrence and Ameliorates Alterations in the Gut Microbiota in the Offspring of Obese Dams.
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DOI：
10.3390/nu13010201
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发表时间：
2021-01-11
期刊：
影响因子：
5.9
通讯作者：
Hilakivi-Clarke L
中科院分区：
文献类型：
--
作者：
Andrade FO;Liu F;Zhang X;Rosim MP;Dani C;Cruz I;Wang TTY;Helferich W;Li RW;Hilakivi-Clarke L
雌激素受体阳性乳腺癌的复发风险保持不变，即使在诊断后 20 年也是如此。在子宫内就已预先编程的患者中，例如肥胖母亲所生的女儿，复发的可能性更大。母亲肥胖持续改变后代的肠道微生物群并损害肿瘤免疫反应。为了研究肠道菌群失调是否与肥胖大鼠后代乳腺癌复发的风险增加有关，我们给成年后代喂食染料木黄酮，已知它对肠道细菌有有益作用。然而，金雀异黄素对乳腺癌的作用仍存在争议。我们发现，他莫昔芬反应后摄入金雀异黄酮可以防止肥胖母鼠后代局部复发风险增加，但对对照后代没有影响。在肥胖母鼠的后代中观察到炎症性普雷沃氏菌科和肠杆菌科的丰度显着增加，而产生短链脂肪酸的梭菌科的数量显着减少。补充金雀异黄素逆转了这些变化，并逆转了肠道代谢物 N-乙酰缬氨酸水平的升高，而肠道代谢物 N-乙酰缬氨酸水平与全因死亡率增加有关。补充金雀异黄素还可以降低遗传毒性酪胺水平，增加代谢物，改善炎症的前消退阶段，并逆转肥胖母鼠后代中多种免疫抑制基因升高的肿瘤 mRNA 表达。如果适用于乳腺癌患者，预防乳腺癌复发的尝试可能需要重点关注有益于改变肠道微生物群的饮食改变。
The risk of recurrence of estrogen receptor-positive breast cancer remains constant, even 20 years after diagnosis. Recurrence may be more likely in patients pre-programmed for it already in the womb, such as in the daughters born to obese mothers. Maternal obesity persistently alters offspring’s gut microbiota and impairs tumor immune responses. To investigate if the gut dysbiosis is linked to increased risk of mammary cancer recurrence in the offspring of obese rat dams, we fed adult offspring genistein which is known to have beneficial effects on the gut bacteria. However, the effects of genistein on breast cancer remain controversial. We found that genistein intake after tamoxifen response prevented the increased risk of local recurrence in the offspring of obese dams but had no effect on the control offspring. A significant increase in the abundance of inflammatory Prevotellaceae and Enterobacteriaceae, and a reduction in short-chain fatty acid producing Clostridiaceae was observed in the offspring of obese dams. Genistein supplementation reversed these changes as well as reversed increased gut metabolite N-acetylvaline levels which are linked to increased all-cause mortality. Genistein supplementation also reduced genotoxic tyramine levels, increased metabolites improving pro-resolving phase of inflammation, and reversed the elevated tumor mRNA expression of multiple immunosuppressive genes in the offspring of obese dams. If translatable to breast cancer patients, attempts to prevent breast cancer recurrences might need to focus on dietary modifications which beneficially modify the gut microbiota.
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影响因子：
48
作者：
Huan T;Forsberg EM;Rinehart D;Johnson CH;Ivanisevic J;Benton HP;Fang M;Aisporna A;Hilmers B;Poole FL;Thorgersen MP;Adams MWW;Krantz G;Fields MW;Robbins PD;Niedernhofer LJ;Ideker T;Majumder EL;Wall JD;Rattray NJW;Goodacre R;Lairson LL;Siuzdak G
通讯作者：
Siuzdak G
影响因子：
4.2
作者：
Allred, Kimberly F.;Yackley, Katarina M.;Allred, Clinton D.
通讯作者：
Allred, Clinton D.
影响因子：
6.4
作者：
de Assis, Sonia;Khan, Galam;Hilakivi-Clarke, Leena
通讯作者：
Hilakivi-Clarke, Leena
影响因子：
9.2
作者：
Al-Akwaa, Fadhl M.;Yunits, Breck;Garmire, Lana X.
通讯作者：
Garmire, Lana X.
影响因子：
15.5
作者：
Fernandes AD;Reid JN;Macklaim JM;McMurrough TA;Edgell DR;Gloor GB
通讯作者：
Gloor GB