Maternal obesity and resistance to breast cancer treatments among offspring: Link to gut dysbiosis.
Maternal obesity and resistance to breast cancer treatments among offspring: Link to gut dysbiosis.
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DOI：
10.1002/cnr2.1752
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发表时间：
2022-12
期刊：
影响因子：
1.7
通讯作者：
Hilakivi-Clarke, Leena
中科院分区：
文献类型：
--
作者：
Andrade, Fabia de Oliveira;Verma, Vivek;Hilakivi-Clarke, Leena
在美国，大约有5万例新的癌症病例是由肥胖引起的。肥胖对乳腺癌的不利影响在影响早期发展时可能最为深刻；也就是说，在一个肥胖孕妇的子宫里。母亲肥胖对后代有几个长期的不良健康影响，包括增加后代患乳腺癌的风险和死亡率。肠道微生物群是肥胖的一个参与者，也可能影响乳腺癌的发生。肠道菌群是在生命早期建立的，婴儿肠道的微生物组成由于母亲肥胖而永久失调。来自微生物群的代谢物，特别是短链脂肪酸（SCFAs），在介导肠道细菌对多种生物功能的影响中起着关键作用，如免疫系统，包括肿瘤免疫反应。母亲肥胖可以预先规划女儿的乳腺癌更具侵袭性，对治疗反应较差，因此更有可能导致乳腺癌相关死亡。母体肥胖还可能通过炎症相关微生物群丰度的增加和与scfa产生相关的细菌丰度的减少，诱导对免疫检查点抑制剂（ICB）治疗的不良反应。饮食干预增加产生SCFAs的细菌的丰度可能会逆转后代对乳腺癌治疗的抵抗力。由于免疫疗法已成为许多癌症的高效治疗方法，尽管迫切需要扩大对这些治疗有反应的患者人数。可能导致ICB难治性的因素之一可能是母亲肥胖，这是基于其对后代ICB治疗反应的微生物标记物的影响。由于在西方社会，大约40%的儿童是由肥胖母亲所生，因此确定母亲肥胖是否会损害后代对癌症免疫疗法的反应是很重要的。
About 50 000 new cases of cancer in the United States are attributed to obesity. The adverse effects of obesity on breast cancer may be most profound when affecting the early development; that is, in the womb of a pregnant obese mother. Maternal obesity has several long‐lasting adverse health effects on the offspring, including increasing offspring's breast cancer risk and mortality. Gut microbiota is a player in obesity as well as may impact breast carcinogenesis. Gut microbiota is established early in life and the microbial composition of an infant's gut becomes permanently dysregulated because of maternal obesity. Metabolites from the microbiota, especially short chain fatty acids (SCFAs), play a critical role in mediating the effect of gut bacteria on multiple biological functions, such as immune system, including tumor immune responses. Maternal obesity can pre‐program daughter's breast cancer to be more aggressive, less responsive to treatments and consequently more likely to cause breast cancer related death. Maternal obesity may also induce poor response to immune checkpoint inhibitor (ICB) therapy through increased abundance of inflammation associated microbiome and decreased abundance of bacteria that are linked to production of SCFAs. Dietary interventions that increase the abundance of bacteria producing SCFAs potentially reverses offspring's resistance to breast cancer therapy. Since immunotherapies have emerged as highly effective treatments for many cancers, albeit there is an urgent need to enlarge the patient population who will be responsive to these treatments. One of the factors which may cause ICB refractoriness could be maternal obesity, based on its effects on the microbiota markers of ICB therapy response among the offspring. Since about 40% of children are born to obese mothers in the Western societies, it is important to determine if maternal obesity impairs offspring's response to cancer immunotherapies.
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影响因子：
5.9
作者：
Andrade FO;Liu F;Zhang X;Rosim MP;Dani C;Cruz I;Wang TTY;Helferich W;Li RW;Hilakivi-Clarke L
通讯作者：
Hilakivi-Clarke L
DOI：
10.3322/caac.21398
发表时间：
2017-07-08
期刊：
CA: a cancer journal for clinicians
影响因子：
--
作者：
Bhatt AP;Redinbo MR;Bultman SJ
通讯作者：
Bultman SJ
影响因子：
7.3
作者：
Ang Z;Ding JL
通讯作者：
Ding JL
影响因子：
3.4
作者：
Cerdo, Tomas;Ruiz, Alicia;Campoy, Cristina
通讯作者：
Campoy, Cristina
影响因子：
4
作者：
Cani, Patrice D.
通讯作者：
Cani, Patrice D.