Genistein Reduces the Risk of Local Mammary Cancer Recurrence and Ameliorates Alterations in the Gut Microbiota in the Offspring of Obese Dams

Nutrients

Fang Liu¹  William Helferich²  MarianaPapaleo Rosim³  Caroline Dani³  Fabiade Oliveira Andrade³  Leena Hilakivi-Clarke³  Idalia Cruz³  Xiyuan Zhang³  RobertW. Li⁴  ThomasT. Y. Wang⁵ 

[1] College of Food Science and Engineering, Ocean University of China, Qingdao 266555, China;Department of Food Science and Human Nutrition, University of Illinois Urbana-Champaign, Urbana, IL 1801, USA;Department of Oncology, Georgetown University, Washington, DC 20057, USA;United States Department of Agriculture, Agricultural Research Service, Animal Genomics and Improvement Laboratory, Beltsville, MD 20705, USA;United States Department of Agriculture, Beltsville Human Nutrition Center, Diet, Genomics and Immunology Laboratory, Beltsville, MD 20705, USA;

关键词: breast cancer;    tamoxifen therapy;    antiestrogen resistance;    genistein;    gut microbiota;    tumor immune genes;   

DOI  :  10.3390/nu13010201

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown