Genistein Reduces the Risk of Local Mammary Cancer Recurrence and Ameliorates Alterations in the Gut Microbiota in the Offspring of Obese Dams
| Autor: | Fábia de Oliveira Andrade, Fang Liu, Thomas T.Y. Wang, Caroline Dani, Robert W. Li, Leena Hilakivi-Clarke, Mariana Papaleo Rosim, Xiyuan Zhang, William G. Helferich, Idalia Cruz |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
medicine.drug_class Offspring Genistein Physiology Inflammation Mammary Neoplasms Animal lcsh:TX341-641 Gut flora tumor immune genes Article Rats Sprague-Dawley genistein 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Breast cancer Immune system breast cancer Pregnancy medicine Animals antiestrogen resistance Obesity Nutrition and Dietetics biology gut microbiota business.industry medicine.disease biology.organism_classification tamoxifen therapy Gastrointestinal Microbiome Rats 030104 developmental biology chemistry Estrogen 030220 oncology & carcinogenesis Prenatal Exposure Delayed Effects Female medicine.symptom business lcsh:Nutrition. Foods and food supply Tamoxifen Food Science medicine.drug |
| Zdroj: | Nutrients, Vol 13, Iss 201, p 201 (2021) Nutrients Volume 13 Issue 1 |
| ISSN: | 2072-6643 |
| Popis: | 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&rsquo 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. |
| Databáze: | OpenAIRE |
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