Abstract
Breast cancer is the second leading cause of cancer-related mortality in women. Various nutritional compounds possess anti-carcinogenic properties which may be mediated through their effects on the gut microbiota and its production of short-chain fatty acids (SCFAs) for the prevention of breast cancer. We evaluated the impact of broccoli sprouts (BSp), green tea polyphenols (GTPs) and their combination on the gut microbiota and SCFAs metabolism from the microbiota in Her2/neu transgenic mice that spontaneously develop estrogen receptor-negative [ER(-)] mammary tumors. The mice were grouped based on the dietary treatment: control, BSp, GTPs or their combination from beginning in early life (BE) or life-long from conception (LC). We found that the combination group showed the strongest inhibiting effect on tumor growth volume and a significant increase in tumor latency. BSp treatment was integrally more efficacious than the GTPs group when compared to the control group. There was similar clustering of microbiota of BSp-fed mice with combination-fed mice, and GTPs-fed mice with control-fed mice at pre-tumor in the BE group and at pre-tumor and post-tumor in the LC group. The mice on all dietary treatment groups incurred a significant increase of Adlercreutzia, Lactobacillus genus and Lachnospiraceae, S24-7 family in the both BE and LC groups. We found no change in SCFAs levels in the plasma of BSp-fed, GTPs-fed and combination-fed mice of the BE group. Marked changes were observed in the mice of the LC group consisting of significant increases in propionate and isobutyrate in GTPs-fed and combination-fed mice. These studies indicate that nutrients such as BSp and GTPs differentially affect the gut microbial composition in both the BE and LC groups and the key metabolites (SCFAs) levels in the LC group. The findings also suggest that temporal factors related to different time windows of consumption during the life-span can have a promising influence on the gut microbial composition, SCFAs profiles and ER(-) breast cancer prevention.
Highlights
Breast cancer is a significant health concern worldwide as it is the second most common cause of cancer-related mortality among women
The current study highlights the impact of broccoli sprouts (BSp), green tea polyphenols (GTPs) and combination diet on the gut microbiome and Short-chain fatty acid (SCFA) levels of Her2/neu transgenic mice at two specific time periods, which may help reveal a potential mechanism by which diet can regulate breast carcinogenesis
Overall our results demonstrated that combination dietary treatment showed the strongest delaying effect on tumor volume and led to a significant increase in tumor latency and the BSp diet group was integrally more efficacious than the GTPs group when compared to control treatments in both the beginning in early life (BE) and long from conception (LC) groups
Summary
Breast cancer is a significant health concern worldwide as it is the second most common cause of cancer-related mortality among women. Triple-negative breast cancer (TNBC) patients have a poor prognosis and fewer cancer prevention and treatment options due to lack of target-directed approaches and the aggressive nature of this disease [7]. The commonly employed treatment approaches for TNBC patients and metastatic breast cancer patients are surgical, chemotherapy, radiation therapy, and palliative therapy [8]. These procedures have an array of short-term or long-term side effects in the patients such as loss of hair, vomiting, skin disorders, fatigue, nausea, anemia, diarrhea, muscle disorder, and nerve diseases [8, 9]. There is a need for effective and safe approaches for prevention and treatment of TNBC
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