Nutritional combinatorial impact on the gut microbiota and plasma short-chain fatty acids levels in the prevention of mammary cancer in Her2/neu estrogen receptor-negative transgenic mice

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.

The breast tissue microbiome, stroma, immune cells and breast cancer

“…Genistein has tumor inhibitory properties in vivo, although it's role in breast tissue is unstudied [38] . In animal studies, dietary modulation affects Adlercreutzia abundance in the stool where it may serve as a biomarker of the efficacy of anti-cancer dietary supplements [39] . Adlercreutzia abundance in the gut microbiome was positively correlated with BMI and inflammation as measured by serum leptin and adipsin concentrations in one study of obese patients [40] .…”

Probiotics and their beneficial effects on alcohol-induced liver injury in a rat model: the role of fecal microbiota

“…Additional analyses from our study demonstrated that Allobaculum was negatively correlated with the levels of ALT, AST, TNF-α, and MDA suggesting that Allobaculum may be protective against inflammation and oxidative stress. The increase in relative abundance of Allobaculum in both treatment groups might explain the anti-inflammatory effect of probiotics, possibly through the action of short-chain fatty acids produced by Allobaculum [ 32 ]. Moreover, the increased abundance of Bifidobacterium , which has previously been shown to improve intestinal integrity [ 33 ], might explain the reduction of serum endotoxin and TLR-4 expression in probiotics-treated rats.…”

Green Tea and Its Relation to Human Gut Microbiome

“…Sharma et al [ 51 ] investigated the protective effect of green tea polyphenols, broccoli sprouts, and both together in the development of mammary cancer. For that purpose, the researchers used Her2/neu transgenic spontaneous ER(-) mammary cancer mouse models.…”