31Breast cancer is the second leading cause of cancer-related mortality in women. Various 32 nutritional compounds possess anti-carcinogenic properties which may be mediated through their 4 75 an isothiocyanate present in cruciferous vegetables such as BSp, kale, bok choy, cauliflower and 76 cabbage and also has chemopreventive/chemotherapeutic effects against numerous types of 77 cancers via epigenetic mechanisms [11][12][13]. Studies have shown that SFN is a potent inhibitor of 78 histone deacetylase (HDAC), which is an enzyme that modulates epigenetic machinery by removal 79 of an acetyl group from histone residues. Studies have shown that SFN induced G1/S arrest, led to 80 down-regulation of SEI-1 and cyclin D2, increased levels of p21 and p27 and promoted cellular 81 senescence in breast cancer [14, 15]. (-)-Epigallocatechin-3-gallate (EGCG), a major polyphenol 82 in green tea, induces epigenetic modulations such as inhibition of DNA methytransferases 83 (DNMTs) and has numerous anticarcinogenic properties both in vitro and in vivo against several 84 cancers including breast cancer [16-20]. The anti-tumor mechanisms of GTPs and EGCG involve 85 induction of cell-cycle arrest, mitochondrial-mediated apoptosis, inhibition of IL-6 and induction 86 of tumor necrosis factor-α expression, inhibition of enzymes that regulate the glycolytic process 87 and repression of glucose metabolism [6, 21-23]. 88 Our previous studies have shown that the combination of BSp and GTPs resulted in 89 synergistic inhibition of cellular proliferation, ERα reactivation via regulation of DNMT1 and 90 HDAC1 expression in the ERα (-) breast cancer cell lines MDA-MB-231 and MDA-MB-157, and 91 also resulted in a significant inhibition of tumor development in an ER (-) xenograft mouse model 92 [24]. Additionally, these combined dietary components induced cellular apoptosis and cell cycle 93 arrest in the transformed breast cancer SHR cells (normal human mammary epithelial cells 94 transfected with SV40, hTERT and H-Ras genes), and led to genome-wide epigenetic alterations. 95 This combination treatment administered in a breast cancer xenograft mouse model also resulted 96 in significant inhibition of tumor growth when compared with singly administrated compounds 97 [25]. In addition, our recent study reported that the prenatal or maternal consumption of BSp has 5 98 more protective effects on tumor development than postnatal or adulthood administration of BSp 99 in SV40 transgenic and Her2/neu transgenic mouse models [26]. 100 The human gastrointestinal tract harbors trillions of microorganisms (≥10 14 ) that are 101 reported to be at an approximate ratio of 1:1 with the human cells [27]. The gut microbiota plays 102 an important role in regulation of human metabolic and physiological functions by production of 103 crucial metabolites such as short chain fatty acids (SCFAs) [28, 29]. SCFAs are produced from 104 the fermentation of non-digestible carbohydrates by gut microbiota and the major SCFAs include 105 butyrate, acetate and propionate ...