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Page 26 of 36 Dave et al. J Cancer Metastasis Treat 2020;6:46 I http://dx.doi.org/10.20517/2394-4722.2020.106

Figure 13. The figure shows a Venn diagram where each circle represents one group of microorganisms. The values in overlapping parts
®
represent common Operational Taxonomic Units (OTUs) while others are OTUs specific to each group. Female HSD: ICR (CD-1 ) mice
at the age of 4 weeks were divided into four groups and given the following diets ad libitum for 20 weeks: S1.0D, standard synthetic diet,
S2.0D; standard diet supplemented with 5% whole grape powder; S4.0D, high-fat (Western) diet;S5.0D, high-fat diet supplemented
with 5% whole grape powder. The gut microbiota was analyzed using fecal samples. The data illustrate dietary grape supplementation
influenced the composition of the gut microbiome. The overall organization of the gut microbiome is altered by grape and a higher
number of microbiome groups can be observed in the grape fed diet groups

example, recent studies have demonstrated the neuroprotective potential of phytochemicals by reducing
chemotherapy-induced CRCI in animal models. In addition, orally administered curcumin, at a dose of
100 mg/kg 1 h prior to cisplatin treatment, attenuated cisplatin-induced autophagy in the murine
hippocampus accompanied by the activation of AMPK-JNK signaling [283] . Further, piceid, a resveratrol
derivative, given orally at a dose of 50 mg/kg/d for 4 weeks, protected against doxorubicin-induced
cognitive impairment concomitant with the up-regulation of Nrf2, inhibition of the NF-κB pathway, and
reduction of apoptosis in the rat hippocampus [284] . It seems the ameliorative potential of chemoprevention
is worthy of serious consideration.

In summary, over the past 50 years or so, many phytochemicals have been discovered and characterized
that can delay, prevent, or reverse the process of carcinogenesis, and thereby modulate the incidence
of the end stage cancer. Given the consequences of malignant metastatic disease, the promise of this
therapeutic approach is evident yet remains largely untapped. As we continue to strive for primary
intervention strategies that can be offered to all of those in need, additional potential benefits have become
apparent, some of which are described herein and depicted in Figure 14. Not only does chemoprevention
offer significant promise for disease prevention, but given the enormous economic burden imposed by
contemporary biologic and drug therapies [285] , the approach would be cost-effective.