The stilbenoids form a group of bioactive phenolic compounds found in various plant species whose original functions are to act as protective compounds against microbial infections and toxins. Among the stilbenoids, resveratrol is the most well-studied and has been shown to exert multiple benefits in disease prevention. The bioavailability of resveratrol is one of the major limitations in its role as a disease-prevention agent; however, it has exhibited biological activity in animals and clinical models. Gut microbiota may play a role in overcoming limited bioavailability via microbial transformations. On the other hand, the modulatory effects of stilbenoids on gut microbial dysbiosis induced by several diseases can be crucial in disease alleviation. In addition to gut microbial metabolites, such as SCFAs (short-chain fatty acids), stilbenoids can be used to inhibit microbial growth, making their use a potential strategy in preventing disease progression. In this review, the interactions of stilbenoids (with a major focus on resveratrol and pterostilbene) and gut microbiota will be discussed to clarify the importance of gut microbiota in the strategy of “disease prevention via phytochemicals.”

Evidence shows that the dietary intake of polycyclic aromatic hydrocarbons (PAHs) from food processing induces the cellular DNA damage response and leads to the development of colorectal cancer (CRC). Therefore, protecting from cellular DNA damage might be an effective strategy in preventing CRC. Benzo[a]pyrene (B[a]P) was used as a CRC initiator in the present study. Compared with other stilbenoids, piceatannol (PIC) showed the most effective inhibition of B[a]P-induced cytochrome P450 1B1 (CYP1B1) protein expression in NCM460 normal human colon epithelial cells. PIC treatment alleviated DNA migration and enhanced the expression of DNA-repair-related proteins, including histone 2AX (H2AX), checkpoint kinase 1 (Chk1), and p53, in B[a]P-induced NCM460 cells. The 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, flow cytometry, and enzyme-linked immunosorbent assay (ELISA) revealed that PIC exerted antioxidative effects on NCM460 cells by increasing the glutathione (GSH) content and scavenging the excess intracellular reactive oxygen species (ROS) induced by B[a]P. Furthermore, PIC suppressed B[a]P-induced CYP1B1 protein expression and stimulated miR-27b-3p expression. The upregulation of phase II detoxification enzymes, such as nicotinamide adenine dinucleotide phosphate (NADPH) and quinone oxidoreductase 1 (NQO1), and the antioxidative enzyme, heme oxygenase 1 (HO-1), via the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway was observed in the PIC-treated group. Our results suggest that PIC is a potential CRC-blocking agent due to its ability to alleviate DNA damage, decrease intracellular ROS production, modulate the metabolism and detoxification of B[a]P, and activate the Nrf2 signaling pathway in B[a]P-induced NCM460 cells.