FIGURE 2.

Physiological nonspecific mechanisms of probiotics for preventing and treating colorectal cancer (CRC). Probiotics produce short‐chain fatty acid (SCFA) and mediate apoptotic and anti-proliferative reactions in CRC cells. Produced SCAFs by probiotics protect the intestinal tract by preventing the histone deacetylases (HDACs) and overexpression of mucins, including MUC1, MUC3, and MUC4. SCFAs activate 5′‐adenosine monophosphate‐activated protein kinase. This is a critical factor in keeping the hypoxia‐inducible factor via SCAFs, which improves the epithelial duct’s survival and function. Probiotics elevate antimicrobial peptides, including defensin and (LL‐37) cathelicidin, from the intestinal mucosal layer. These peptides protect them against bacterial inoculation and invasion. Probiotics inhibit enzymatic activity of pathogenic bacteria, including enzymes such as nitroreductase, β‐glucuronidase, azoreductase, and β‐glucosidase. They also decrease the production of carcinogenic agents. Probiotics inhibit carcinogenic agents (N‐nitrous and heterocyclic aromatic amines [HCA]) by two mechanisms (deactivation and binding). They are potent mutagens and result in carcinogenic mutations in intestinal cells. Moreover, probiotics increase the antioxidant enzyme production and inactivate carcinogen‐deactivating agents, including glutathione reductase, glutathione‐S‐transferase (GST), superoxide dismutase (SOD), glutathione peroxidase, and catalase (CAT), and decrease their adverse effects. Besides, probiotics eliminate the risk of CRC development due to metabolites that have effects on the cytochrome p450. This figure is adapted from Eslami et al., (2019).