Thai Fermented Soybean (Thua-Nao) Prevents Early Stages of Colorectal Carcinogenesis Induced by Diethylnitrosamine and 1,2-Dimethylhydrazine Through Modulations of Cell Proliferation and Gut Microbiota in Rats

Thua-nao is a traditional fermented soybean product widely consumed in the northern areas of Thailand. There has been little research on the biological activity of Thua-nao, particularly its anticancer properties. The objective of this study was to examine the cancer chemopreventive effects of dried Thua-nao on liver and colorectal carcinogenesis induced by carcinogens in rats. Rats were injected with diethylnitrosamine (DEN) and 1,2-dimethylhydrazine (DMH) to induce preneoplastic lesions. Rats orally received dried Thua-nao for 13 weeks. The preneoplastic lesions, including glutathione -transferase placental form (GST-P)-positive foci and aberrant crypt foci (ACF), were evaluated in the liver and colon, respectively. The cancer chemopreventive mechanisms of dried Thua-nao on liver and colorectal carcinogenesis were examined. Dried Thua-nao administration suppressed colorectal aberrant crypt foci. Moreover, dried Thua-nao reduced proliferation cell nuclear antigen (PCNA)-positive cells in the colon. Interestingly, dried Thua-nao modulated the gut microbiota in DEN- and DMH-induced rats. Isoflavones, including genistein and daidzein, represent promising chemopreventive agents in dried Thua-nao. In conclusion, these results highlight the cancer chemopreventive effect of dried Thua-nao in DEN and DMH-induced colorectal carcinogenesis through cell proliferation reduction and gut microbiota modulation.