Abstract
Coarse cereal intake has been reported to be associated with reduced risk of colorectal cancer. However, evidence from intervention studies is absent and the molecular basis of this phenomenon remains largely unexplored. This study sought to investigate the effects of foxtail millet and rice, two common staple grains in Asia, on the progression of colitis-associated colorectal cancer (CAC) and define the mechanism involved. In total, 40 BALB/c mice were randomized into four groups. The Normal and azoxymethane/dextran sodium sulfate (AOM/DSS) groups were supplied with an AIN-93G diet, while the millet- and rice-treated groups were supplied with a modified AIN-93G diet. Compared to the AOM/DSS-induced CAC mice supplemented with rice, an increased survival rate, suppressed tumor burden, and reduced disease activity index were observed in the millet-treated group. The levels of IL-6 and IL-17 were decreased in the millet-treated group compared to both the AOM/DSS and AOM/DSS + rice groups. Millet treatment inhibited the phosphorylation of STAT3 and the related signaling proteins involved in cell proliferation, survival and angiogenesis. These beneficial effects were mediated by the activation of gut receptors AHR and GPCRs via the microbial metabolites (indole derivates and short-chain fatty acids) of foxtail millet. Moreover, millet-treatment increased the abundance of Bifidobacterium and Bacteroidales_S24-7 compared to the rice-treated mice. This study could help researchers to develop better dietary patterns that work against inflammatory bowel disease (IBD) and for CAC patients.
Highlights
According to the latest data from the American Cancer Society, colorectal cancer (CRC) is the third most diagnosed and second most deadly cancer, seriously threatening human health [1]
The Disease activity index (DAI) values were significantly reduced from Week 5 to the end of the study, in the millet-treated group compared to the azoxymethane/dextran sodium sulfate (AOM/dextran sodium sulfate (DSS)) + rice group (Figure 2C)
By the end of the treatment, a significant difference in the DAI was not observed between the AOM/DSS + millet mice and the AOM/DSS mice, but a significant reduction in the indexes of the millet-treated mice was observed during the first recovery period and the second treatment of DSS
Summary
According to the latest data from the American Cancer Society, colorectal cancer (CRC) is the third most diagnosed and second most deadly cancer, seriously threatening human health [1]. The morbidity and mortality of CRC has increased continuously, especially in some developing countries [2]. Nutrients 2020, 12, 2367 tract that is mediated by abnormal immunity and has a tendency to relapse, has been reported to be an important inducer of CRC [3,4]. Epidemiological studies have suggested that IBD patients exhibit a higher risk of CRC and that the incidence of cancer is positively correlated with the duration of IBD [4,5]. The increased pro-inflammatory cytokine release and altered signaling pathways associated with IBD play vital roles in the development of colitis-associated and sporadic CRC [2]. Because prevention is better than a cure, intervention at the points of intestinal inflammation and early-stage tumorigenesis is of great significance in controlling the morbidity and mortality of CRC
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