Dietary Supplementation of Foxtail Millet Ameliorates Colitis-Associated Colorectal Cancer in Mice via Activation of Gut Receptors and Suppression of the STAT3 Pathway

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.

The Beneficial Effect of Coarse Cereals on Chronic Diseases through Regulating Gut Microbiota

“…Zhang et al reported that intake of foxtail millet ameliorated AOM/DSS-induced colitis-associated CRC in mice via the activation of AHR and GPCRs and the inhibition of STAT3 phosphorylation by the microbial metabolites of the foxtail millet. In line with a previous study, the abundances of Bifidobacterium and Bacteroidales_S24-7 were increased after millet consumption, compared to the control group [36]. Similarly, Yang et al studied the effect of sorghum in an HFD-induced CRC mice model.…”

Dose-Dependent Beneficial Effects of Tryptophan and Its Derived Metabolites on Akkermansia In Vitro: A Preliminary Prospective Study

“…The supernatant was then filtered by 0.22 μm membrane. The concentrations of tryptophan metabolites were separated and analyzed using the method described in the previous study [ 15 ]. Operating parameters in MRM-mode are shown in Supplementary Table S1 .…”

Protective effects of bioactive peptides in foxtail millet protein hydrolysates against experimental colitis in mice

“…7 Our previous study showed that the intake of a foxtail millet-rich diet prevented the progression of colitis and colorectal cancer in mice. 8 However, the active ingredient of foxtail millet remains to be explored. Protein is a major ingredient of foxtail millet, accounting for 11%-18% of the total weight.…”