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.

Akkermansia muciniphila, a potential probiotic, has been proven to lessen the effects of several diseases. As established, the relative abundance of Akkermansia is positively correlated with tryptophan metabolism. However, the reciprocal interaction between tryptophan and Akkemansia is still unclear. Herein, for the first time, the possible effects of tryptophan and its derived metabolites on A. muciniphila were preliminarily investigated, including growth, physiological function, and metabolism. Obtained results suggested that 0.4 g/L of tryptophan treatment could significantly promote the growth of A. muciniphila. Notably, when grown in BHI with 0.8 g/L of tryptophan, the hydrophobicity and adhesion of A. muciniphila were significantly improved, potentially due to the increase in the rate of cell division. Furthermore, A. muciniphila metabolized tryptophan to indole, indole-3-acetic acid, indole-3-carboxaldehyde, and indole-3-lactic acid. Indoles produced by gut microbiota could significantly promote the growth of A. muciniphila. These results could provide a valuable reference for future research on the relationship between tryptophan metabolism and A. muciniphila.

Aging-related osteoporosis is considered as a serious public health concern for middle-aged and elderly people, with an intricated pathogenesis including the recently identified aging-induced immunological dysfunction and gut microbial disorder. The intervention based on dietary prebiotics is recommended to retain bone health and postpone the progression of osteoporosis. As a well-defined prebiotic, 2'-fucosyllactose (2'-FL) has been thoroughly validated with positive effect on systemic health and was proposed in this study to unveil its intervention on aging-related osteoporosis, as well as the underlying mechanisms involving the gut microecology and innate immunity. The effects of dietary 2'-FL on osteoporosis phenotypes were identified by evaluating the severity of bone loss and microstructure damage in natural aging mice. The mechanisms relying on innate immune profile, intestinal barrier function, and gut microbial homeostasis, were analyzed to elucidate the signaling axis. The detailed molecular signaling was validated based on LPS-stimulated RAW 264.7 murine macrophages. The results indicated that 12-week 2'-FL intervention retrieved bone loss and microstructure damage in natural aging mice. Also, 2'-FL alleviated aging-induced colonic inflammation, gut barrier dysfunction, and abnormal expression of intestinal tight-junction protein. The impact of 2'-FL treatment on the aging-induced gut microbial dysbiosis was validated by restoring gut microbiota diversity, recovering the abundance of Bifidobacterium, Prevotellaceae and Akkermansia, and inhibiting the growth of Stenotrophomonas. Flow cytometry analysis revealed changes in dendritic cell (DC) and macrophage subsets with age, and a decrease in M1-polarized macrophages was observed in 2'-FL-treated aged mice and RAW264.7 cells potentially through the interaction with toll-like receptor 4 (TLR4) to suppress NF-κB signaling and the secretion of proinflammatory factors. These findings highlight the preventive effect of 2'-FL on aging-associated osteoporosis by regulating gut microbial homeostasis and innate immune responses.

Sugar reduction and sugar control are advocated and gaining popularity around the world. Sucrose, as the widely consumed ingredient in our daily diet, has been reported a relation to gastrointestinal diseases. However, the role of sucrose in inflammatory bowel disease remains controversial. Hence, our study aimed to elucidate the potential role of three doses of sucrose on DSS-induced colitis in C57BL/6 mice and the underlying mechanisms. The results showed that low-dose sucrose intervention alleviated colitis in mice, reducing the expression of inflammatory cytokines and repairing mucosal damages. In contrast, high-dose sucrose intervention exacerbated colitis. Furthermore, three doses of sucrose administration markedly altered gut microbiota composition. Notably, the low-dose sucrose restored microbial dysfunction and enhanced the production of short chain fatty acids (SCFAs). Specifically, the abundance of SCFAs-producing bacteria Faecalibaculum, Bacteroides, and Romboutsia were increased significantly in the LOW group. Consistently, PPAR-γ, activated by SCFAs, was elevated in the LOW group, thereby inhibiting the MAPK/NF-κB pathway. Together, our study demonstrates the differential effects of sucrose on colitis at different doses, providing a scientific basis for measuring and modifying the safe intake level of sugar and providing favorable evidence for implementing sugar reduction policies.