Polyphenol from foxtail millet bran alleviates experimental colitis in mice by remodulating intestinal fungal community

Inflammatory bowel disease(IBD)is a chronic relapsing-remitting systemic disease of the gastrointestinal tract,characterized by an inflammatory process.Gut mycobiota community dysbiosis has been reported that is closely related to the development of IBD.Our previous findings indicated that polyphenol of the inner shell(BPIS)from foxtail millet bran could restore the gut microbiome and inhibit the progress of colorectal cancer(CRC).In the present study,we studied the anti-inflammatory potential of BPIS in the dextran sodium sulfate(DSS)-induced mouse colitis model.Data suggested that BPIS alleviated experimental colitis by restoring body weight,colonic length and protecting the epithelial architecture from damage by DSS.Moreover,we found that BPIS strengthened the gut barrier function and inhibited the activation of Wnt1/β-catenin pathway.Gene sequence analysis indicated that BPIS remodeled the overall structure of the gut mycobiota from colitis mice toward that of the normal counterparts,including 1 phylum and 9 genera.Interestingly,BPIS significantly increased the abundance of Aspergillus ruber.It further verified that BPIS significantly promoted the growth of A.ruber in vitro.Collectively,BPIS has great potential to develop into an effective against IBD drug.

Gut microbiota remodeling drived by dietary millet protein prevents the metabolic syndrome

Metabolic syndrome(Met S)is a chronic disease associated with the disturbance of gut microbiota homeostasis.Metabolites derived from gut microbes play essential roles in Met S prevention and therapy.Here,we focused on the inhibitory effect of the extract of millet bran protein(EMBP)on a high-fat diet(HFD)-induced Met S,aiming to identify gut microbiota and their metabolites that involve in the anti-Met S activity of EMBP.The obesity,chronic inflammation,insulin resistance in Met S mouse models were abolished after EMBP treatment.The protective mechanism of EMBP against HFD-induced Met S may depend on improved gut barrier function.Using microbiome analysis,we found that EMBP supplementation improved gut microbiome dysbiosis in Met S mice,specifically upregulating Bacteroides acidifaciens.The fecal microbiota transplantation(FMT)also demonstrated this phenomenon.In addition,metabolomic analysis showed that EMBP mediates metabolic profiling reprogramming in Met S mice.Notably,a microbiota-derived metabolite,gamma-aminobutyric acid(GABA),is enriched by EMBP.In addition,exogenous GABA treatment produced a similar protective effect to EMBP by improving NRF2-dependent gut barrier function to protect HFDinduced Met S.The results suggest that EMBP suppress host Met S by remodeling of gut microbiota as an effective candidate for next-generation medicine food dual purpose dietary supplement to intervene in MetS.

Peroxidase from foxtail millet bran exerts anticolorectal cancer activity via targeting cellsurface GRP78 to inactivate STAT3 pathway

Molecular targeted therapy has become an emerging promising strategy in cancer treatment,and screening the agents targeting at cancer cell specific targets is very desirable for cancer treatment.Our previous study firstly found that a secretory peroxidase of class III derived from foxtail millet bran(FMBP)exhibited excellent targeting anti-colorectal cancer(CRC)activity in vivo and in vitro,whereas its underlying target remains unclear.The highlight of present study focuses on the finding that cell surface glucose-regulated protein 78(cs GRP78)abnormally located on CRC is positively correlated with the anti-CRC effects of FMBP,indicating it serves as a potential target of FMBP against CRC.Further,we demonstrated that the combination of FMBP with the nucleotide binding domain(NBD)of cs GRP78interfered with the downstream activation of signal transducer and activator of transcription 3(STAT3)in CRC cells,thus promoting the intracellular accumulation of reactive oxygen species(ROS)and cell grown inhibition.These phenomena were further confirmed in nude mice tumor model.Collectively,our study highlights cs GRP78 acts as an underlying target of FMBP against CRC,uncovering the clinical potential of FMBP as a targeted agent for CRC in the future.