Comparative Effects Of Two Functional Polysaccharides On Colitis And Colon Cancer

With the change of dietary structure,the incidence of some common intestinal diseases such as colitis and colon cancer,which seriously damaged human health due to their repeated and long cause and crypticity,has been on the rise year by year.A large number of studies have found that diets with dietary polysaccharide play an important role in the regulation of gut microbes,inhibition of inflammatory responses and reduction of intestinal immune stress.However,there was no systematic comparision about the mechanism of different polysaccharides improving human health.In this research,the beneficial effects and mechanism of two functional polysaccharides,?-glucan and guar gum,on the intestinal health were compared.These two polysaccharides were first processed individually as feeds to intervene the normal animals as well as the colitis and colon cancer models.The effects on the gut microbes and gene expression in colon epithelial cells were then analyzed via sequencing of microbial community diversity and RNA sequencing,respectively.The result showed that:1)The effect of ?-glucan diet on colitis rats was achieved by adjusting the structure of gut microbes,increasing the relative abundances of the phylum Firmicutes,the genus Ruminococcus₁,Fusicatenibacter and Paraprevotella,and inhibiting the phylum Proteobacteria,the genus Escherichia-Shigella and Sutterella,thereby generating more SCFAs which can protect intestinal mucosa and colonic epithelial cells.In addition,?-glucan also up-regulated TRBV,LCK,CCL5,IL21 R,CD8A and CD3 E gene,thus promoting immune function and cytokine secretion and affecting inflammatory response.It also down-regulated seven genes including PTGS2?COX2?,CXCL1,CXCL2,CXCL3,CCL3,IL11 and MHC2,thereby reducing rat's inflammatory response,protecting intestinal mucosa and the integrity of intestinal epithelial cells,and preventing the transition from normal colonic epithelial cells to cancer cells.Therefore,the intestinal health was maintained.2)The effect of guar gum diet on colitis rats was achieved by regulating the gut microbial structure.For example,increasing the relative abundances of the phylum Actinobacteria,the genus Bifidobacterium,Ruminococcus₁,Romboutsia and Turicibacter,and inhibiting the genus Streptococcus,Barnesiella,Anaerotruncus and unknown genus of Lachnospiraceae,thereby increased the growth of beneficial bacteria and then the production of SCFAs in intestine,and reduced intestinal inflammation.Besides,it also altered the gene expression in colon epithelial cells.The intervention up-regulated four genes including CXCL11?I-TAC?,DDX58?RIGI?,CXCL10?IP10?and IRF7,thereby strengthened the immune response.Meanwhile,the intervention also down-regulated 15 genes including PTGS2?COX2?,CD14,LBP,PLAU,MCP1?CCL2?,CXCL1,CXCL2,CXCL3,JUN,TLR2,IL11,CD3 D,RAC2,RORC?NR1F3?and MHC2 genes,thereby alleviated the damage of inflammatory factors to the intestinal mucosa,liver and cardiomyocytes,and then prevented the colorectal cancer transition from colitis and further inhibited the formation of cancer cells.3)The intervention of ?-glucan diet in colon cancer mice prevented colon from shortening,reduced colon damage and 30 % of the mortality.These effects were possibly achieved by inhibiting those gut bacteria?such as lower the abundance of the genus Oscillospira and unknown genus of the family Desulfovibrionaceae?potential related to the occurrence of colon cancer.In addition,?-glucan intervention downregulated four cancer-related genes,HSPA8,GCNT2,HMGN3?TRIP7?and CYP1B1 genes,which can reduce colon cancer damage to the body.4)The intervention of guar gum in colon cancer mice was less efficient than ?-glucan,and only reduced 10 % of the mortality without significantly recovery on the physiological health of the colon and gut microbes.However,the guar gum diet can increase the relative abundances of Actinobacteria and Bacteroides,and inhibit some bacteria possibly related to disease,such as Proteobacteria,TM7 and Clostridium.Besides,the intervention of guar gum diet regulated the gene expression of colon epithelial cells such as down-regulatiing 13 genes including LIPE,ATP1A2,CD36,FABP4,LPL,SCD-1,AKR1C3,SCT,ACAA1 B,MGLL,CES1 G,DGAT2 and CA-1,and thereby played an important role in limiting the energy uptake of tumor formation and metastasis,and slowed the tumor development.Based on the results above,for the colitis,3 strains of bacteria altered by the ?-glucan diet were completely different from those 4 strains of bacteria regulated by the guar gum diet;therefore,the key bacteria of intestinal flora regulated by ?-glucan and guar gum were different.Additionally,the ?-glucan diet up-regulated 6 genes while the guar gum diet only up-regulated 4 genes,and none of which were the same.Besides,the ?-glucan diet down-regulated 7 genes while the guar gum diet down-regualted 15.Though 6 genes were shared between the down-regulating genes of ?-glucan and guar gum diet,the key genes in the colon epithelial cells regulated by these two polysaccharides were also different.For colon cancer,the ?-glucan diet can inhibit the bacteria of genus Oscillospira and family Desulfovibrionaceae,and down regulate the 4 genes related to cancer,while guar gum cannot restore the intestinal microbial diversity,but can adjust 13 genes,and are completely different from those down-regulated by ?-glucan diet.Therefore,both ?-glucan and guar gum can alleviate the damage caused by colitis and colon cancer with different efficacy and mechanism.