Effects Of Antibiotics And Inulin On Colon Cancer And Pulmonary Metastasis Based On Regulating Microbiota

Colon cancer is one of the common malignant tumors that endanger human health.Intestinal microbiota plays an important role in the occurrence of colon cancer.Antibiotics and inulin,as modulators of intestinal microbiota,may affect the progression of colon cancer by regulating intestinal microbiota.To verify this hypothesis,we conducted the following experiments.We constructed CT26 colon cancer solid tumor model and pulmonary metastasis model.The results showed that mixed antibiotics(metronidazole,neomycin sulfate,ampicillin and vancomycin)could inhibit solid tumor and pulmonary metastasis of colon cancer.Inulin could not significantly inhibit pulmonary metastasis.It was found that antibiotics significantly inhibited microbiota associated with colon cancer,such as Streptococcus,Desulfovibrio,Helicobacter,Ruminococcus and Lactococcus.The regulatory effect of inulin on these bacteria was not obvious,which might be the reason why inulin and antibiotics had different therapeutic effects.In addition,antibiotics and inulin also regulated bile acids related microbiota.They affected bile acids of liver and intestinal contents.Antibiotics significantly reduced content of lithocholic acid(LCA)and deoxycholic acid(DCA).This was also one of the reasons for inhibiting pulmonary metastasis.Although mixed antibiotics had good effects in the treatment of solid tumors of colon cancer and pulmonary metastasis.They also had obvious side effects,including weight loss,reduction of spleen index and liver index,as well as reduction of short chain fatty acids(SCFAs).Rifaximin is a safe broad-spectrum antibiotic which had been marketed.Therefore,we studied effects of rifaximin and its combination with inulin on pulmonary metastasis of colon cancer.The results showed that therapeutic effect of rifaximin alone was accidental.About 35% of mice had significantly reduced pulmonary metastasis.About 65% of mice not only did not inhibit pulmonary metastasis,but also had brain metastasis.However,rifaximin combined with inulin significantly inhibited pulmonary metastasis without any brain metastasis.They had no obvious toxic and side effects,prolonged survival time of mice.According to analysis of intestinal microbiota,rifaximin or inulin alone could not significantly affect bacteria associated with colon cancer,but the combined group significantly reduced these bacteria,such as Actinobacteriota,Streptococcus,Desulfovibrio,Bacteroides and Lactococcus.In addition,rifaximin combined with inulin regulated the bacteria related with bile acids,such as Bacteroides,Actinobacillus and Bifidobacterium.They increased content of primary bile acids in liver and intestinal contents,and reduced content of secondary bile acids.DCA and LCA,as agonists of TGR5 receptor,inhibited expression of TGR5 receptor in lung after their contents were reduced.After TGR5 receptor was inhibited,NF-κB p65 also was inhibited.Therefore,they promoted secretion of TNF-αand blocked the cycle of lung tumors.Rifaximin and inulin alone could not inhibit the expression of TGR5 receptor.Above results might be the reason for the better effect of the combined treatment.In conclusion,rational use of intestinal microbiota regulators can effectively treat colon cancer and pulmonary metastasis.The above research provided a new idea for the treatment of cancer.