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Effect of Disordered Gut Microbiota on Serum Metabolome Alterations in Colorectal Tumor-Bearing Mice Under The Intervention of Fufangchangtai


 Background: The occurrence and development of colorectal cancer is related to the compositional and functional variation of gut microbiota. Compared with healthy people, gut microbiota of patients with colorectal cancer is in disorder. Most traditional Chinese Medicine is effective by oral administration and has both anti-tumor effect and enteric microecological regulative effect. However, whether the dysbiosis of gut microbiota under tumor burden affects the serum metabolome of human body that related to traditional Chinese medicine is unclear. In this study, Fufangchangtai (FFCT) was chosen to be the model prescription to explore the correlation between gut microbiota and the serum metabolism related to FFCT in anti colorectal cancer treatment. Results: The gut microbiota between colorectal tumor-bearing mice and healthy mice were determined by 16S rRNA gene sequencing, showing quite differences between the two groups and suggesting that Firmicutes , Deferribacteres , Bacteroidetes and Proteobacteria were marked differential intestinal bacteria. The alternations in serum metabolome in the FFCT-treating tumor-bearing mice and simple FFCT-treating mice were detected using Liquid chromatogragh-mass spectrometer (LC/MS), showing significant differences between the two groups as well. Metabolites of FFCT like Citric acid, （±）12-HEPE, Cycloartanyl ferulate were much more in simple FFCT-treating mice, indicating that the present of tumor could affect the absorption and metabolism of FFCT. Additionally, these differential metabolites of FFCT involved in multiple pathways including the Alanine, aspartate and glutamate metabolism, Central carbon metabolism in cancer, Biosynthesis of amino acids. Different doses of FFCT were given to the tumor-bearing mice through oral administration, and the results of gut microbiota 16S rRNA gene sequencing showing that FFCT-treating groups has higher abundance of Firmicutes , Turicibacter and Roseburia than tumor-bearing group, moreover, the abundance of these bacteria was positively correlated to the drug concentration. Firmicutes and Bacteroidetes in FFCT-treating groups showed a similar trend with Healthy group, indicating the modulation of FFCT on gut microbiota of colorectal tumor-bearing mice.Conclusions: Collectively, we concluded that the dysbiosis of gut microbiota in tumor-bearing mice could affect the serum metabolome of human body that related to FFCT, and FFCT could correct the gut microbiota of colorectal tumor-bearing mice. It was pointed out that the GM should be concerned during the therapy of FFCT. The more healthier intestinal microenvironment was conductive to the better clinical curative effect.