Analysis Of Fecal Microbiota In Patients With Digestive Tract Tumors And The Potential Correlation Between Microbiota And Curative Effect And Prognosis

Background and aim:The incidence and mortality of gastrointestinal cancer are high in China.The occurrence and development of gastrointestinal cancer are considered to be related to many factors.Bacteria in human gut are proved to play a role in physiological process like nutrient metabolism and immune regulation.Intestinal bacteria is found to be related to the occurrence and development of tumors and other diseases.Some species also have some impacts on the efficacy and adverse events of anti-cancer therapy.At present,there is no prospective study targeting at the correlation between gastrointestinal tumors and intestinal bacteria in Chinese population,and the reports on the profile of bacterial flora in upper gastrointestinal tumors is limited to the samples of esophageal and gastric flora.The aim of this study was to explore the differences of fecal microbiota among esophageal cancer,gastric cancer,colorectal cancer patients and healthy people,and to analyze the correlation between the microbiota and the efficacy and adverse reactions of anti-neoplastic therapy.We also aimed to find microbial biomarkers that may potentially predict the prognosis of chemotherapy.Methods:In this study,prospective and sequential grouping methods were used to include patients with locally advanced or metastatic esophageal,gastric and colorectal cancer who were to receive chemotherapy or immunotherapy,and healthy people as controls.Clinical information was collected.Fecal specimens were collected before treatment and at the first assessment(6-8 weeks).Peripheral blood samples were collected before treatment to detect inflammatory indicators,whole blood cells and lymphocyte analysis.Fecal specimens were collected from healthy people once.16S rRNA sequencing was used to analyze the composition and abundance difference of fecal bacteria.The sequencing data were processed by FLASH and USEARCH software,and the species annotation was compared with the database Greengene.R language was used for flora analysis,PICRUSt software was used for functional prediction,and statistical methods were used to compare the differences between groups.Results:From April 2018 to April 2020,130 patients with gastrointestinal tumors were enrolled into this study.Forty cases were esophageal cancer,forty six cases were gastric cancer and forty four cases were colorectal cancer.The median follow-up time was 11 months.A total of 15 phylum-level bacteria were detected in feces by 16S rRNA sequencing.(1)The abundance of F.prausnitzii,C.clostridioforme and B.adolescents in three different tumor groups was significantly lower than that in the control group(P<0.05,FDR<0.05).The abundance of B.obeum and R.faecis in gastric cancer group and in colorectal cancer group was significantly lower than that in control group(P<0.05,FDR<0.05);the abundance of Butyricicoccus pullicaecorum bacteria in gastric cancer and colorectal cancer group was significantly lower than that in the control group(P<0.05,FDR<0.05).The abundance of B.fragilis,A.muciniphila,Clostridium hathewayi and Alistipes finegoldii in different tumor groups was significantly higher than that in healthy control group(P<0.05,FDR<0.05).There was significant difference in functional metabolism and cell biological function between the two groups(P<0.05,FDM<0.05).(2)The abundance of B.plebeius tended to increase in the feces of patients with PR after chemotherapy(P<0.05,FDR>O.05)compared to SD.The fecal sample of two patients with PR after immunotherapy had high abundance of F.prausnitzii(twice)and B.plebeius(4 times).The abundance of Roseburia faecis in PD patients decreased significantly compared with baseline,while in effective patients(SD+PR),the abundance of R.faecis increased or decreased slightly,and the difference was statistically significant(P=0.024).After chemotherapy,the abundance of R.faecis decreased significantly in patients with PD in esophageal cancer group,while the abundance of R.faecis increased mainly in PR group(P=0.019).During chemotherapy,the higher the abundance elevation of R.faecis was,the more likely the chemotherapy would be effective(ROC:sensitivity 85.7%;specificity 76.1%).There was no significant difference in PFS between the two groups(abundance of R faecis increased versus decreased)after treatment.(3)There were more E.coli and B.plebeius in the feces of patients with grade 3-4 chemotherapy-related adverse reactions,and more B.plebeius in the feces of patients with severe immune-related adverse reactions.Conclusions:Patients with esophageal cancer and gastric cancer had similar features of fecal bacteria with butyrate-producing bacteria consuming significantly as those with colorectal cancer.The baseline abundance and abundance variation of some differential speices may have potential clinical significance in predicting the efficacy of chemotherapy for esophageal cancer,gastric cancer and colorectal cancer.If abundance of Roseburia faecis increases after chemotherapy,the possibility of effective treatment increases.