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Research On Composition And Diversity Of Gastrointestinal Microbiota In Gastric Cancer Patients

Posted on:2020-04-10Degree:DoctorType:Dissertation
Country:ChinaCandidate:W R LiangFull Text:PDF
GTID:1364330578478596Subject:Oncology
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Part ? The composition and diversity shifts of gut microbiota in patients with gastric cancerBackground Gastric cancer is one of the most common malignant tumors in China,with a high morbidity and mortality.With the development and application of high-throughput sequencing technologies and metagenomics,studies have shown that gastrointestinal microbiota is closely related to digestive system diseases.Although some studies have reported the long-term effect after subtotal gastrectomy on intestinal flora changes in patients with gastrie eancer.The features of gut microbiota and their shifts in patients with gastric cancer in perioperative period remain unclear.Aims This study was designed to characterize fecal microbiota shifts of the patients with gastric cancer before and after the radical distal gastrectomy(RDG)during their hospital staying periods.Short-chain fatty acids(SCFAs)are key end-productions of bacterial fermentation,and the changes of SCFAs concentrations were also discussed in this study.Furthermore,in order to find potential gut microbiota features in patients with gastric cancer,the gut microbiota were also compared between the gastric cancer patients and healthy individuals.Methods Patients who were diagnosed with advanced gastric cancer at distal stomach were enrolled in the study.The bacterial burden within fecal samples was determined using quantitative PCR.To analyze the diversity and eomposition of gut microbiota fecal DNA from 20 gastric cancer patients and 22 healthy controls were collected,amplicons of the 16S rRNA gene from all subjects were sequenced.To study gut microbiota shifts,the fecal microbiota from 6 gastric cancer patients before and after RDG were detected and subsequently analyzed.Finally,the changes of fecal SCFA concentrations after surgery was detected by gas chromatography spectrometer.Results Higher abundances of Escherichia/Shigella,Veillonella and Clostridium ??and lower abundances of Bacteroides were observed in gut microbiota of overall gastric cancers patients compared to healthy controls.Radical distal gastrectomy had a moderate effect on bacterial r:ichness and evenness,but with pronounced effects on the composition of postoperative gut microbiota,comparing with preoperative group.The relative abundances of genera Akkermansia,Esherichia/Shigella,Lactobacillus,and Dialister were significant changed in perioperative period.A significant decreased concentration of Valerate after surgery was observed.The declining trends in other major SCFAs(i.e,Acetate,Propionate,Butyrate)were also founded.Conclusion In conclusion,the 16S rRNA gene based high through sequencing had showed vast bacterial community in fecal salples of gastric cancer patients and healthy individuals,within unique microbial composition and diversity.Significant gut microbiota compositional changes have been observed in patients with gastric cancer after RDG,whereas there was no signifieant difference in diversity.Part ? The difference of composition and.diversity from gastric microbiota in patients with proximal and distal gastric cancerBackground According to the tumor location,gastric cancer(GC)can be divided into proximal GC and distal GC.In recent years,the incidence and mortality of GC worldwide have showed a trend of deeline.However.a steady rise in the incidence of adenocarcinoma of the proximal stomach and gastro-oesophageal junction has been observed.There are significant differences between distal and proximal GC in etiology,including histological origins,clinicopathological features and prognosis.However,so far,only a few studies were performed to investigate the composition of gastrointestinal tract microbiota under health and disorders based on the sequencing methods.Studies on the links between microbiota of the stomach and GC are scarce.Above all.it is necessary to investigate that whether the gastric microbiota in patients with GC is different from that in different locations and whether the gastric dysbiosis contributes to the pathogenesis of gastric disorders.Aims In this study,we aim to explore the composition and diversity characteristics of the microflora in the patients with proximal and distal GC,and to make a eomparative analysis of the microbiota of the two types of GC.Methods Patients with proximal and distal GC in our hospital who were initially diagnosed by endoscopy and confirmed by pathology were enrolled.We investigated the diversity and composition of the gastric microbiota from 5 proximal GC patients and 5 distal patients with GC by using sequencing techniques.Tumor tissues were collected intraoperatively,and normal gastric mucosa sample was taken in the distance.Bacterial DNA of gastric microbiota was isolated,then the high-throughput community sequencing was performed.Bioinformatics software was applied to analyze the data.Results There were pronounced differences in the microbial composition between proximal and distal GC.Microbial community in the distal GC group was mainly composed of Firmicutes and Proteobacteria,and more than 50%of the microflora in the distal CGC tumor tissue belongs to Firmieutes.Proteobacteria,Acidobacteria and Actinomycetes were the top phyla in the proximal GC group.Proteobacteria was the most dominant taxa in the proximal GC group.The abundanee of Firmicures in the proximal GC group was lesser than that in the distal GC group.Conclusion Our data verified that the microbial diversity and structure of gastric microbiota in different regions indicating that identifying key functional taxa of the complexed microbial community maybe helpful to improve outcome for gastric cancers.
Keywords/Search Tags:Gastric cancer, 16S rRNA gene sequencing, Microbiota, Gastrectomy, Diversity, Distal gastric cancer, Proximal gastric cancer, Bacterial microbiota, Diagnose and treatment
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