Study On Tongue Coating And Gastric Mucosa Microbiota In Patients With Gastric Cancer Based On High Throughput Sequencing

BACKGROUND:Helicobacter pylori(Hp)was the first bacterium to be considered carcinogenic and represents the main etiologic agent in gastric cancer.Recently,an increasing pool of evidence suggests that the other non-Hp bacteria may also play a causative role in the pathophysiology of gastric cancer,and pathogens that can have an impact on cancer development in the gastrointestinal tract are also found in the oral cavity.In order to get a comprehensive understanding of the oral and gastric mucosa microbiota in GC patients,we used microbial 16 S rDNA deep sequencing to identify paired gastric mucosa and tongue coating samples in superficial gastritis(SG)and GC patients,and found that GC patients exhibited a distinct gastric microbiome profile from that observed in SG patients.PartⅠ:A comparison of the tumor-associated and non-tumor-associated gastric microbiota in gastric cancer patients Background:How gastric cancer(GC)incidence is associated with changes in the gastric microbiome has not been firmly established.The present therefore sought to survey the microbial communities present within the gastric mucosa of patients with superficial gastritis(SG)or GC.Methods:Paired tumor and non-tumor tissue samples of the gastric mucosa were collected from 18 patients being surgically treated for GC and from 32 patients with SG being treated via gastroscopy.The gastric microbiota in these samples was then profiled via 16 S rDNA sequencing,with a linear discriminant analysis(LDA)effect size(LEfSe)approach being used to identify and compare different bacteria,and with PICRUSt being used for predictive functional analyses.Results:GC patients exhibited a distinct gastric microbiota profile from that observed in SG patients.These changes were evident in both tumor and non-tumor tissues from GC patients.Specifically,we found that 6 bacterial genera were specifically enriched in GC tissue samples relative to SG samples,while 18 genera were depleted in these same samples.Based on the differential abundance of these bacteria,we were able to calculate microbial dysbiosis index(MDI)values,which were significantly higher in GC patients than in SG patients.In addition,MDI values were negatively correlated with gastric Shannon index and were positively correlated with relative Helicobacter spp.abundance.Importantly,these MDI values were readily able to discriminate between GC and SG patient samples.Functional analysis suggested that GC patients were more likely to harbor a nitrosating microbial community.Furthermore,FISH found that the average optical density(AOD)of bacteria in the lamina propria of tumor tissues was higher than that of the non-tumor tissues and SG,and the AOD of bacteria in non-tumor tissues and SG mucosal epithelium and mucosal lamina propria was positively correlated.Conclusions:GC patients exhibited a distinct gastric microbiota profile from that observed in SG patients,with these differences being evident in both tumor and non-tumor tissues.Differences in the relative abundance of Helicobacter spp.may be the primary driver of gastric dysbiosis in GC patients.Part Ⅱ:Helicobacter pylori infection Is Associated with the Co-Occurrence of Bacteria in the tongue coating and the gastric mucosa Background:Pathogens capable of impacting gastrointestinal tract tumor development are located in the oral cavity,but whether these oral bacteria are able to colonize the gastric mucosa in gastric cancer(GC)patients and whether Helicobacter pylori infection can influence this process remains to be established.Methods:Microbial 16S rDNA deep sequencing was conducted to characterize bacteria present in paired gastric mucosa and tongue coating samples in 27 patients with superficial gastritis(SG)and 11 GC patients.Results:While the overall composition of the gastric mucosa and tongue coating microbiota differed substantially,certain bacteria were present in both of these communities.The co-occurrence of bacteria between the tongue coating and gastric mucosa differed significantly between SG and GC patients.Of the 15 most abundant shared oral bacteria genera(the core shared oral bacteria)which were associated with differences in microbiota composition between these tongue coating and gastric mucosa,three were enriched in the gastric mucosa of GC patients relative to SG patients,whereas 12 were depleted in GC patient samples.Furthermore,the prevalence and relative abundance of these core shared oral bacteria in the gastric mucosa was also linked to H.pylori infection status,and the core shared oral bacteria were also associated with the overall composition of the gastric mucosal microbiota.Conclusions:H.pylori infections are linked to the co-occurrence of bacteria in the oral microbiota and the gastric mucosal microbiota.Ectopic colonization of oral microbiota may be a primary driver of H.pylori-induced gastric microbial dysbiosis in patients with GC.