Alterations of gastric mucosal microbiota across different stomach microhabitats in a cohort of 276 patients with gastric cancer

Abstract

BackgroundAs part of the tumor microenvironment, the gastric microbiota play vital roles in tumor initiation, progression and metastasis, but stomach microhabitats are not always uniform. We aimed to characterize differences of gastric microbiota in stomach microhabitats associated with gastric cancer (GC) development.MethodsA cohort of 276 GC patients without preoperative chemotherapy was enrolled retrospectively, and 230 normal, 247 peritumoral and 229 tumoral tissues were obtained for gastric microbiota analysis targeting the 16S rRNA gene by MiSeq sequencing. The microbial diversity and composition, bacterial co-occurrence correlations and predictive functional profiles were compared across different microhabitats.FindingsGC-specific stomach microhabitats, not GC stages or types, determine the composition and diversity of the gastric microbiota. Most notably, bacterial richness was decreased in peritumoral and tumoral microhabitats, and the correlation network of abundant gastric bacteria was simplified in tumoral microhabitat. Helicobacter pylori (HP), Prevotella copri and Bacteroides uniformis were significantly decreased, whereas Prevotella melaninogenica, Streptococcus anginosus and Propionibacterium acnes were increased in tumoral microhabitat. Higher HP colonisation influenced the overall structure of the gastric microbiota in normal and peritumoral microhabitats. PiCRUSt analysis revealed that genes associated with nucleotide transport and metabolism and amino acid transport and metabolism were significantly enriched in tumoral microbiota, while gastric acid secretion was significantly higher in HP positive group of the tumoral microbiota.InterpretationOur present study provided new insights into the roles of gastric microbiota in different stomach microhabitats in gastric carcinogenesis, especially the pathogenesis of HP.FundNational Natural Science Foundation of China.

The Presence of Periodontal Pathogens in Gastric Cancer

“…In all data sets, we found gastric mucosa samples completely exempt of H. pylori, including in normal and peripherical samples, which opens the possibility that other pathogens play a role in GC. We did not find H. pylori in significant interaction, which is unexpected and discrepant to findings on the same data set SRP128749 reported [Liu et al 2019]. We attribute this discrepancy to the use of a more stringent ecological network inference [Kurtz et al 2015].…”

“…Most eligible data sets are from China, Table 1. Scientific publication has been issued for the following projects: PRJEB21497 [Yap et al 2016], PRJEB21104 [Parsons et al 2017], PRJEB22107 [Klymiuk et al 2017], PR-JNA428883 [Liu et al 2019] and PRJNA495436 [He et al 2019]. For the purpose of comparison, we also revisited five published colorectal cancer (CRC) data sets, Table 2.…”

“…In recent years, other bacteria have been proposed as risk factors for GC, including Propionibacterium acnes and Prevotella copri [Gunathilake et al 2019], Fusobacterium nucleatum [Yamamura et al 2017, Hsieh et al 2018 and Leptotrichia wadei [Yang et al 2016]. Prevotella melaninogenica, Streptococcus anginosus and P. acnes have been reported increased in the tumoral microhabitat [Liu et al 2019]. The centrality of Peptostreptococcus stomatis, S. anginosus, Parvimonas micra, Slackia exigua and Dialister pneumosintes in GC tissue has been reported [Coker et al 2018].…”

Prevention of gastric cancer by Helicobacter pylori eradication: A review from Japan

“…According to the gastric microbiota profile generated by 16S rRNA analysis, many other bacteria exist in the stomach besides H pylori . Chinese researchers confirmed that H pylori was less common in the tumoral microhabitat than nontumoral microhabitats by conducting a gastric microbiota analysis targeting the 16S rRNA gene in 230 normal, 247 peritumoral and 229 tumoral tissues . H pylori colonization alone is not sufficient to induce gastric carcinogenesis, and H pylori ‐induced gastric cancer is promoted by the presence of a complex microbiota .…”

“…53 H pylori colonization alone is not sufficient to induce gastric carcinogenesis, and H pylori-induced gastric cancer is promoted by the presence of a complex microbiota. 53 Furthermore, dysbiosis of the microbiome in the stomach, which is involved in the development of gastric cancer, occurs when the relative abundance of H pylori decreases. 54 Research from Portugal suggested that the gastric microbiome in patients with gastric carcinoma exhibits a dysbiotic microbial community (eg, nitrosating bacteria) with genotoxic potential.…”