Gastric Mucosa-Associated Microbial Signatures of Early Gastric Cancer

Abstract

Alterations in the microbiome are associated with the development of gastric cancer. Our study aimed to identify dysbiotic features in early gastric cancer (EC). The gastric microbiome was assessed in EC (n = 30), advanced gastric cancer (AC) (n = 30), and chronic gastritis (CG) (n = 60). The results demonstrated significant differences in the microbial profile and composition between EC and AC, suggesting alterations associated with gastric cancer progression. Linear discriminant analysis (LDA) effect size (LEfSe) analyses identified 32 bacterial genera that were associated with EC. Functional analyses of the gastric microbiome showed that the production of urease and synthesis of bacterial flagella were weakened in EC, while the glycolysis of fructose and hydrolysis of glycosides were enhanced. A classifier based on a random forest (RF) machine learning algorithm identified a microbial signature that distinguished EC from CG or AC with high accuracy. The correct identification of the signature was further validated in independent cohorts. This signature enriched of bacteria with varied abundance, high degree of bacterial interactions and carcinogenic potentials. Constrained principal coordinate analyses revealed that the presence of Helicobacter pylori and the cagA and vacA virulence genotypes influenced the structure of the gastric microbiome. To determine the impacts of host genetic variations on the gastric microbiome, six previously reported single nucleotide polymorphisms (SNPs) were examined. The minor allele of MUC1 rs4072037 was associated with an increased abundance of Ochrobactrum. The gastric microbiome altered in EC, which might be attributed in part to host genetic variations, H. pylori infection, bacterial virulence and environmental adaptations. The identified microbial signature could serve as biomarkers for clinical assessment of gastric cancer risk in high-risk patients.

Role of the Gastric Microbiome in Gastric Cancer: From Carcinogenesis to Treatment

“…However, another study showed that the bacterial diversity reduced gradually from normal, intestinal metaplasia, GC, gastritis to atrophy ( Gantuya et al, 2020 ). Moreover, microbial diversity was found to be increased in advanced-stage GC compared to the early stage, which did not differ significantly from that in chronic gastritis ( Wang L. et al, 2020 ). Novosphingobium , Ralstonia , Ochrobactrum , Anoxybacillus , and Pseudoxanthomonas were enriched in early GC whereas Burkholderia , Tsukamurella , Uruburuella , and Salinivibrio were more abundant in advanced as compared to early GC ( Wang L. et al, 2020 ).…”

“…• Signet-ring cell carcinomas were significantly enriched in the phyla Fusobacteria, Bacteroidetes, Patescibacteria, whereas in the adenocarcinoma type, Proteobacteria and Acidobacteria phyla were found advanced-stage GC compared to the early stage, which did not differ significantly from that in chronic gastritis (Wang L. et al, 2020). Novosphingobium, Ralstonia, Ochrobactrum, Anoxybacillus, and Pseudoxanthomonas were enriched in early GC whereas Burkholderia, Tsukamurella, Uruburuella, and Salinivibrio were more abundant in advanced as compared to early GC (Wang L. et al, 2020). However, another study reported that there was no significant difference in microbial community composition between early-and late-stage GC, while microbial richness decreased from normal to peritumoral to tumoral tissues (Liu et al, 2019a).…”

“…• The bacterial diversity reduced progressively from non-atrophic chronic gastritis, through intestinal metaplasia, intraepithelial neoplasia to gastric cancer Wang L. et al 2020 • 60 patients with chronic gastritis, 30 with early gastric cancer, and 30 with advanced gastric cancer…”

“…Microbial interactions determine the microbiome homeostasis and influence the disease-associated microenvironment. The reduced complexity of the microbial interaction network in GC was attributed to the lower abundance of H. pylori ( Liu et al, 2019a ; Wang L. et al, 2020 ). Other studies have suggested that the interaction network is more complex in GC, which may be the result of reduced H. pylori abundance accompanied by an increased abundance of other microorganisms ( Ferreira et al, 2018 ; Chen et al, 2019 ).…”

Overgrowth of Lactobacillus in gastric cancer

“…Recent molecular analysis reveals bacteria of the gastric microbiome are mainly from the phyla Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria, and Fusobacteria[ 9 ]. In GC, the microbiome was altered substantially[ 10 , 11 ]. Data of studies on gnotobiotic mice demonstrate that the presence of artificial microbiota in the stomach promotes the development of H. pylori induced cancer[ 12 ].…”