Abstract
Background: Globally, gastric cancer is the third most common cancer and the third leading cause of cancer death. Proximal and distal gastric cancers have distinct clinical and biological behaviors. The microbial composition and metabolic differences in proximal and distal gastric cancers have not been fully studied and discussed. Methods: In this study, the gastric microbiome of 13 proximal gastric cancer tissues, 16 distal gastric cancer tissues, and their matched non-tumor tissues were characterized using 16S rRNA amplicon sequencing. Additionally, 10 proximal gastric cancer tissues, 11 distal gastric cancer tissues, and their matched non-tumor tissues were assessed by untargeted metabolomics. Results: There was no significant difference in microbial diversity and richness between the proximal and distal gastric cancer tissues. At the genus level, the abundance of Rikenellaceae_RC9_gut_group, Porphyromonas, Catonella, Proteus, Oribacterium, and Moraxella were significantly increased in Proximal T, whereas that of Methylobacterium_Methylorubrum was significantly increased in Distal T. The untargeted metabolomics analysis revealed 30 discriminative metabolites between Distal T and Distal N. In contrast, there were only 4 discriminative metabolites between Proximal T and Proximal N. In distal gastric cancer, different metabolites were scattered through multiple pathway, including the sphingolipid signaling pathway, arginine biosynthesis, protein digestion and absorption, alanine, aspartate and, glutamate metabolism, etc.In proximal gastric cancer, differential microbial metabolites were mainly related to hormone metabolism. Conclusion: Methylobacterium-Methylorubrum was significantly increased in Distal T, positively correlated with cancer-promoting metabolites, and negatively correlated with cancer-inhibiting metabolites. Rikenellaceae_RC_gut_group was significantly increased in Proximal T and positively correlated with cancer-promoting metabolites. Further studies regarding the functions of the above-mentioned microorganisms and metabolites were warranted as the results may reveal the different mechanisms underlying the occurrence and development of proximal and distal gastric cancers and provide a basis for future treatments. Importance: First, the differences in microbial composition and metabolites between the proximal and distal gastric cancers were described; then, the correlation between microbiota and metabolites was preliminarily discussed. These microbes and metabolites deserve further investigations as they may reveal the different mechanisms involved in the occurrence and development of proximal and distal gastric cancers and provide a basis for future treatments.