Gut microbiota characteristics of gastric cancer patients across distinct pathological stages and their associations with tumor and paratumor mucosal microbiota

Abstract

Gastric cancer (GC) is closely associated with microbial dysbiosis; however, the spatial–temporal characteristics of the gut, paracancerous, and intratumoral microbiomes, as well as their interrelationships during tumor progression, remain insufficiently defined. This study aimed to characterize these microbiomes in 85 GC patients from Northwest China using shotgun metagenomic sequencing and functional annotation. Clinical samples included feces, tumor tissues, and paratumor mucosal tissues (≥5 cm from the tumor margin), enabling comprehensive profiling of microbial composition at the phylum, genus, and species levels, as well as functional pathway analysis. The results showed that the microbial community was dominated by Firmicutes and Bacteroidetes (combined relative abundance >75%), maintaining structural stability across tumor stages II–IV (Stage I n=2 is only descriptively reported and excluded from formal statistical testing), thereby supporting the “core microbiota resilience” hypothesis. PERMANOVA revealed that tumor stage had a statistically significant yet modest effect on community structure (R² = 0.039, P = 0.032). MaAsLin2 identified stage-associated differential genera: Roseburia and Megamonas decreased with advancing stage, whereas Lactobacillus and Enterobacter were enriched in advanced stages (III/IV). Functional pathway analysis revealed stage-specific metabolic remodeling: Stage II was enriched in DNA repair, glycolysis, aromatic amino acid, and nucleotide biosynthesis pathways; Stage IV showed enrichment in protein deamination/demethylation, pyruvate fermentation, and coenzyme metabolism pathways. Correlation analysis further revealed a characteristic pattern of “pathogen enrichment and beneficial bacteria depletion.” Fusobacterium nucleatum and Helicobacter pylori exhibited strong positive correlations with GC, whereas short-chain fatty acid–producing bacteria such as Roseburia and Faecalibacterium prausnitzii showed significant negative correlations, particularly in paracancerous tissues. We established multi-layered taxonomic correlation profiles based on intra-cohort microbial shifts, in which Bacteroides stercoris and Bifidobacterium pseudocatenulatum exhibited the most pronounced stage-related abundance changes in the fecal microbiota across tumor stages. Overall, this study systematically delineates the structural stability, stage-specific functional remodeling, and interrelated dynamics of gut, paracancerous, and intratumoral microbiomes in gastric cancer. These findings provide descriptive baseline data of cross-compartment microbiome variation within gastric cancer patients across tumor stages, which only deliver preliminary correlative clues of GC-related microbial shifts and require further multi-cohort verification with non-cancer control populations.