Young Adults with Gastric Cancer Experience Progressive Taxonomic Loss and Broad Functional Decline in the Gastric Mucosal Microbiome

Abstract

Gastric cancer is a progressive malignancy influenced by genetic and environmental factors, with age being a well-established risk factor. Additionally, emerging evidence suggests alterations in the gastric mucosal microbiome are linked to gastric carcinogenesis, however, the effect of age on microbial dynamics remains unexplored. This study investigates whether age influences gastric microbiome composition and function across different stages of gastric cancer progression. Using a 16S rRNA dataset of 310 patients from Northern China stratified by gastric cancer stage and age, alpha and beta diversity metrics, core microbiome, indicator species, and predictive functional pathways were analyzed. No significant differences were observed for alpha and beta diversity with age for each cancer stage. Core microbiome analysis indicated that older patients shared a similar core microbiome across different cancer stages, whereas younger patients lost their unique taxonomic profile with disease progression. In contrast with older patients, younger gastric cancer patients also experienced broad suppression of metabolic functional capacity indicated by the downregulation of biosynthetic and energy-producing pathways and the upregulation of the L-1,2-propanediol degradation pathway. Despite minor taxonomic differences, our study provides evidence of broad functional changes in the gastric microbiome that may promote reduced resilience to gastric cancer progression in younger gastric cancer patients. Overall, our findings suggest that age may not significantly influence gastric microbiome dynamics during gastric carcinogenesis. However, younger patients may be more susceptible to adverse alterations in microbial community structure and function, indicating the need for a more nuanced view of the effects of age on the gastric microbiome.