The Gut Microbiome's Impact on the Pathogenesis and Treatment of Gastric Cancer-An Updated Literature Review

Abstract

The gut microbiota plays a critical role in maintaining gastrointestinal homeostasis, immune regulation, and metabolic processes. Recent evidence has highlighted its significant influence on gastric carcinogenesis. Helicobacter pylori, a well-established class I carcinogen, remains the most prominent microbial risk factor for gastric cancer. However, emerging studies indicate that alterations in the broader gastric and intestinal microbial communities, referred to as dysbiosis, may also contribute to tumor initiation, progression, and immune evasion. These microbial shifts can lead to chronic inflammation, genotoxic metabolite production, and modulation of signaling pathways such as NF-κB and Wnt/β-catenin. This review explores the current understanding of the gut microbiome's contribution to gastric cancer pathogenesis, including microbial signatures associated with precancerous lesions and the tumor microenvironment. Furthermore, the potential of microbiota-based biomarkers and therapeutic interventions, including probiotics, prebiotics, and fecal microbiota transplantation, is discussed as part of emerging precision medicine strategies.

Keywords: Helicobacter pylori; carcinogenesis; gastric cancer; gut microbiome; microbial biomarkers; microbiome-targeted therapy.

Figure 1

Microbial dysbiosis-driven carcinogenic mechanisms in the gut [24]. AP-1, activator protein-1; APC, adenomatous polyposis coli; BAs, bile acids; CRC, colorectal cancer; CYP7A1, cholesterol 7 α hydroxylase; EGFR, epidermal growth factor receptor; ERK1/2, extracellular signal-regulated kinase 1/2; FMO, flavin monooxygenase; GSK3β, glycogen synthase kinase 3β; H2S, hydrogen sulfide; IL-1β, interleukin-1β; IL-23, interleukin-23; LEF, lymphatic enhancement factor; LPS, lipopolysaccharide; NF-κB, factor-Kappa B; NOCs, N-nitroso compounds; p38 MAPK, p38 mitogen-activated protein kinase; PAMPs, pathogen-associated molecular patterns; PKC, protein kinase C; ROS, reactive oxygen species; TCF, T-cell factor; TJ, tight junctions; TLR, Toll-like receptor; TMA, trimethylamine; TMAO, trimethylamine-N-oxide; TNF-α, tumor necrosis factor-α.