Jing Zhang, Yang Yao
Gastric cancer (GC) remains one of the leading causes of cancer-related morbidity and mortality worldwide. Increasing evidence indicates that microbial alterations associated with GC extend beyond Helicobacter pylori (H. pylori) infection and involve coordinated ecological changes across the oral cavity, gastric mucosa, gastric fluid, and intestine. These compartment-specific microbial communities exhibit distinct compositional and functional characteristics throughout the progression from chronic gastritis and precancerous lesions of gastric cancer (PLGC) to established GC, suggesting that gastrointestinal microbial dysbiosis contributes to disease development through interactions involving mucosal barrier function, inflammation, immune regulation, and microbial metabolism. Traditional Chinese medicine (TCM) has been widely used in the prevention and treatment of GC and PLGC. Recent experimental and clinical studies suggest that certain herbal formulas and natural compounds may influence gastrointestinal microbial composition, microbial metabolites, host immune responses, and epithelial barrier function while also exhibiting anti- H. pylori, anti-inflammatory, and anti-tumor activities. This review summarizes current evidence regarding compartment-specific alterations of the oral, gastric mucosal, gastric fluid, and intestinal microbiota during gastric carcinogenesis, emphasizing the ecological heterogeneity of these microbial niches and the methodological considerations required for their interpretation. We further summarize experimental evidence demonstrating that TCM formulas and bioactive constituents regulate gastrointestinal microbiota, microbial metabolism, programmed cell death, and inflammatory signaling in models of H. pylori infection, PLGC, and GC. In addition, available randomized clinical studies investigating microbiota-related effects of TCM formulas in patients with PLGC or GC are critically reviewed.