Abstract
Objective
Chemotherapy-induced toxicities represent a major clinical challenge in gastric cancer treatment, with limited effective management strategies. Emerging evidence suggests that gut microbiota dysbiosis is a key driver of these adverse effects, while traditional Chinese medicine (TCM) shows potential in modulating gut microbial composition. This review aims to systematically summarize the molecular mechanisms and clinical evidence of TCM in alleviating chemotherapy-induced toxicities in gastric cancer through gut microbiota regulation and to identify current research gaps.Methods
A systematic literature search was conducted using SCI-indexed studies, primarily published in recent years, with inclusion of foundational studies where necessary. The review focused on chemotherapy-induced gut microbiota dysbiosis and its role in toxicity, as well as the effects of TCM-including polysaccharides, flavonoids, and herbal formulations-on microbial composition, metabolic products such as short-chain fatty acids (SCFA), LPS, and inflammatory signaling pathways.Results
Gut microbiota dysbiosis contributes to systemic inflammation primarily through activation of the LPS/TLR4/NF-κB/NLRP3 inflammasome pathway and reduced SCFA-mediated histone deacetylase inhibition. TCM regulates gut microbiota through a "structure-metabolite-immune" framework, restoring microbial diversity, increasing SCFA production, reducing LPS levels, and suppressing inflammatory signaling. Clinically, oral and injectable TCM formulations such as SFI and HCS have shown moderate- to high-quality evidence in improving immune function, alleviating myelosuppression, and reducing gastrointestinal toxicities, whereas evidence for external therapies remains limited.Conclusion
TCM represents a promising microbiota-targeted strategy for mitigating chemotherapy-induced toxicities in gastric cancer. Future studies should focus on STING signaling and the gut-brain axis, conduct large-scale randomized controlled trials (RCTs), and develop microbiota-based personalized TCM interventions to advance evidence-based integrative oncology.