Applications of traditional Chinese medicine in cancer immunotherapy via gut microbiota modulation: Current status, mechanisms, challenges and perspectives

Nov 8, 2025Pharmacological research

Using Traditional Chinese Medicine to Support Cancer Immunotherapy by Changing Gut Bacteria: Current Knowledge, How It Works, Challenges, and Future Directions

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Abstract

Traditional Chinese medicine (TCM) may modulate gut microbiota to enhance cancer immunotherapy.

The gut microbiota plays a crucial role in regulating antitumor immunity through its impact on the tumor immune microenvironment.
TCM is associated with multi-target systemic regulation that fortifies immune homeostasis and promotes immune clearance.
TCM can influence the production of microbial metabolites, which may reprogram the tumor immune microenvironment by enhancing immune cell infiltration.
Bioactive TCM components and classical formulas are linked to reshaping microbial communities and enriching beneficial bacteria.
Despite promising preclinical findings, challenges such as mechanistic complexity and lack of standardization limit clinical translation of these strategies.
Integrating multi-omics approaches and intelligent screening of herbal compounds may provide potential solutions to enhance the efficacy of cancer immunotherapy.

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Cancer immunotherapy faces significant limitations due to therapeutic resistance. Emerging evidences have identified the gut microbiota (GM) as a crucial regulator of antitumor immunity through its effects on the tumor immune microenvironment (TIME). Guided by the principle of "fu zheng qu xie" (fortifying healthy qi to reinforce immune homeostasis and eliminating pathogenic factors to promote immune clearance), traditional Chinese medicine (TCM) exerts multi-target systemic regulation. Specifically, TCM modulates gut microecology, which in turn regulates the production of microbial metabolites (e.g., short-chain fatty acids, bile acids), ultimately reprogramming TIME by enhancing immune cell infiltration into the tumor parenchyma, optimizing T-cell cytotoxicity and differentiation, improving antigen presentation, and alleviating immunosuppression. This review systematically summarizes the causal chain of "TCMGMmetabolitesimmune cellsTIME" across different immune phenotypes, emphasizing how bioactive TCM components and classical formulas reshape microbial communities, enrich beneficial bacteria, and regulate metabolic pathways to potentiate cancer immunotherapy. Despite promising preclinical data, challenges persist due to mechanistic complexity, the lack of standardization, and limited clinical translation. Potential solutions include multi-omics integration, intelligent screening of herbal compounds, and targeted delivery systems. With advancing pharmacological insights, TCM-derived microbiome modulators (TMMs), defined as phytochemicals and formulations that systematically modulate gut microecology, may overcome immunotherapy resistance, representing a novel strategy for enhancing cancer immunotherapy.

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Applications of traditional Chinese medicine in cancer immunotherapy via gut microbiota modulation: Current status, mechanisms, challenges and perspectives

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