The Central Qi theory in traditional Chinese medicine: Gut microbiota modulation as a strategic target for hepatocellular carcinoma therapy.

ETHNOPHARMACOLOGICAL RELEVANCE: Patients with intermediate and advanced hepatocellular carcinoma (HCC) often derive limited benefit from systemic therapy and experience a substantial symptom burden with deterioration in quality of life. These challenges underscore the need for safe, effective adjunctive or alternative therapies. The traditional Chinese medicine concept of Central Qi shows conceptual contemporary with contemporary understanding of the gut-liver axis and microbiome biology. Chinese herbal medicines centered on tonifying the central and replenishing qi (Buzhong Yiqi) are considered adjunctive or alternative therapeutic options for alleviating symptoms, improving quality of life, and enhancing tolerance and adherence to standard treatments.

AIM OF THIS REVIEW: To delineate links among the interrelations among Central Qi, the gut microbiota, and HCC, to synthesize evidence on how Buzhong Yiqi medicines modulate the gut microbiota, and to elucidate the proposed mechanistic bases for their potential adjunctive effects in HCC. This review aims to provide a biologically plausible framework to inform microbiome-based mechanistic research and clinical translation.

METHODS

Databases including PubMed, Web of Science, Elsevier ScienceDirect, CNKI, and Google Scholar were searched using predefined terms related to hepatocellular carcinoma, gut microbiota, and the gut-liver axis, nutrient absorption, metabolic regulation, immune modulation, and Buzhong Yiqi medicines, as well as their representative herbs. In vivo, in vitro, and clinical studies published from 2000 to October 2025 were included.

RESULTS

Dysbiosis disrupts the metabolic pathways of bile acid, short-chain fatty acid, and tryptophan metabolic pathways, while compromising the intestinal barrier. This disruption can worsen appetite regulation and energy imbalance, as well as weaken antitumor immunity. Buzhong Yiqi medicines have been reported to enrich beneficial taxa, reduce pathogens and pathobionts, and improve microbial metabolite profiles, restoration of barrier integrity, improvements in nutrient intake and energy homeostasis. These findings are heterogeneous and largely derived from non-HCC models, but collectively suggest potential support of metabolic and immune homeostasis, with possible influence on the tumor immune microenvironment. Early exploratory data also indicate a potential interaction with immune checkpoint inhibitors, although its clinical significance remains uncertain.

CONCLUSION

Central Qi deficiency provides a biologically plausible conceptual framework linking impaired digestion, disrupted energy metabolism, microbial dysbiosis, and reduced immune responsiveness in HCC. Modulation of the GM through Buzhong Yiqi medicines may offer supportive metabolic and immunological benefits, but current evidence is preliminary, based mainly on associative findings, and requires cautious interpretation. Key uncertainties remain regarding causal relationships, HCC-specific mechanisms, and the consistency of clinical effects. Future research should prioritize standardized preparations, mechanistic validation, biomarker-guided stratification, and rigorously designed clinical trials to clarify the clinical relevance of these proposed pathways and to advance global acceptance of integrative therapy.