Application of microorganisms in fermented traditional Chinese medicine: A review

Microbial fermentation is an indispensable processing technology in traditional Chinese medicine (TCM). This technology uses functional microorganisms to transform bioactive components, addressing limitations of TCMs including low solubility of active ingredients, poor bioavailability and potential toxicity. Microbial fermentation preserves TCM's traditional therapeutic effects, integrates modern advantages, and thus bridges traditional TCM knowledge with current healthcare needs. However, inconsistent fermentation outcomes due to strain specificity, potential microbial contamination during scaling, and uncharacterized long-term safety of novel fermented metabolites remain non-negligible risks that require targeted mitigation.

Despite the increasing attention on microbial fermentation in TCM, existing reviews primarily focus on phenomenological descriptions (e.g., component content changes, basic fermentation effects) and lack systematic integration of molecular mechanisms, emerging fermentation strategies, and industrial application guidance, and differentiation of evidence types (in-vitro, in-vivo, human). Notably, the interaction mechanisms between microorganisms and TCM components, as well as standardized processes for fermentation scalability, remain underexplored. To address these gaps, this review updates the latest progress in microbial application in TCM, with a focus on enzyme-mediated component transformation mechanisms, structure-activity relationships of key bioactive substances (polysaccharides, flavonoids, alkaloids), optimization of fermentation processes (strains, methods, parameters), and practical applications in health food, animal husbandry, and medicine. It aims to synthesize scattered research evidence into a cohesive theoretical framework, clarify current technical bottlenecks, and provide targeted references for subsequent mechanistic exploration and industrial translation of fermented TCM.

Information relevant to the Application of Microorganisms in Fermented TCM was collected by searching the scientific databases (Google Scholar, PubMed and International Plant name Index). Botanical plant names were validated using the Plant List (www.theplantlist.org). To ensure the rigor and objectivity of this review, we established explicit inclusion and exclusion criteria for literature screening.

(1) Original research or reviews published in peer-reviewed journals; (2) Studies focusing on microbial fermentation of TCM (including single herbs, compound formulas, and TCM-derived resources); (3) Research involving clear fermentation strains, process parameters, or component-efficacy relationships; (4) Studies providing quantitative data on component changes or pharmacological effects.

(1) Conference abstracts, unpublished dissertations, or non-peer-reviewed literature; (2) Studies with unclear experimental design or incomplete data; (3) Duplicate publications or secondary analyses of existing datasets; (4) Research unrelated to microbial fermentation (e.g., chemical synthesis or physical processing of TCM). Literature screening was performed by two independent researchers, and eligible studies were cross-validated to ensure reliability.

Functional microorganisms drive transformations of TCM components during fermentation. They decompose macromolecules into absorbable small molecules, convert toxic components into low-toxic derivatives, and generate new bioactive compounds. In-vitro studies confirm these component transformations; in-vivo animal models validate enhanced efficacy and reduced toxicity; and preliminary human evidence supports potential clinical applications. These changes enhance TCM efficacy and improve safety. Fermented TCM shows broad application value in health food and medicine. However, microbe-TCM interaction mechanisms remain unclear, standardization is insufficient and microbial resources are underexplored.

Microbial fermentation optimizes TCM quality by enhancing efficacy, reducing toxicity and expanding applications, with a clear link between component changes and improved pharmacology. Future research should use multi-omics to clarify interactions, establish standardized processes and explore novel microbial resources.