Gut Microbiota as a Bridge: Deciphering the Mechanisms of Traditional Medicine through Microbiome-Metabolite Interactions

Traditional medicines have long been valued for their therapeutic effects across a wide range of diseases, yet the precise molecular mechanisms underlying many of their pharmacological actions remain incompletely understood. Growing evidence suggests that the gut microbiota, and the metabolites it produces or transforms, may serve as a critical intermediary linking the ingestion of traditional medicinal preparations to their systemic therapeutic effects. Components of herbal medicines are frequently modified by gut microbial enzymes into bioactive metabolites, while conversely, these preparations can reshape the composition and functional output of the gut microbiota itself, creating a bidirectional relationship that may explain therapeutic outcomes not fully accounted for by the original compounds alone.

Despite rapid growth in microbiome research, many studies linking traditional medicine to gut microbiota remain descriptive, reporting shifts in microbial composition without establishing causal mechanistic links to specific metabolites or downstream host pathways. Rigorously connecting the traditional therapeutic use of a medicinal preparation to microbiome-mediated metabolite production, and subsequently to measurable pharmacological or physiological effects, represents an important and still underexplored frontier in ethnopharmacology.

This Research Topic aims to advance the mechanistic understanding of how gut microbiota and their metabolites mediate the therapeutic effects of traditional medicines. We welcome contributions that move beyond correlative microbiome profiling to establish causal or mechanistic links between microbial metabolism of traditional medicinal preparations and their pharmacological outcomes, always with a clearly described connection to the traditional or ethnomedicinal context of the material studied.

The evidence for an impact of the gut microbiome on the specific clinical or pharmacological parameters is often at best correlative or worse, speculative effects is not substantiated. All sorts of claims are made about the impact of changes to microbiome. However, it remains unclear how this could impact on the specific pharmacological parameters. Submissions to this research topic provide the opportunity for provide better evidence and a clear pharmacological mechanism for such acclaimed effects.

We welcome contributions addressing, but not limited to, the following themes:

• Identification and characterization of gut microbiota-derived metabolites generated from traditional medicinal preparations, and their pharmacological activity

• Mechanistic studies on how traditional medicines modulate gut microbiota composition and function to achieve therapeutic effects

• Bidirectional interactions between herbal and fungal metabolites and extracts and gut microbial enzymes (e.g., biotransformation, prodrug activation, bioavailability enhancement)

• Gut microbiota-mediated mechanisms underlying the efficacy of traditional medicines in metabolic, gastrointestinal, immune, or neurological conditions

• Multi-omics approaches (metagenomics, metabolomics, and their integration) to map microbiome-metabolite-host pathways activated by traditional medicine

• Animal and in vitro models establishing causal links between microbiota-derived metabolites and the therapeutic actions of traditional preparations

• Translational and safety considerations arising from microbiota-mediated variability in individual responses to traditional medicines

• Studies assessing the potential causal links between changes to the microbiome and the acclaimed other pharmacological effects

Please note:

Contributions involving extracts derived from plants, fungi or any other organism must adhere to the Four Pillars of Best Practice in Ethnopharmacology and the ConPhyMP statement (Front. Pharmacol., 13:953205). Manuscripts must include detailed descriptions of biological material, extraction methods, and processing procedures; submissions lacking these details will be desk-rejected. The full best-practice guidance is available at: https://ga-online.org/best-practice.

Authors are encouraged to self-assess their manuscripts using the ConPhyMP tool before submission.

Studies involving animal experiments must comply with relevant institutional and national ethical guidelines and report adherence to the 3Rs principles (Replacement, Reduction, and Refinement). Studies involving human subjects must include a statement of institutional ethics committee approval.

The following types of submissions fall outside the scope of this Research Topic:

Purely in silico studies (e.g., network pharmacology, molecular docking, virtual screening) without experimental validation

Studies reporting only chemical antioxidant assays (e.g., DPPH, ABTS) without mechanistic follow-up relevant to the microbiota-mediated or pharmacological effects under investigation

Bibliometric or scientometric analyses