Metabolic conversion of dioscin-diosgenin and their interactions with gut microbiota: recent advances

HMF plants are rich sources of steroidal saponins, and dioscin and diosgenin are the widely distributed and bioactive compounds. Despite their poor oral bioavailability, these saponins undergo extensive microbial transformation, yielding bioavailable metabolites with enhanced lipophilicity and pharmacological potential. Recent studies indicate that the interaction between diosgenin and the gut microbiota plays a crucial role in regulating metabolic, immune, and neuroendocrine functions. Understanding this bidirectional relationship may provide a foundation for developing novel microbiota-targeted nutritional and therapeutic strategies.

The purpose of this review was to summarize current research progress on the biotransformation, biological functions, and health implications of diosgenin and its precursors. We elucidate how microbial metabolism modulates diosgenin activity and how diosgenin reshapes gut microbial composition and function to maintain intestinal homeostasis.

A comprehensive literature search was conducted using four major electronic databases, including PubMed, Web of Science, Embase, and CNKI, were searched from inception to January 2026. Key words used in the literature search were "diosgenin", "dioscin", "steroidal saponins", "gut microbiota", "homology of medicine and food", "β-glucosidase", "microbial transformation", "mucosal immunity", "metabolic and inflammatory disorders" and "gut brain axis". Keywords are linked with AND/OR. Chemical structure data and biotransformation pathways were confirmed through peer-reviewed sources and authoritative databases such as NIH and PubChem.

Evidence indicates that intestinal microbial β-glucosidases catalyze the deglycosylation of dioscin into lipophilic aglycone diosgenin, thereby enhancing its membrane permeability and bioactivity. Diosgenin selectively enriches beneficial microbial populations and promotes the production of key microbial metabolites, including SCFAs and tryptophan-derived indoles. These microbial metabolites play pivotal roles in intestinal epithelial integrity and mucosal immune homeostasis. They modulate the Treg balance by activating key host signaling pathways. The primary receptors involved include GPRs, AHR, and PPARs. Preclinical studies strongly support the therapeutic potential of the microbiota-diosgenin axis in alleviating T2D, NAFLD, IBD, neuroinflammation, and age-related pathologies.

This review highlights the gut microbiota as an important modulator of diosgenin bioavailability and biological activity, based largely on preclinical evidence. Differences in microbial composition and metabolic capacity may contribute to interindividual variability in host responses to diosgenin. In this context, we propose the concept of diosgenin metabotypes as a conceptual framework to describe microbiota-dependent differences in diosgenin metabolism, which may inform future microbiome-guided nutritional and therapeutic strategies.