Comprehensive evaluation of Ganoderma lucidum extracts: digestion kinetics, gut microbiota modulation, and immunoregulatory mechanisms.

Ganoderma lucidum (Reishi mushroom) exhibits medicinal-edible functionality mediated by bioactive components such as β-glucans and ganoderic acids that regulate immune responses through multiple pathways. However, the digestive transformation and microbiota-mediated interactions of G. lucidum extracts remain insufficiently characterized, and oral delivery results in substantial degradation during digestion, leading to limited bioavailability (<10%). The impact of extraction methods on component stability, digestive behavior, and metabolite profiles also remains unclear. To address these gaps, an in vitro gastrointestinal digestion model combined with RAW 264.7 macrophage assays and RNA sequencing was used to investigate aqueous and ethanol extract of G. lucidum. The results revealed a "digestion-metabolism-immunity" cascade influenced by extraction method, concentration, and digestion stage, with gut microbiota modulation favoring anti-inflammatory activity and increased colonic butyrate production. Immunological assessments further demonstrated suppressed inflammatory mediators and modulation of immune-related pathways, with RNA-Seq identifying key regulatory genes involved in these processes, providing insights for optimizing Ganoderma-based functional foods and advancing applications in precision nutrition.