Structural heterogeneity, processing transformation, and gut microbiota-related immunomodulation of Glycyrrhiza...

Glycyrrhiza polysaccharides (GPS) are bioactive macromolecules isolated from plants of the genus Glycyrrhiza. However, the term GPS is used across the literature to describe chemically and structurally non-equivalent materials, including crude polysaccharide extracts, purified fractions, processing-modified products, and low-molecular-weight fragments. Differences in purification level and structural heterogeneity hinder cross-study comparisons and mechanistic synthesis. Research has consequently expanded beyond extraction optimization and activity screening of crude extracts to address source-dependent variation, structural features, processing-induced transformation, in vivo fate, intestinal utilization, and gut microbiota-mediated immunomodulation. Available evidence indicates that GPS composition and physicochemical properties are strongly influenced by species, geographical origin, plant part, and processing method. Following oral administration, GPS is largely retained and utilized in the intestine. Several structurally characterized low-molecular-weight neutral fractions have been reported to remodel the gut microbiota, increase short-chain fatty acid production, strengthen the intestinal epithelial barrier, and ameliorate immune dysregulation. This review synthesizes current knowledge of GPS sources and structures, processing-induced transformation and molecular-weight reduction, intestinal utilization, microbiota-mediated immunomodulation, and quality evaluation. We also examine unresolved controversies, methodological limitations, minimum reporting requirements, and barriers to translation. By organizing the evidence within a structure-processing-intestinal utilization-immunity framework, this review aims to move GPS research beyond descriptive activity screening toward structurally defined, mechanism-based, and translationally relevant studies.