image: Schematic illustration of the functional evolution and future directions of food‑medicine homologous polysaccharides. The upper panel presents four dimensions of functional reinterpretation: promotion of antigen presentation through dendritic cell maturation; regulation of immune networks and microenvironments involving macrophages, natural killer cells and regulatory T cells; modulation of the gut microbiota–immune axis via microbial fermentation and metabolite production; and integration into multifunctional immunological materials that combine bioactivity with delivery functions. The lower panel outlines four emerging directions: a shift from activity evaluation towards function‑oriented design; a transition from natural extraction towards precision molecular engineering using chemical, enzymatic or chemoenzymatic synthesis; a move from empirical development towards precision application guided by disease‑associated immune states; and a reconceptualization from bioactive constituents towards functional immunological materials that serve simultaneously as therapeutic agents and structural platforms. The figure collectively illustrates the central thesis that FMH polysaccharides should be understood as structurally programmable biological materials rather than as simple active principles.
Credit: Food & Medicine Homology, Tsinghua University Press
Precision immune modulation drives advances in vaccination, cancer immunotherapy and chronic disease care, demanding agents capable of selective immune regulation. Food‑medicine homologous (FMH) polysaccharides, valued for safety and immunomodulation, fit this requirement well. Published in Food & Medicine Homology on August 19, 2026, this Opinion re‑examines their pharmaceutical potential.
“FMH polysaccharides are more than simple bioactive compounds. Powered by unique monosaccharide composition, glycosidic linkages and 3D conformations, they can work as immune signaling molecules, structural scaffolds and cargo‑carrying delivery vehicles all at once,” said Jia‑Lun Duan, corresponding author at Nanjing University of Chinese Medicine.
Two major barriers limit progress. Natural polysaccharides suffer from intrinsic structural heterogeneity caused by source and processing variations, undermining reproducibility. Besides, pharmacological assessment and material characterization are usually performed separately, ignoring their dual identity as therapeutics and formulation components.
The team advocates an integrated strategy combining glycan structural biology, precision engineering and material design. Advanced spectroscopy, computational modeling and cryo‑imaging help decode functional structural features. Chemical, enzymatic and chemoenzymatic synthesis generates well‑defined glycan standards for mechanistic research.
These glycans exert multi‑layer functions: boosting antigen presentation as vaccine adjuvants, rebalancing immune microenvironments, and regulating immunity via the gut‑microbiota axis. Thanks to abundant reactive groups, they can self‑assemble or be modified into nanoparticles and hydrogels to co‑deliver diverse therapeutic payloads.
Critical translational hurdles remain, including batch inconsistency, uncertain immunogenicity, degradation behaviour and insufficient regulatory guidance. “Cross‑field integration of glycobiology, immunology, pharmaceutics and biomaterials will turn empirical herbal extracts into rationally built precision immune‑intervention tools,” noted Yiqun Geng, co‑corresponding author.
Other contributors are from Nanjing University of Chinese Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College and China Pharmaceutical University.
This work is supported by grants for FMH resource and immunological biomaterial research.
DOI Link:
https://doi.org/10.26599/FMH.2026.9420165
Article Title
Artificial intelligence‑driven paradigms in polysaccharide structure–activity relationships: a new revolution
Article Publication Date
19-Aug-2026