Immunomodulatory Effects of Plant Polysaccharides in Chronic Inflammatory Diseases: From Innate to Adaptive Immunity

Abstract

Chronic inflammatory and autoimmune diseases—including inflammatory bowel disease, rheumatoid arthritis, asthma and metabolic inflammation—arise from a failure of immune homeostasis in which innate over-activation and dysregulated adaptive responses reinforce one another. Plant polysaccharides, structurally complex biomacromolecules from herbs, fruits and fungi, have emerged as broad-spectrum immunomodulators that act, uniquely, along the entire innate-to-adaptive continuum. Recognised as pathogen-associated-molecular-pattern (PAMP)-like ligands by pattern-recognition receptors (PRRs)—chiefly Toll-like receptor 4 (TLR4), Dectin-1, the mannose receptor and complement receptor 3—they engage MyD88–NF-κB, Syk–Card9 and MAPK signalling to shape macrophage polarisation, dendritic-cell maturation and natural-killer-cell activity. Through dendritic-cell bridging they then direct the adaptive response, rebalancing the Th1/Th2, Th17/Treg and effector/regulatory axes whose distortion drives chronic inflammation. A third, indirect route operates through the gut microbiota: non-digestible polysaccharides are fermented to short-chain fatty acids that promote regulatory T-cell differentiation and epithelial-barrier integrity.
This review synthesises these mechanisms, emphasising the structure–activity relationships—molecular weight, backbone linkage, branching and conformation—that govern potency, and the context-dependent, bidirectional nature of polysaccharide immunomodulation. Compiled preclinical data show 45–88% shifts in pro- versus anti-inflammatory mediators, restoration of Th17/Treg balance, and 45–62% reductions in disease-severity markers across models of chronic inflammation. The review concludes that plant polysaccharides are versatile homeostatic immunomodulators whose translation now depends on structural standardisation, resolution of oral-bioavailability limitations, and rigorous clinical validation.