Structure-activity relationships and mechanisms of natural polysaccharides in modulating neurological disorders via the microbiota-gut-brain axis

Natural polysaccharides are a class of widely sourced macromolecules with low toxicity and diverse biological activities, including antioxidant, anti-inflammatory, immunomodulatory, and neuroprotective effects. The structural characteristics of polysaccharides, such as molecular weight, glycosidic bond type, and degree of branching, directly influence their biological activity. This review focuses on the structure-activity relationships between natural polysaccharides and the microbiota-gut-brain axis (MGBA). In recent years, neurological disorders have emerged as a major global health threat due to their high incidence, disability, and mortality rates. The neuroprotective effects of polysaccharides are primarily reflected in their ability to inhibit neuroinflammation, oxidative stress, and protein misfolding; maintain the integrity of the intestinal and blood-brain barrier (BBB); and regulate gut microbiota composition and neurotransmitter balance. This review aims to elucidate the mechanisms by which natural polysaccharides exert neuroprotective effects through modulation of the MGBA. Emerging evidence indicates that specific structural features of polysaccharides can mediate significant neuroprotective effects, offering potential strategies for the prevention and treatment of neurological disorders.