Nature-inspired oligosaccharides: plant and algal routes to human milk functionality

Human milk oligosaccharides (HMO) shape early-life health by guiding microbiome assembly, fortifying the mucosal barrier, calibrating immune responses by enhancing secretory IgA at mucosal surfaces, blocking pathogen adhesion, and influencing the microbiota-gut-brain axis. Direct deployment of structurally diverse HMO at population scale remains constrained by manufacturing complexity and cost. This review examines "nature-inspired" oligosaccharides derived from plant and marine algal as affordable, scalable HMO mimetics, mapping chemistry to biology across five functional domains: microbiota architecture & metabolism, inhibition of pathogen adhesion via glycan decoy mechanisms, immune education, mucosal barrier enhancement and gut-brain regulation. We synthesize and critically appraise evidence on plant-derived fructo-, xylo-, and mannan-oligosaccharides, as well as on red-algal agaro-oligosaccharides and brown-algal fuco-oligosaccharides. Although these glycans do not fully replicate individual HMO structures, they can exhibit convergent mechanisms: selective fueling of saccharolytic consortia to produce functional metabolites (SCFAs), multivalent fucose-rich decoying of viral/bacterial adhesins, dendritic-cell/T- and B-cell tuning, epithelial junction and mucus programs, and neuroactive/metabolite signaling along the gut-brain axis. Framed as functional mimicry rather than strict structural emulation, plant and marine oligosaccharides emerge as promising "glycobiotics" to deliver HMO-like benefits across the lifespan, with opportunities for precision, personalized, and sustainable formulations guided by multi-omics and glycoinformatics.