Oligosaccharides, Gut Microbiota, and Mucosal Health: Molecular Mechanisms and Implications for Early-Life Gut Health
- 1Department of Biosciences, Biotechnology and Environment, University of Bari Aldo Moro, 70125 Bari, Italy
- 2Pediatric Unit, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari Aldo Moro, 70124 Bari, Italy
Abstract
Oligosaccharides are structurally diverse glycans that influence intestinal homeostasis through mechanisms extending beyond conventional prebiotic activity. This review examines how dietary, human milk, host-derived, and biotechnologically produced oligosaccharides modulate the gut microbiota and mucosal host–microbe interactions, with particular attention to pediatric health. Non-digestible oligosaccharides support saccharolytic microbial communities, cross-feeding networks, and short-chain fatty acid production, thereby affecting luminal pH, epithelial metabolism, mucus production, barrier integrity, and immune signaling. Their biological effects are strongly determined by monosaccharide composition, linkage configuration, branching, charge, degree of polymerization, terminal residues, and spatial presentation. Neutral human milk oligosaccharides and galacto-oligosaccharides may reduce pathogen colonization by mimicking host glycans, occupying adhesin-binding sites, modifying epithelial glycosylation, and limiting biofilm initiation. Selected chitooligosaccharides can exert direct antibacterial effects through charge-dependent interactions with bacterial envelopes, although these effects depend on molecular size, charge, and chemical derivatization. In addition, the α1,4-GlcNAc-terminated O-glycan motif of gastric MUC6 provides a distinct example of host-associated glycan-mediated inhibition of bacterial metabolism. During infancy, human milk oligosaccharides promote a Bifidobacterium-enriched microbiota and may contribute to intestinal and immune maturation. Galacto- and fructo-oligosaccharide-supplemented formulas reproduce some microbiota- and metabolite-related effects, although evidence for preventing infectious, allergic, or inflammatory disease remains inconsistent. Experimental findings also suggest a role in recovery from antibiotic-associated dysbiosis, but clinical evidence is limited by heterogeneous populations, exposures, formulations, and endpoints. Future studies should use structurally defined compounds, mechanism-specific assays, and clinically relevant outcomes to establish causal structure–function relationships and identify pediatric populations most likely to benefit.
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BibTeX
@article{mentino2026oligosaccharides,
title = {{Oligosaccharides, Gut Microbiota, and Mucosal Health: Molecular Mechanisms and Implications for Early-Life Gut Health}},
author = {Donatella Mentino and Giovanni Scillitani and Daniela Semeraro and Marco Vito Guglielmi and Nastasia Taldone and Michelle Laterza and Rossella Vitale and Maria Felicia Faienza and Maria Mastrodonato},
journal = {Nutrients},
year = {2026},
month = oct,
doi = {10.3390/nu18203369},
url = {https://www.mdpi.com/2072-6643/18/20/3369},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Oligosaccharides, Gut Microbiota, and Mucosal Health: Molecular Mechanisms and Implications for Early-Life Gut Health
AU - Donatella Mentino
AU - Giovanni Scillitani
AU - Daniela Semeraro
AU - Marco Vito Guglielmi
AU - Nastasia Taldone
AU - Michelle Laterza
AU - Rossella Vitale
AU - Maria Felicia Faienza
AU - Maria Mastrodonato
PY - 2026
DA - 2026/10/01
JO - Nutrients
DO - 10.3390/nu18203369
UR - https://www.mdpi.com/2072-6643/18/20/3369
AB - Oligosaccharides are structurally diverse glycans that influence intestinal homeostasis through mechanisms extending beyond conventional prebiotic activity. This review examines how dietary, human milk, host-derived, and biotechnologically produced oligosaccharides modulate the gut microbiota and mucosal host–microbe interactions, with particular attention to pediatric health. Non-digestible oligosaccharides support saccharolytic microbial communities, cross-feeding networks, and short-chain fatty acid production, thereby affecting luminal pH, epithelial metabolism, mucus production, barrier integrity, and immune signaling. Their biological effects are strongly determined by monosaccharide composition, linkage configuration, branching, charge, degree of polymerization, terminal residues, and spatial presentation. Neutral human milk oligosaccharides and galacto-oligosaccharides may reduce pathogen colonization by mimicking host glycans, occupying adhesin-binding sites, modifying epithelial glycosylation, and limiting biofilm initiation. Selected chitooligosaccharides can exert direct antibacterial effects through charge-dependent interactions with bacterial envelopes, although these effects depend on molecular size, charge, and chemical derivatization. In addition, the α1,4-GlcNAc-terminated O-glycan motif of gastric MUC6 provides a distinct example of host-associated glycan-mediated inhibition of bacterial metabolism. During infancy, human milk oligosaccharides promote a Bifidobacterium-enriched microbiota and may contribute to intestinal and immune maturation. Galacto- and fructo-oligosaccharide-supplemented formulas reproduce some microbiota- and metabolite-related effects, although evidence for preventing infectious, allergic, or inflammatory disease remains inconsistent. Experimental findings also suggest a role in recovery from antibiotic-associated dysbiosis, but clinical evidence is limited by heterogeneous populations, exposures, formulations, and endpoints. Future studies should use structurally defined compounds, mechanism-specific assays, and clinically relevant outcomes to establish causal structure–function relationships and identify pediatric populations most likely to benefit.
SN - 2072-6643
ER -