Background: Breast-fed infants have a lower incidence of acute gastroenteritis due to the presence of several anti-infective factors in human milk. The aim of this work is to study the capacity of human milk glycosaminoglycans (GAGs) to inhibit the adhesion of some common pathogenic bacteria. Methods: GAGs were isolated from a pool of milk samples collected from different mothers during the first month of lactation. Experiments were carried out to study the ability of GAGs to inhibit the adhesion of two intestinal micro-organisms (enteropathogenic Escherichia coli serotype 0119 and Salmonella fyris) to Caco-2 and Int-407 cell lines. results: The study showed that the GAGs had an anti-adhesive effect on the two pathogenic strains studied with different degrees of inhibition. In particular, in the presence of human milk GAGs, the adhesion of S. fyris to Caco-2 cells and to Int-407 cells of both tested strains was significantly reduced. conclusion: Our results demonstrated that GAGs in human milk can be one of the important defensive factors against acute diarrheal infections in breast-fed infants.i n infancy, a wide variety of bacteria, viruses, and parasites are responsible for gastrointestinal infections. There is strong evidence to support the correlation between breastfeeding and a lower incidence of diarrhea. In fact, several anti-infective substances (secretory antibodies, lactoferrin, oligosaccharides, etc.) are present in human milk (1,2). Oligosaccharides, in particular, play several important protective, physiological, and biological roles including growth stimulation for beneficial gut microbiota and inhibition of pathogen adhesion and immunoregulation (3,4).Glycosaminoglycans (GAGs) are highly sulfated, complex, linear natural polysaccharides constituted by repeating disaccharidic units. They are generally grouped into four classes: hyaluronan, keratan sulfate, sulfated galactosaminoglycans represented by chondroitin sulfate and dermatan sulfate bearing d-galactosamine, and sulfated glucosaminoglycans with heparan sulfate and heparin having d-glucosamine. Each specific disaccharidic unit is formed of a hexosamine (galactosamine or glucosamine) residue alternated with a hexuronic acid (glucuronic or iduronic acid) with the exception of keratan sulfate containing galactose. Sulfate groups are esterified on various positions of carbohydrate backbones producing structures possessing high heterogeneous sequences and charge density (5).Contrary to oligosaccharides, GAGs are able to specifically (and aspecifically) interact with other biological components due to the presence of a great number of sulfate and carboxyl groups capable to generate highly specific sequences producing strong anionic interactions (5-7). As a consequence, it emerges that human milk GAGs could play a role as soluble receptors and would therefore have the power to inhibit the binding of different pathogens to the intestinal mucosa, thus protecting the infant from infections. Furthermore, human milk hyaluronan was recently demonstrated ...