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The Role of Oligosaccharides in Host-Microbial Interactions for Human Health

Ross, Sarah A. BSc; Lane, Jonathan A. PhD; Marotta, Mariarosaria PhD; Kavanaugh, Devon PhD; Ryan, Joseph Thomas PhD; Joshi, Lokesh PhD; Hickey, Rita M. PhD

doi: 10.1097/MCG.0000000000000694

Milk oligosaccharides have many associated bioactivities which can contribute to human health and offer protective properties to the host. Such bioactivities include anti-infective properties whereby oligosaccharides interact with bacterial cells and prevent adhesion to the host and subsequent colonization. Milk oligosaccharides have also been shown to alter the glycosylation of intestinal cells, leading to a reduction in pathogenic colonization. In addition, these sugars promote adhesion of commensal bacterial strains to host cells as well as possessing the ability to alter mucin expression in intestinal cells and improve barrier function. The ability of milk oligosaccharides to alter the transcriptome of both commensal bacterial strains and intestinal epithelial cells has also been revealed, indicating the potential of many cell types to detect the presence of milk oligosaccharides and respond accordingly at the genetic level. Interestingly, domestic animal milk may provide a bioactive source of oligosaccharides for formula supplementation with the aim of emulating the gold standard that is human milk. Overall, this review highlights the ability of milk oligosaccharides to promote health in a variety of ways, for example, through direct bacterial interactions, immunomodulatory activities, promotion of gut barrier function, and induction of protective transcriptional responses.

*Teagasc Food Research Centre, Moorepark Co., Cork

National Centre for Biomedical Engineering Science, National University of Ireland Galway, Galway, Ireland

Supported by the Department of Agriculture and Food, Ireland, under the Food Institutional Research Measure, project reference number 10/RD/TMFRC/708.

S.A.R. is in receipt of a Teagasc Walsh Fellowship. The remaining authors declare that they have nothing to disclose.

Address correspondence to: Rita M. Hickey, PhD, Teagasc Food Research Centre, Moorepark Co., Cork, P61 C996, Ireland (e-mail:

Oligosaccharides, including those found in milk have the capacity to interact with both host and bacterial cell surfaces which in turn offers the host protection from pathogenic infection. There is evidence to suggest that the protection afforded to the host is not as a consequence of a single oligosaccharide activity but rather can be attributed to the many health promoting activities associated with milk oligosaccharides. For example, human milk oligosaccharides have been demonstrated to bind directly to invading pathogens, preventing host cell attachment and subsequent colonization of gastrointestinal epithelial cells.1 Interestingly, oligosaccharides found in milk have been shown to have the potential to reduce the threat of infection in other organs by directly interacting with the bacteria. For instance, the ability of the oligosaccharide 6′-siallylactose to reduce the adhesion2 and invasion3 of Psudomonas aeruginosa to lung cells has been demonstrated in vitro. Milk oligosaccharides have also been shown to promote the adhesion of commensal bacteria to host receptors,4 which can also aid in the prevention of pathogenic establishment in the host. More recently, the immune-modulatory properties of bioavailable milk oligosaccharides and their capacity to change host cell surface glycosylation have been identified.5 The ability of oligosaccharides to modulate cell surface glycosylation lead to a reduction in the adhesion of enteropathogenic Escherichia coli to host cells in vitro, further highlighting the protective capabilities of milk glycans. Human intestinal epithelial cells are coated in a protective mucin layer which acts as a barrier to pathogens.6 Oligosaccharides were also shown to have potential in altering mucin expression which may improve the protection these secretory proteins offer. For example, commercial oligosaccharides such as galactooligosaccharides have been shown to enhance the expression of mucin-associated proteins including mucin 2, potentially promoting mucosal barrier function and conferring further resistance to pathogen infection.7

Milk oligosaccharides were shown to modulate the transcriptomic response of gastrointestinal commensal bacteria such as the prototypical infant bifidobacterial strain, Bifidobacterium longum subsp. infantis.4 In this particular study, the authors highlighted the ability of the bifidobacterial strain to sense the presence of milk oligosaccharides and mount a transcriptomic response leading to an increased colonization potential of the bacterial species to a human colonic epithelial HT-29 cell line. Interestingly, many genes potentially involved in the adhesion process were seen to be upregulated after exposure to milk oligosaccharides. In addition to impacting the transcriptomic response of commensal bacteria, milk oligosaccharides from bovine and human milk have been shown to affect the transcriptional response of a human colonic epithelial HT-29 cell line.8 In this study, genes involved in the immune system, including cell surface receptors, interleukins and chemokines, were shown to be differentially regulated in response to oligosaccharides from both bovine and human colostrum, suggesting a possible role in protecting the susceptible neonatal gut from pathogenic infection. Interestingly, this study highlights the potential for bovine milk oligosaccharides to elicit a transcriptional immunologic response similar to that observed for human milk oligosaccharides. This study highlights the potential of bovine milk as a potential source of oligosaccharides for use in infant formula where an important objective is to bridge the “oligosaccharide gap” which is evident between human breast milk and infant formula. Indeed, it is known that breast fed infants are less susceptible to pathogenic associated diarrhea9,10 and achieve a higher cognitive and developmental score11,12 when compared with formula fed infants. Thus, it is clear that bovine milk may be an attractive source of milk oligosaccharides for formula supplementation in an effort to emulate the gold standard that is human milk.

Overall it can be seen that oligosaccharides, including those found in human and domestic animal milks as well as enzymatically produced oligosaccharides such as galactooligosaccharide, possess the capabilities to protect from pathogenic infection and in some cases increase commensal colonization through many different health promoting activities. The studies mentioned above have demonstrated the important roles oligosaccharides may play in maintaining the balance between reducing pathogenic infections and increasing commensal colonization potential. Such health promoting activities are modulated through direct bacterial interactions, immunomodulatory activities, promotion of gut barrier function, and induction of protective transcriptional responses.

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milk oligosaccharides; anti-infective; bioactivities; transcriptome

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