Human Milk Oligosaccharides as Potential Antibiofilm Agents: A Review

Abstract

Surface-associated bacterial communities called biofilms are ubiquitous in nature. Biofilms are detrimental in medical settings due to their high tolerance to antibiotics and may alter the final pathophysiological outcome of many healthcare-related infections. Several innovative prophylactic and therapeutic strategies targeting specific mechanisms and/or pathways have been discovered and exploited in the clinic. One such emerging and original approach to dealing with biofilms is the use of human milk oligosaccharides (HMOs), which are the third most abundant solid component in human milk after lactose and lipids. HMOs are safe to consume (GRAS status) and act as prebiotics by inducing the growth and colonization of gut microbiota, in addition to strengthening the intestinal epithelial barrier, thereby protecting from pathogens. Moreover, HMOs can disrupt biofilm formation and inhibit the growth of specific microbes. In the present review, we summarize the potential of HMOs as antibacterial and antibiofilm agents and, hence, propose further investigations on using HMOs for new-age therapeutic interventions.

Keywords: antimicrobial resistance; biofilm; gut microbiota; human milk oligosaccharides.

Figure 1

Stages of biofilm formation on a biotic surface. (1) Bacteria approach the host cells and bind to specific receptor proteins. (2) After binding, bacteria start multiplying and secrets EPS that (3) eventually forms the microcolonies, and (4) the biofilm develops into a more complex 3D structure. In (5) and (6), the cycle, thus, continues with the dispersion of bacteria from the biofilm.

Figure 2

Structures of basic monosaccharide constituents of HMOs. (A) β-D-Glucopyranose, (B) β-D-Galactopyranose, (C) Sialic acid (Neuraminic acid), (D) L-Fucose, (E) N-acetylglucosamine.

Figure 3

Different types of fucosylated, neutral, and sialylated HMO molecules.

Figure 4

Galectin–HMO Binding. Human milk oligosaccharides bind to galectin expressed by intestinal epithelia; zoom-in image of gelectin-HMO binding site shows the detailed molecular representation of chemical interactions: OH groups of galactose and N-acetylglucosamine in HMOs form hydrogen bonds with amino acid residues (e.g., His44, Arg48, Trp68, Val59, Asn61, Asn46, Glu71, and Arg73) in the CRD region of galectin.

Figure 5

Anti-adhesive mechanism exhibited by HMOs where they behave as soluble decoy receptors, inhibiting bacterial adhesion to host cell surface receptors. (a) Binding of bacterial protein adhesins to the host cell surface glycan receptors, aiding successful colonization in the host system. (b) Binding of bacterial protein adhesins to HMOs thus inhibiting adhesion to host cells and successfully preventing the occurrence of infection.

Figure 6

Anti-adhesive mechanism exhibited by human milk oligosaccharides where they compete with bacterial protein adhesins for binding to host cell surface glycan receptors. (a) Binding of bacterial protein adhesins to the host cell surface glycan receptors aiding successful colonization in the host system. (b) Binding of HMOs to host cell surface receptors thus inhibiting adhesion of bacteria to host cells and successfully preventing the occurrence of infection.