Glycobiology: Promising Future For Cutting Edge Microbiome Applications

Dr. Philippe Ulsemer, Acaryon UG, Schildow, Germany

Carbohydrates are major components of the surface of microbial and mammalian cells. On mammalians cells, they are mainly found covalently bound to proteins and lipids (glycosylations). On microbial cells, they are found as glycosylations and as polysaccharides physically attached to the cell wall (peptidoglycan, lipopolysaccharides, capsular polysaccharides). Additionally, polysaccharides are released into the environment (exopolysaccharides).

Unlike nucleic acids and proteins, carbohydrate structures are assembled without the use of a template, they can be highly branched and their composition can be influenced by environmental factors. Consequently, carbohydrate structures present a high degree of diversity allowing cell-specific, strain-specific, microenvironment-specific (i.e. stress, inflammation) and state-specific (i.e. undifferentiated vs. differentiated, health vs. disease) structures.

Due to their location on the cell surface and their specificity, carbohydrate structures play fundamental roles in interaction and communication between microorganisms and between host and microorganisms. Thus, microbial carbohydrates may have prebiotic or antimicrobial properties, and may be involved in cell-cell recognition, receptor activation, signal transduction and immune system regulation. On the surface of host cells, carbohydrates are known to be receptors or co-receptors for specific microbial binding, being responsible for specificity and tropism of commensal and pathogenic bacteria.

The fundamental role played by microbial carbohydrate structures and microbial carbohydrate-binding moieties in many biological processes opens tremendous opportunities for the development of next generation microbiome products (pre-, pro- and postbiotics as well as pharmaceutical microbiome applications) with potential application in a wide range of fields including infection, cancer, allergy, chronic diseases and auto-immune diseases.

Two bacterial strains naturally expressing carbohydrate structures with cancer and infection preventive properties respectively illustrate the potential of microbial glycobiology for the development of cutting-edge microbiome applications.

The strain Bacteroides xylanisolvens DSM 23964 naturally expresses a carbohydrate structure immunologically similar to the human carbohydrate-cancer antigen TF-a (Thomsen-Friedenreich). The oral administration of this strain was demonstrated to induce the production of TF-specific antibodies that are considered to have cancer prevention properties. The strain Lactobacillus paracaseii K15 naturally expresses a carbohydrate structure specifically binding the cholera toxin. This strain may be developed as a toxin-neutralization product specifically used to prevent the development of Vibrio cholerae and ETEC infections.

Based on our technology platform we screen the microbiome (gut, skin, mucosa) for microorganisms expressing specific carbohydrate structure(s) on their surface and further develop them as next generation pro- and postbiotic products dedicated to benefit human and animal health.

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