Can glycans and vaginal microbiota play a role in the fight against preterm birth?
A study1 exploring the interactions between vaginal microbiota and glycans of the host has revealed how these interactions influence bacterial colonization and competition between species, and with them, women's reproductive health.
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About this article
Glycans are sugar molecules located on the surface of cells and in human secretions (including cervicovaginal fluid). They are specifically recognized by antibodies, (sidenote: Lectins The term lectin (from the Latin word lectus, “chosen”) was coined by William C. Boyd and Elizabeth Shapeleigh in 1954 to refer to a heterogeneous class of (glyco)proteins, mainly of plant origin. Despite their wide range of physicochemical properties and biological activities, lectins share a common characteristic that is responsible for their various biological, biochemical, and immunochemical effects: they bind with high affinity and specificity to mono- and oligosaccharides of complex carbohydrates (including glycans) in solutions, on cell surfaces, subcellular organelles, and tissue sections. Source : Vierbuchen, M. (1991). Lectin Receptors. In: Seifert, G. (eds) Cell Receptors. Current Topics in Pathology, vol 83. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-75515-6_10 ) , and carbohydrate binding proteins. For example, in the vagina, host glycans modulate microbial colonization, acting as both binding and adhesion sites and sources of nutrients.
13.4 million An estimated 13.4 million babies were born preterm in 2020 (before 37 completed weeks of gestation).²
900,000 Preterm birth complications are the leading cause of death among children under 5 years of age, responsible for approximately 900,000 deaths in 2019.²
To better understand the interactions between these human glycans and the main pathogenic vaginal bacteria implicated in reproductive health, the researchers constructed glycan “chips” and tested the adhesion of bacteria in vitro under acidic (pH = 4) to neutral (pH = 7) conditions to reflect the reality of vaginal pH gradients observed in women.
A range of glycan-binding proteins
The results showed that the various bacteria tested could bind, to varying degrees, to several types of glycan. Moreover, according to previous work by the same team, pathogens appear to have a broader range of proteins that bind to these glycans than commensal species.
Some of the bonds are shared by different bacteria: with the exception of a few glycans, the binding profiles of the commensal bacteria Lactobacillus crispatus and L. iners and those of potentially pathogenic bacteria such as Gardnerella vaginalis and Streptococcus agalactiae overlapped, which could reflect competitive binding.
In contrast, other bonds are very specific: Fusobacterium nucleatum shows a preference for galactose-terminating glycans, while S. agalactiae is one of the few bacteria to bind to hyaluronic acid-terminating glycans.
3/4 Three-quarters of these deaths could be prevented with current, cost-effective interventions. ²
4-16% Across countries, the rate of preterm birth ranges from 4% to 16% of babies born in 2020. ²
Towards glycan-based therapies?
These results pave the way for the development of glycan-based therapies which block the adhesion of pathogens or promote colonization by probiotics. The aim is to one day reduce the incidence of bacterial vaginosis, preterm birth, and associated neonatal complications.
