Lactobacillus dominance and associated biomolecules in Kenyan adolescent girls and young women around sexual debut
Date
2022-01-28
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Abstract
A healthy vaginal microbiome is characterized by low species diversity and Lactobacillus dominance (LD). LD is associated with a low vaginal pH that protects against sexually transmitted infections. LD is established during puberty, but is lost in many women during their reproductive years, especially those of African descent. Glycogen is thought to be a key host- derived nutrient that supports vaginal lactobacilli and their fermentative production of lactic acid, but this mechanism remains incompletely understood. Some vaginal Lactobacillus species and strains have been shown to directly utilize glycogen in vitro by secreting glycogen-degrading pullulanase enzymes, but the prevalence and activity of these genes in vivo is unknown. To establish methods for assessing relationships amongst microbes and biomolecules involved in glycogen utilization, an exploratory pilot study (N=17) of a cohort of young women (age 16–20 yrs) recruited in Thika, Kenya was assessed (Chapter II). The results of our cohort study showed that although most low-risk African women retained dominant L. crispatus into their teenage years, 36% were dominated by L. crispatus strains encoding functionally inactive pullulanase. These samples contained 66% lower pullulanase activity and 40% lower lactic acid levels, which future studies will investigate as potential risk factors for LD loss and poorer vaginal health. The second major objective of this thesis was to investigate glycogen utilization by vaginal lactobacilli in culture in order to better define the fermentation capacity of prevalent vaginal Lactobacillus species (Chapter III). My results showed that L. crispatus can ferment more carbohydrate nutrients than L. iners and has a unique ability to utilize glycogen as a primary nutrient source. Surprisingly, however, I also demonstrated that L. crispatus’ glycogen degradation phenotype could be depleted or lost under maltose-based cultivation conditions. Glycogen-derived nutrients were utilized by L. crispatus and L. jensenii and was coupled with these species’ ability to lower culture pH. In contrast, L. iners displayed restricted fermentation and correspondingly a higher pH. These experiments informed our understanding of how these remarkable microbes establish dominance within the vaginal niche, improving experimental practices and helping to revolutionize L. crispatus biotherapeutics that promote women’s health.
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Keywords
Lactobacillus, bacterial vaginosis, vaginal microbiome, sexual debut, HIV, pullulanase
Citation
Cochinamogulos, A. A. (2022). Lactobacillus dominance and associated biomolecules in Kenyan adolescent girls and young women around sexual debut (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.