#85: Nutrient Availability Drives Community Dynamics in the Vaginal Microbiota

Abstract

Background Nutrient utilization is both critical for niche occupation and is the driver of competitive and cooperative interactions in microbial communities. The FRT is replete with host-associated glycans in the form of glycoproteins, epithelial glycogen stores, and the breakdown products of these glycans. I hypothesized that host-associated glycans drive environment, microbe–microbe and host–microbe interactions in the FRT. Methods We have developed robust, scalable, high-throughput culturing systems to empirically define the substrate utilization traits from more than 60 unique bacterial species capable of colonizing the vagina. In addition, we are using batch and continuous culture in vitro cultivation of multispecies communities to study vaginal bacteria within the complex community, that closely recapitulate key dynamics observed in vivo. Results Demonstrating the power of these in vitro models, I have defined the carbohydrate utilization profiles of hundreds of unique FRT isolates, identifying species and strain-level variation in utilization of host-derived carbohydrates. Given the known abundance of glycogen in the vaginal epithelium, I hypothesized that the utilization of host-associated glycogen represents an adaptation to the vaginal environment. Indeed, we identify glycogen degradation enzymes in diverse species resident in the reproductive tract, and find enrichment in genes encoding glycogen-degrading enzymes in L. crispatus strains derived from vaginal as opposed to intestinal sites. Metatranscriptomic analyses from human samples demonstrate that bacterial glycogen and maltose (a breakdown product of glycogen) utilization genes are highly expressed in the vagina and elucidate patterns of gene expression suggestive of context-dependent competition and cooperation for glycogen utilization in vivo. To empirically investigate the impact of glycogen availability and glycogen utilization in FRT microbiota communities, I assembled type strains or co-resident consortia into model, polymicrobial communities in vitro. These studies demonstrate that among health-associated L. crispatus strains, those that use glycogen have a competitive advantage during growth in a complex community. However, preliminary results suggest that some strains may benefit from cross-fed nutrients liberated by other members of the consortium. Conclusions Taken together, these data establish that strain-level variability in glycan utilization contributes to competitive fitness during growth in community, and suggest that these traits may influence community stability or persistence in vivo. Moreover, the methods we have developed provide a scalable system in which to empirically study ecological dynamics within complex community ex vivo.

Human vaginal microbiota colonization is regulated by female sex hormones in a mouse model

“…Since not all mice were colonized equally with different bacteria, we wanted to test methods to improve colonization. Nutrient availability is an important determinant of what species colonize the VMB ( Hood-Pishchany and Rakoff-Nahoum, 2021 ). Glycogen is a common nutrient source used by Lactobacillus species ( Mirmonsef et al., 2014 ) and mucin is a common nutrient source used by G. vaginalis ( Dupont, 2020 ; Vagios and Mitchell, 2021 ).…”

“…An additional optimization of our model was done by examining the effect of nutrient availability in the mouse vaginal canal, as this is an important determinant of what species colonize the VMB ( Hood-Pishchany and Rakoff-Nahoum, 2021 ). As mentioned previously, glycogen is a common nutrient source used by Lactobacillus species ( Mirmonsef et al., 2014 ) and mucin is a common nutrient source used by G. vaginalis ( Dupont, 2020 ; Vagios and Mitchell, 2021 ).…”

Human vaginal microbiota colonization is regulated by female sex hormones in a mouse model

“…Since not all mice were colonized equally with different bacteria, we wanted to test methods to improve colonization. Nutrient availability is an important determinant of what species colonize the VMB (Hood-Pishchany and Rakoff-Nahoum, 2021). Glycogen is a common nutrient source used by Lactobacillus species (Mirmonsef et al, 2014) and mucin is a common nutrient source used by G .…”