Description
New Insight into the Ecological Role for Host-associated Glycans in the Reproductive Tract
Marguerite I. Hood Pishchany1, MD, PhD, Seth Rakoff-Nahoum1,2, MD, PhD
1Division of Infectious Diseases, 2Division of Gastroenterology, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115
The vaginal microbiome is emerging as central to reproductive tract health, impacting the risk of infection, preterm birth, and HIV acquisition. Despite this importance, we know relatively little about the ecological drivers that shape the female reproductive tract (FRT) microbiome. 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. We hypothesized that host-associated glycans drive environment, microbe-microbe and host-microbe interactions in the FRT. To test this hypothesis, we developed model systems to dissect the ecology and niche occupation of the human FRT microbiome and have begun to comprehensively define the landscape of nutrient utilization of FRT bacteria. Demonstrating the power of these in vitro models, we have defined the carbohydrate utilization profiles of approximately 60 unique FRT isolates. Strikingly, while utilization of mono- and disaccharides tends to segregate by species, utilization of more complex carbohydrates represents a major source of strain-level variation within a given species. We hypothesized that host-associated glycan utilization represents an adaptation to the vaginal environment, and tested the competitive fitness of our bacterial isolates in model, multispecies communities. In these model, polymicrobial communities, we found that bacterial isolates that encode the ability to degrade specific host polysaccharides, gained a competitive advantage over isolates of the same species that lacked these traits. In summary, we have developed robust, high-throughput methods for studying FRT isolates in both axenic and multispecies cultures. Using these methods, we have determined that glycan utilization traits vary at both the species and strain level among FRT bacteria. Importantly, strain-level variability in glycan utilization contributes to competitive fitness of these isolates in complex community, suggesting that these traits could influence community stability or persistence in vivo.