Listeria monocytogenes (Lm) is a bacterial pathogen associated with serious pregnancy complications, including miscarriage, stillbirth, preterm birth, neonatal sepsis, and meningitis. A ubiquitous bacterium, Lm is primarily contracted via consumption of contaminated food. Once ingested, Lm encounters the gastrointestinal tract and its microflora where it then replicates to establish infection. However, very little is known about how the microbial presence within the intestines influences infection outcome. Epidemiological studies have found associations between overall health and gut microbial diversity, indicating that bacterial dysbiosis may influence susceptibility to disease and inflammation within the intestinal lumen. Furthermore, the gut microbiome may play a crucial role during pregnancy, by providing resistance to opportunistic pathogens which could lead to adverse pregnancy outcomes (APOs). The unique susceptibility to Lm during the pregnant state, as well as the severe consequences of infection during pregnancy, implore a deeper understanding of the influence of microbial composition on Lm pathogenicity within the gut. We hypothesize that the unique state of pregnancy is associated with increased bacterial burden of listeria within the intestines, feces, and blood as well as dysbiosis to the gut microbial communities. Furthermore, we hypothesize that during the nonpregnant state, there are microbial communities within the gut that are robust and resistant to displacement, which may be susceptible to displacement during pregnancy. Using nextgen sequencing we aim to further understand the possible implications of the maternal microbiomes and their potential impact on APOs. 

We have established an in vivo monkey model to directly investigate the mechanisms that cause early pregnancy loss with bacterial infection, using Listeria monocytogenes as a model organism. Listeria is typically contracted from eating contaminated food products. The intracellular bacteria can disseminate from the gastrointestinal tract to the reproductive tract in pregnant women, and pose a significant risk to fetal health. We have found a high risk for fetal infection and demise in early pregnancy, and our results have suggested a previously underappreciated role of decidual infection in initiating bacterial transmission to the fetus through placental infection. During the pregnancy studies, we noted rapid bacteremia and fecal shedding of Listeria, but in subsequent studies with nonpregnant animals, were surprised to be unable to detect the organism either in the feces or in the blood. 

While there are different interpretations of these observations, one intriguing possibility is that feeding with Listeria in pregnant and nonpregnant animals has different impact on the gut microbiota. There is a great deal of interest in the physiological axes influenced by organisms in the gut, and we are conducting sequencing of the ribosomal RNA genes in feces from infected and control, pregnant and nonpregnant macaques to allow us to understand the impact of pregnancy and listeriosis on the gut microbiome, and whether changes in the gut are associated with adverse pregnancy outcomes linked to Listeria feeding.