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Exploring the Prenatal Microbiome in Mus

Abstract

The developmental environment, including the microbiome, can strongly influence offspring phenotypes. Investigating how microbes interact with developing offspring is the first step in understanding how the prenatal microbiome impacts physiological, immunological, and behavioral phenotypes in adults. In eutherian mammals, the current general consensus is that the placenta does not have a stable microbial community, and that the first microbial inoculation of embryos occurs during birth as offspring move through the vaginal tract. The main critique of early studies of the prenatal microbiome was centered around the high likelihood of contamination in the low-biomass samples. My dissertation addresses if and how species identity and embryonic genotype affect the prenatal microbes in two different mouse systems: first, with a hybrid cross between the house mouse (Mus musculus domesticus) and its sympatric congener, the Algerian mouse (Mus spretus), and second within M. m. domesticus, using two wild-derived strains that have maintained population-specific microbiomes after multiple generations of lab-rearing. Finally, in my last chapter, I utilized multiple methods to determine if live microbes are present in the gut of developing embryos. I found that there was no difference between embryonic guts or placental microbial communities based on embryonic genotype after contaminant removal. However, I observed an effect of embryonic genotype on beta diversity in embryonic guts and placenta in chapter two. Surprisingly, I also found an effect of embryonic genotype on the microbial community composition of maternal guts. Additionally, chapter two investigated which maternal source was the most likely contributor to the embryonic gut microbial community, including the oral cavity, blood, gut, and vaginal tract. Similar to previous reports, my data support the idea that microbes pass through the maternal gut to the circulatory system and, ultimately, from maternal blood flow via the placenta to the embryonic gut. In chapter three, I did not find any evidence of live microbes when attempting to quantify short chain fatty acids (SCFAs), the main products of anaerobic microbes in the adult gut. Despite a lack of evidence of SCFAs in the embryonic gut, prenatal exposure to microbial DNA may still affect embryonic development.

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