Doctoral Dissertation Research: Microbial Community Assembly in Primates

Duke University, Durham NC

Investigators

Abstract

The gut is home to tens of trillions of bacteria that are integral for nutrient digestion, gut development, and defense against disease. But it is not clear how these communities of microbes are established, how they respond to diet and disease, and how they may change through an individual's life. This project will characterize and compare the colonization process from birth to weaning in infants of three lemur species, each with a unique gut morphology and life history. Additional sampling from the weaned infants of one lemur species will track the re-colonization process after infection with Cryptosporidium, an intestinal pathogen. Colonization after birth and disease will be compared to elucidate the rules governing gut community development. Because lemurs and humans are both primates, the study findings may have a profound impact on current understanding of the role of microbiota in human health and development. Additional broader impacts include training of a female graduate student in the STEM sciences, and extensive public science education and outreach efforts. This two-year project will analyze bacterial 16S rDNA and metagenomic profiles to tease apart the potentially divergent effects of host phylogenetic history and diet on the gut microbiota community structure and to examine the associated microbial signatures for potential effects on lemur health and nutritional uptake. Fecal samples will be collected at the Duke Lemur Center from Varecia variegata (frugivorous), Lemur catta (generalist), and Propithecus coquereli (folivorous). DNA will be extracted and sequenced using two different approaches to determine which bacterial species are present and what functions each community can perform. First, the v4 region of the 16S gene will be sequenced and analyzed to identify bacterial taxa and measure their frequencies in each community. Next, the investigators will sequence genomic reads from the entire microbiome, which includes viruses, fungi, protozoans, and other organisms in addition to bacteria. Metagenomic reads will be compared to NCBI databases to identify all (bacterial and non-bacterial) community members, as well as the functions encoded by the genes from each community. This will be the first project to intensively and longitudinally study the composition and community development of gut microbiota across multiple species within a phylogenetically related but ecologically diverse group of mammals, thus enabling modeling of ecological processes in the gut for application to other primates, including humans. A novel bioinformatics pipeline for metagenomic data analysis will be made publicly available as an open source tool through an online repository. The proposed activities will not only shed light on microbial contributions to primate evolution and ecology, but the results will provide a springboard for public education through local outreach.