ASM General Meeting 2015

Tom and Chris both delivered excellent presentations at American Society for Microbiology general meeting in New Orleans. Chris presented a poster entitled "Zebrafish as a Model for the Interactions Between Hosts, Microbiomes, and the Environment" and Tom presented his work on shotMAP in an oral presentation titled "Accurate and High-throughput Metagenome Annotation Reveals Differences in Enteric Microbiome Function that Associate with Inflammatory Bowel Disease". Both presentations were well received and generated lots of interesting discussion. The abstracts for both presentations follow below.

Zebrafish as a Model for the Interactions Between Hosts, Microbiomes and the Environment

Growing evidence suggests that the microbiome plays an important role in gastrointestinal homeostasis. Alterations in community structure are often associated with changes in host physiology, indicating that ecological disturbance of the microbiome may have profound impacts on health. A major objective in microbiome research involves understanding the environmental factors that influence community disturbance. The zebrafish provides a unique system in which we can investigate these factors as it is in constant contact with its environment. Although zebrafish have been a crucial animal model used to explore the interactions between gut microbes and their hosts, there are substantial unknowns regarding the zebrafish microbiome that warrant clarification. For example, little is known about the functional capacity of these microbial communities, how they vary across animals and facilities, and how this variation corresponds to the composition of the microbiome. Here we investigated the composition and variability of the zebrafish gut microbiome by subjecting intestinal contents of zebrafish housed at two facilities to shotgun metagenomic and 16S rRNA sequencing. Similar to findings at other institutions, our zebrafish microbial communities consisted primarily of two phyla, Proteobacteria and Fusobacteria, the abundance of which varied across the two facilities. We additionally quantified the structural variation between zebrafish microbiomes collected from different tanks and over time, and characterized the functional profiles and variance of these communities. Finally, we measured the impact of antibiotic exposure as a model environmental perturbation on microbiome structure. These experiments provide important insight into the physiological potential of the zebrafish microbiome and establish a framework for future experimental evaluations of the impact of perturbations on the structure and function of zebrafish microbial communities.

Accurate and High-throughput Metagenome Annotation Reveals Differences in Enteric Microbiome Function that Associate with Inflammatory Bowel Disease

Shotgun metagenome annotation is a widely used method that provides insight into the genomic content and functional potential of microbial communities. While several annotation tools exist, little is known about how the analytical decisions made during annotation (i.e., homology classification thresholds) affect the reliability of the results. We used statistical simulations to quantify how properties of the input data (e.g., read length, library size) and user-defined analytical decisions impact annotation accuracy and speed. This analysis identified best practices in metagenome annotation, which we used to guide the development of analytically flexible, end-to-end annotation software known as the Shotgun Metagenome Annotation Pipeline (ShotMAP). We used ShotMAP to functionally profile metagenomes obtained from a clinical microbiome investigation of inflammatory bowel disease. Our analysis found that stool microbiomes collected from Crohn’s disease patients are functionally distinct from those collected from either ulcerative colitis patients or healthy controls. This work also identified specific metabolic pathways, such as Lipid A biosynthesis, GAG degradation, and short chain fatty acid biosynthesis, that stratify Crohn’s disease patient microbiomes. We subsequently quantified how enteric microbiome function diversifies over the course of disease development using a mouse model of Crohn’s disease and identified microbiome functions that correlate with disease severity. These results, which were discovered due to the statistically guided framework underlying ShotMAP, provide insight into how hosts and their microbiomes interact in the context of Crohn’s disease and may serve as putative clinical biomarkers.