Projects

ecology of the gut microbiome: heterogeneity and assembly

image1

  

The mature human gut microbiota is shaped by diet and environment which is assembled over time.  This contributes to interpersonal variation in gut microbiome composition, which in turn affects health or disease status. Our goal in this project is to better understand the causes and consequences of this gut microbiota assembly. We approach this problem by defining the gut microbiota community composition by using metagenomics and then developing libraries of pure culture isolates from individual samples (Pictured above is the taxonomy of 102 species retrieved from Prevotella enterotype gut microbiome samples . This was done by using single medium based culturomics). Simple to complex communities are then assembled in vitro (bioreactors) or in vivo (germfree animals) to determine the rules governing the community assembly and its effect on host health. 

Mechanistic understanding of the Microbiota-mediated colonization resistance against gut pathogens

image2

  

A healthy microbiome generally excludes pathogens from the gut and prevents infections. This property of the healthy microbiome is called colonization resistance. In this project, we are interested in identifying the keystone species in the gut microbiota that are responsible for conferring colonization resistance. We have isolated a large library of isolates from healthy donors, which we are screening to identify the strains that can inhibit Clostridium difficile, Salmonella enterica, and Vancomycin resistant Enterococcus(VRE). We then determine the mechanistic  basis of colonization resistance, some of which include competition for nutrition, bacteriocin production, volatile fatty acid production, and conversion of primary bile into secondary bile salts. The figure above shows the nutrition utilization profile of pathogen inhibiting gut commensals, determined  using Biolog Phenotype Microarrays. 

Genomic basis of gut pathogen outbreaks

image3

  

Outbreaks caused by gut pathogens such as Salmonella enterica is a major health problem in the United States. Our group is interested in understanding the genomic basis of the outbreak causing strains. In this project, our primary focus is to determine how genomic changes in various Salmonella serotypes contribute to increased virulence, survival in the host, and the environment which ultimately causes outbreaks. We are sequencing whole genomes of hundreds of Salmonella strains collected from 27 US states  and several countries outside North America. We then use phylogenomics to define the transmission patterns and the genomic changes in the outbreak causing strains. The figure above shows the global population structure of Salmonella Mbandaka, which was determined using maximum likelihood whole genome phylogeny.