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The Gut Microbiome

Exploring Complex Microbial Communities

We research microbe-human interactions in the broadest sense, from microbes that act as pathogens in the context of disease and microbes that act as commensals in the context of health—and the wide range of contexts between these extremes. We specialize in developing technologies that enable quantitative understanding of the whole system including the complex interactions among microbes and between microbes and their human host. We also integrate concepts from engineering, dynamical systems, and biophysics to our work.

We are working to understand the interactions among the human gut microbiota, human host, and diet. Our arsenal of tools includes advanced sequencing technologies, high-resolution 3D imaging of gut microbial communities, quantitative analysis of microbial communities, computational modeling, microfluidics, and concepts from engineering and control theory.

For example, food is inextricably linked to our well-being, health, and diseases. Food is also linked to incompletely understood conditions such as malnutrition, metabolic syndrome, and many gastrointestinal disorders. We are working to fill the gaps in our understanding of how food impacts us.  For example, food is rich in polymers but the biophysical mechanisms by which these polymers affect us are not well-understood.  Our gut microbes mediate our interactions with food, yet little is known about the microbiota of the human small intestine, where more of our food is digested and absorbed—by far, most microbiome research has been done using fecal samples and animal models.

Our approach to microbiome research is rigorous and quantitative:

WHERE we measure: We take care to sample the "right" places for making biological insights. Most microbiome research looks at fecal samples because they are easy to acquire and straight-forward to analyze. We focus on the small intestine and other areas of the gastrointestinal tract, specifically looking at the mucosal surface where microbes are in closest proximity to their human host. We also prioritize work with human clinical samples.

HOW we measure: We perform quantitative analyses so that we can acquire absolute abundances of individual microbial taxa, whereas most of the microbiome field has analyzed only relative abundances. Further, we perform high-sensitivity analyses because we recognize that even microbes at low absolute abundances (missed by most technologies) can be biologically important.

WHAT we measure: We go beyond taxonomical analyses (e.g., 16S rRNA sequencing to identify bacteria) and analyze full genomes. We go beyond DNA analyses and include RNA. We go beyond chromosomes and include extrachromosomal elements. We also measure the biophysical aspects of these systems and how they are impacted by the host and by the microbes (e.g., the role of mucus, polymers such as fibers in the diet, etc.)

We recently performed the largest study to date on the human duodenal microbiome (See Publications page, ref #164), and we have received NIH funding to study the human microbiome in the context of celiac disease (See Publications page, ref #168 and the NIH RePORTER abstract for the project).