Pushing back the boundaries: Connecting spatial organization to function and interaction within the gut

Interest in the physical properties of microbial communities is as old as microbiology itself. In the 1600s, Antonie van Leeuwenhoek exploited his newfound powers of microscopy to discover that microorganisms living on and in his body showed a huge range in shape and size.  This first rudimentary evidence that the human body harbors a microbiota also established the first hint of complex microbial ecosystems.  Now, almost 400 years later, a renaissance of the study of microbiota spatial organization, driven by coincident revolutions in imaging and sequencing technologies, is revealing functional relationships between gut biogeography and health. In this review, we present our current understanding of principles governing the localization of intestinal bacteria, and spatial relationships between bacteria and their hosts. We further discuss important emerging directions that will enable moving from the inherently descriptive nature of localization and –omics technologies to provide functional, quantitative, and mechanistic insight into this complex ecosystem.