Biogeography of a human oral microbiome at the micron scale

Significance The physiology and ecology of complex microbial communities are strongly dependent on the immediate surroundings of each microbe, including the identity of neighboring microbes; however, information on the micron-scale organization of microbiomes is largely lacking. Using sequencing data combined with spectral fluorescence imaging, we have discovered a multigenus, highly organized microbial consortium in human dental plaque. The spatial structure of the consortium reveals unanticipated interactions and provides a framework for understanding the organization, metabolism, and systems biology of the microbiome and ultimately, its effect on the health of the human host. Our synthesis of high-throughput sequencing data with spatial and structural information shows the informative value of microbial biogeography at the micron scale. The spatial organization of complex natural microbiomes is critical to understanding the interactions of the individual taxa that comprise a community. Although the revolution in DNA sequencing has provided an abundance of genomic-level information, the biogeography of microbiomes is almost entirely uncharted at the micron scale. Using spectral imaging fluorescence in situ hybridization as guided by metagenomic sequence analysis, we have discovered a distinctive, multigenus consortium in the microbiome of supragingival dental plaque. The consortium consists of a radially arranged, nine-taxon structure organized around cells of filamentous corynebacteria. The consortium ranges in size from a few tens to a few hundreds of microns in radius and is spatially differentiated. Within the structure, individual taxa are localized at the micron scale in ways suggestive of their functional niche in the consortium. For example, anaerobic taxa tend to be in the interior, whereas facultative or obligate aerobes tend to be at the periphery of the consortium. Consumers and producers of certain metabolites, such as lactate, tend to be near each other. Based on our observations and the literature, we propose a model for plaque microbiome development and maintenance consistent with known metabolic, adherence, and environmental considerations. The consortium illustrates how complex structural organization can emerge from the micron-scale interactions of its constituent organisms. The understanding that plaque community organization is an emergent phenomenon offers a perspective that is general in nature and applicable to other microbiomes.