David A. Relman, Stanford School of Medicine and Brendan Bohannan, University of Oregon.
Background/Question/Methods: Complex microbial ecosystems occupy the cutaneous and mucosal surfaces of humans. Recent advances have highlighted both the tremendous diversity of these communities and their importance to host physiology, yet, we have only scratched the surface. Questions remain about the ecological processes that establish and maintain the human microbiota throughout life. Furthermore, basic features of the human microbial ecosystem remain poorly described, including variability in diversity, in space and time and between individuals. We are exploring spatial patterning and the effects of perturbation on human microbial diversity. Our methods include clinical sampling of humans (oral soft tissue, tooth, and subgingival crevice, intestinal biopsies and brushings, and feces), broad range 16S rDNA PCR, both clone library sequencing and pyrosequencing of both PCR products and community DNA, sequence-based profiling of community taxonomic and phylogenetic composition, and ecological statistics.
Results/Conclusions: In the healthy human mouth, we have found evidence for island-like biogeography, where every sampled tooth reveals a non-random subset of overall bacterial diversity in that mouth at that point in time. Mouths from different healthy individuals display distinct overall profiles of diversity. In a study of healthy humans before and after 5 days of treatment with the fluoroquinolone antibiotic, ciprofloxacin, and an analysis of their feces, we have found that ciprofloxacin treatment influenced the abundance of about a third of the bacterial taxa in the distal gut, decreasing the taxonomic richness, diversity and evenness of the community. Yet, the taxonomic composition of the community closely resembled its pre-treatment state by 4 weeks after the end of treatment. We are currently examining the temporal dynamics of this perturbation in more detail and in additional subjects. The rapid return to the pretreatment community composition is indicative of factors promoting community resilience. Approaches that combine ecological theory and statistics, sequence-based and other molecular assessments of community structure, and standardized clinical measurements may improve our understanding of health and disease within the communal human organism. By understanding the patterns of diversity associated with human health, we may be able to preserve and restore health more effectively. Perturbation may reveal aspects of community stability and resilience that can be exploited for maintaining and restoring health. By recognizing the early signs of impending disturbance, we may be able to predict and avoid disease.