Perturbation of the Human Microbiome: Unrest at Home

Complex microbial ecosystems occupy the cutaneous and mucosal surfaces of humans. Recent advances in our understanding of these ecosystems have highlighted the tremendous diversity of these communities, features of individuality, conserved and personalized predicted functional attributes, and their importance to host physiology. Questions remain about the ecological processes that establish and maintain the human microbiota throughout life, as well as the features of community robustness that are associated with stability, and with prevention of invasion or successful competition by potential pathogens. We have examined the distal gut microbiota of healthy human subjects over a 10 month period that included two 5-day courses of the antibiotic, ciprofloxacin, separated by 6 months. The effect of the antibiotic on the gut microbiota was profound and rapid, with a loss of diversity and a shift in community composition occurring within 3-4 days of drug initiation.  Recovery was often incomplete, and varied among subjects and between the two courses within subjects. As with other ecosystems, the human distal gut microbiome at baseline is a dynamic regime with a stable average state. Antibiotic perturbation may cause a shift to an alternative stable state, the full consequences of which remain unknown.  Compounded perturbations may lead to unexpected outcomes. From a general perspective, approaches that combine ecological theory and statistics, sequence-based and other molecular assessments of community structure and host response, and standardized clinical measurements may improve our understanding of health and disease within the human supra-organism.