Tracing the origins and evolution of human microbiome investigations: from pursuit of earth’s earliest life forms to the etiology of Pouchitis

Practitioners of biodiversity (a form of political ecology) treated the microbial world as an after-thought with only 5000 named taxa. Nearly one hundred years after discovery of the microbial world, scientists could only identify and classify microbes by morphology, cell-staining characteristics, physiological properties, and by the chemical reactions they perform.  The limited morphological complexity discernable through light microscopy and the requirement to grow microbes in the laboratory for identifying phenotypic features that can serve as taxonomic determinants constrained our ability to differentiate between kinds of microbes.  Despite heroic efforts during the initial 100 years of microbiology, the lack of agreement about which phenotypic features were most valuable for defining microbial systematics led to conflicting views of their natural relationships and gross underestimates of diversity. It took a physicist in search of the origins of life to arrive at a solution. Carl Woese argued that molecular data could provided a practical metric for assessing evolutionary relationships between cultivated micro organisms. From molecular based phylogenetic trees he anticipated identification of the deepest branches in the tree of life and ultimately discovered Archaea – the third major domain of life. Over the last 60 years advances in sequencing and informatic technology revealed a far more complicated evolutionary history for single-cell organisms including those that cause disease. Initially using high-throughput marker gene analyses (rRNA sequencing) and more recently binning of assembled contigs from shotgun metagenomic datasets, human microbiome investigations have begun to unveil the complex microbial etiology of disease by providing insights into the transition of host associated microbes into potential pathobionts such as those associated with Inflamatory Bowel Disease (IBD).