High-precision functional profiling of microbial communities and the human microbiome

Among many surprising insights, the genomic revolution has helped us to realize that we´re never alone and, in fact, barely human. For most of our lives, we share our bodies with some ten times as many microbes as human cells. They are resident in our gut and on nearly every body surface, and they are a normal part of human health. Within the past decade, new “computational microscopes” have changed our understanding of the microbiome´s importance in maintaining health and mitigating disease. I will discuss recent work in computational methods to functionally profile the human microbiome and other microbial communities, using integration of longitudinal metagenomic, metatranscriptomic, metabolomic, and proteomic approaches. Methodologically, these have driven the development of efficient, robust algorithms for high-throughput sequence analysis in the presence of hundreds or thousands of distinct microorganisms. Applications in areas such as epidemiology-scale inflammatory bowel disease and type 1 diabetes have led to improved understandings of the gut´s redox- and inflammation-driven functional dysbiosis during Crohn´s disease and ulcerative colitis, as well as parallel changes that occur early in the development of type 1 diabetes. I will conclude with comments on open methodological and analytical challenges in translating multi´omic data from the microbiome into detailed mechanistic hypotheses.