Human, microbial, and molecular populations in the microbiome

Curtis Huttenhower

Professor of Computational Biology and Bioinformatics, - Harvard University, T.H. Chan School of Public Health, Boston, Massachusetts

2.30 p.m. - Aula B105
Via Sommarive, 9 - Povo, Trento

Studies of the human microbiome have shown that successful applications of microbiome science to human health require a surprising degree of personalization, ecological, and molecular detail. This implies both quantitative methods and population-scale study designs that can pinpoint microbial mechanisms of bioactivity, despite the microbiome's tremendous degree of inter-individual and inter-population variability. Projects such as the second phase of the Human Microbiome Project (HMP2) have particularly highlighted this need, by identifying dynamica, longitudinal mechanisms of host-microbiome interaction in disease. In addition to providing a community resource of human and microbial multi'omics data, protocols, and computational methods, our study (the Inflammatory Bowel Disease Multi'omics Database, IBDMDB) followed a total of 132 Crohn's disease, ulcerative colitis patients, and control subjects for one year each to analyze 2,965 stool, biopsy, and blood specimens. These provide a comprehensive view of the gut microbiome’s functional dysbiosis during IBD activity, showing a characteristic balance between facultative and obligate anaerobes, as well as molecular disruptions in microbial transcription (e.g. among the clostridia), metabolite pools (e.g. acylcarnitines, bile acids, and short-chain fatty acids), and host serum antibody levels, among others. Disease was also marked by greater temporal variability, with characteristic taxonomic, functional, and biochemical shifts. Future studies must build on these techniques and results to integrate diverse molecular profiles of the microbiome in large populations, including the Human Microbiome Bioactives Resources and the BIOM-Mass initiative to survey 25,000 prospectively-followed individuals by the Harvard Chan Center for the Microbiome in Public Health. Finally, I will discuss the challenges remaining in effectively designing population studies to focus on specific targets for translation and improvements in health.