A Systems Approach to the Human Microbiome
“The trillions of microorganisms that reside in and on our bodies — our microbiome — represent a heretofore unrecognized organ, integral to our health and wellbeing. When the ecology of this organ is compromised, we become vulnerable to a range of complex diseases.”
-Dr. Sean Gibbons, ISB assistant professor
We see an accelerating loss of gut bacterial diversity in industrialized and developing countries. This loss of microbial diversity is driven, in part, by a lack of exposure to maternal and environmental microbes during our development and to shifts in diet and widespread use of antimicrobial compounds. This loss of biodiversity is alarming due to the importance of the microbiome in protecting us from disease, processing our food, and training our immune system.
The loss of gut microbial diversity is associated with the rise of modern plagues, like asthma, allergies, autoimmunity, diabetes, obesity, and other disorders arising from a dysregulated immune system. Loss of diversity is also associated with an increase risk of intestinal-related infections by pathogens like Clostridioides difficile.
Over the last decade, emerging DNA sequencing technologies and computational tools have allowed us to peer directly into the complex ecology of the human microbiome. We have just begun to translate our scientific knowledge of the gut microbiome into ecological therapies for complex human diseases. From fecal transplants to individual-specific nutrition and pharmaceutical-grade probiotics, the human microbiome has emerged as a crucial component of personalized medicine.
WHAT ISB IS DOING
ISB researchers, along with our external partners, are developing computational and wet-lab tools for engineering microbial communities. In particular, we are integrating multi-omics data from human blood and from fecal microbiomes to improve our understanding of how fluctuations in the gut microbiome are reflected in host physiology. By mining large multi-omic data sets, we will identify promissing targets for experimental validation using in vitro and in vivo models of disease. We aim to understand the underlying eco-evolutionary rules governing microbial community assembly and resilience in individual people in order to manipulate the gut ecosystem to improve human health.
To date, our researchers are:
- Integrating host metabolomic, proteomic, and genomic data with microbiome data to better define “microbiome health.”
- Developing metabolic modeling platforms for host-associated microbial communities.
- Designing long-term evolution experiments to determine how our microbiota adapt to us as individuals over the course of our lifespans.
- Running perturbation experiments to determine how antimicrobial and pre-biotic exposures alter the structure and resilience of microbial communities.
- Building new bioinformatic and statistical tools for multi-omic data analyses.
MAKING OUR MARK
ENABLING MECHANISTIC STUDIES OF THE HUMAN MICROBIOME
ISB and our partners have assembled the most comprehensive database to date on individual wellness, with genomic, blood proteomic, blood metabolomic, fecal microbiome, dietary, and behavioral data collected on > 4,000 people. ISB researchers are also working with the Broad Institute and MIT to release a massive data resource containing multi-omic (16S amplicon sequences, metagenomics, and fecal metabolomics) time-series data on 90 healthy stool donors, including 10 long, dense time series (i.e. almost daily sampling for a year or more). This data resource is paired with an extensive, open-access isolate library containing > 5,000 strains and > 2,000 bacterial genomes from all the major genera in the gut.
COMPUTATIONAL METHODS DEVELOPMENT AND META-ANALYSIS OF MICROBIOME DATA
ISB is developing bioinformatic tools for dealing with batch effects, which impede cross-study comparisons. In conjunction with tool development, ISB is working with external collaborators to assemble large, curated databases for large-scale meta-analyses. For example, there is a partnership between ISB and the Microboime Stress Project to assemble data on how various stressors impact microbial communities in environmental and host-associated environments. ISB researchers are also working to assemble all available infant gut time series data to carry out the first cross-study meta-analysis of gut successional dynamics in early life.
- Poyet, M., Groussin, M., Gibbons, S.M., Avila-Pacheco, J., Jiang, X., Kearney, S.M., Perrotta, A.R., Berdy, B., Zhao, S., Lieberman, T., Swanson, P.K., Smith, M., Roesemann, S., Alexander, J.E., Rich, S.A., Livny, J., Vlamakis, H., Clish, C., Bullock, K., Deik, A., Scott, J., Pierce, K.A., Xavier, R., and Alm, E.J. 2019. A library of human gut bacterial isolates paired with longitudinal multiomics data enables mechanistic microbiome research. Nature Medicine, https://doi.org/10.1038/s41591-019-0559-3
- Wilmanski, T., Rappaport, N., Earls, J.C., Magis, A.T., Manor, O., Lovejoy, J., Omenn, G.S., Hood, L., Gibbons, S.M., Price, N.D. 2019. Blood metabolome signature predicts gut microbiome alpha-diversity in humans. NatureBiotechnology, https://doi.org/10.1038/s41587-019-0233-9
- Carr, A., Diener, C., Baliga, N.S., and Gibbons, S.M. 2019. Use and abuse of correlation analyses in microbial ecology. ISME Journal. https://doi.org/10.1038/s41396-019-0459-z
- Shijie Zhao, Tami D. Lieberman, Mathilde Poyet, Kathryn M. Kauffman, Sean M. Gibbons, Mathieu Groussin, Ramnik J. Xavier, Eric J. Alm. 2019. “Adaptive evolution within gut microbiomes of healthy people.” Cell Host & Microbe. https://doi.org/10.1016/j.chom.2019.03.007
- Otwell, A.E., García de Lomana, A.L., Gibbons, S.M., Orellana, M.V., Baliga, N.S. 2018. “Systems biology approaches towards predictive microbial ecology.” Environmental Microbiology. https://doi.org/10.1111/1462-2920.14378
- Price, Nathan D., Andrew T. Magis, John C. Earls, Gustavo Glusman, Roie Levy, Christopher Lausted, Daniel T. McDonald, et al. 2017. “A Wellness Study of 108 Individuals Using Personal, Dense, Dynamic Data Clouds.” Nature Biotechnology. https://doi.org/10.1038/nbt.3870
HOW YOU CAN HELP
ISB’s multi-pronged and collaborative approach to the human microbiome is unique. We have made great strides in developing computational tools and experimental models targeted at engineering the gut microbiome.
However, our work is far from done. Your support is crucial to our quest to integrate the human microbiome into 21st Century medicine.
For more information, please contact:
Renee Duprel | 206.732.1287 | firstname.lastname@example.org