Computer-guided design of optimal microbial consortia for immune system modulation
- Dana-Farber Cancer Institute, United States
- RIKEN Institute, Japan
- Vedanta Biosciences, Inc, United States
- University of Massachusetts, United States
- Keio University School of Medicine, Japan
- The University of Tokyo, Japan
- Brigham and Women's Hospital, United States
Abstract
Manipulation of the gut microbiota holds great promise for the treatment of diseases. However, a major challenge is the identification of therapeutically potent microbial consortia that colonize the host effectively while maximizing immunologic outcome. Here, we propose a novel workflow to select optimal immune-inducing consortia from microbiome composition and immune effectors measurements. Using published and newly generated microbial and regulatory T-cell (Treg) data from germ-free mice, we estimate the contribution of twelve Clostridia strains with known immune-modulating effect to Treg induction. Combining this with a longitudinal data-constrained ecological model, we predict the ability of every attainable and ecologically stable subconsortium in promoting Treg activation and rank them by the Treg Induction Score (TrIS). Experimental validation of selected consortia indicates a strong and statistically significant correlation between predicted TrIS and measured Treg. We argue that computational indexes, such as the TrIS, are valuable tools for the systematic selection of immune-modulating bacteriotherapeutics.
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Funding
National Institutes of Health (P41 GM103504)
- Richard R Stein
- Chris Sander
Brigham and Women's Hospital (Precision Medicine Initiative)
- Georg K Gerber
Defense Advanced Research Projects Agency (BRICS award HR0011-15-C-0094)
- Georg K Gerber
Human Frontier Science Program (RGP00055/2015)
- Chris Sander
Takeda Science Foundation
- Kenya Honda
National Institute of General Medical Sciences (5R01 GM106303)
- Chris Sander
Japan Agency for Medical Research and Development
- Kenya Honda
National Institute of Allergy and Infectious Diseases
- Vanni Bucci
National Science Foundation
- Vanni Bucci
Core Research for Evolutional Science and Technology
- Kenya Honda
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: 11-strain time-series mouse experiments were performed under ethical approval by RIKEN, Keio and Azabu Universities under protocol H24-9(14) (RIKEN). 4-strain validation mouse work was performed at Brigham and Women's Hospital in Boston, MA in the Massachusetts Host Microbiome Center under IACUC protocol 2016N000141.
Copyright
© 2018, Stein et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Computer-guided design of optimal microbial consortia for immune system modulation
eLife 7:e30916.
https://doi.org/10.7554/eLife.30916
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