Computer-guided design of optimal microbial consortia for immune system modulation
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 compositicon and immune effectors measurements. Using published and newly generated microbial and regulatory T-cell (Treg) data from germ-free mice, we estimate the contributions 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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 17, 2018
- Source ID
- 10.7554/elife.30916
Entities
People
- Bernat Olle
- Chris Sander
- Georg K Gerber
- Jason M Norman
- Kenshiro Oshima
- Kenya Honda
- Masahira Hattori
- Richard R Stein
- Rose L Szabady
- Shakti K. Bhattarai
- Takeshi Tanoue
- Vanni Bucci
- Wataru Suda
Organizations
- Brigham and Women's Hospital
- Broad Institute
- Core Research for Evolutional Science and Technology
- Defense Advanced Research Projects Agency
- Harvard Medical School
- Harvard University
- Human Frontier Science Program
- Japan Agency for Medical Research and Development
- Keio University
- National Institute of Allergy and Infectious Diseases
- National Institute of General Medical Sciences
- National Institutes of Health
- National Science Foundation
- RIKEN Center for Integrative Medical Sciences
- Takeda Science Foundation
- University of Massachusetts Dartmouth
- University of Tokyo