Computer-guided design of optimal microbial consortia for immune system modulation.

Elife
Authors
Keywords
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 (T) data from germ-free mice, we estimate the contributions of twelve Clostridia strains with known immune-modulating effect to T induction. Combining this with a longitudinal data-constrained ecological model, we predict the ability of every attainable and ecologically stable subconsortium in promoting T activation and rank them by the T Induction Score (TrIS). Experimental validation of selected consortia indicates a strong and statistically significant correlation between predicted TrIS and measured T. We argue that computational indexes, such as the TrIS, are valuable tools for the systematic selection of immune-modulating bacteriotherapeutics.

Year of Publication
2018
Journal
Elife
Volume
7
Date Published
2018 04 17
ISSN
2050-084X
DOI
10.7554/eLife.30916
PubMed ID
29664397
PubMed Central ID
PMC5959721
Links
Grant list
R15 AI112985 / AI / NIAID NIH HHS / United States
P41 GM103504 / GM / NIGMS NIH HHS / United States
P41 GM103504 / NH / NIH HHS / United States
P30 DK034854 / DK / NIDDK NIH HHS / United States
5R01 GM106303 / GM / NIGMS NIH HHS / United States
R15-AI112985-01A1 / AI / NIAID NIH HHS / United States