Computer-guided design of optimal microbial consortia for immune system modulation.
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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
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Journal | Elife
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Volume | 7
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Date Published | 2018 04 17
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ISSN | 2050-084X
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DOI | 10.7554/eLife.30916
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PubMed ID | 29664397
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PubMed Central ID | PMC5959721
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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
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