Function-based selection of synthetic communities enables mechanistic microbiome studies

The ISME Journal, vol. 19

Abstract

Understanding the complex interactions between microbes and their environment requires robust model systems such as synthetic communities (SynComs). We developed a functionally directed approach to generate SynComs by selecting strains that encode key functions identified in metagenomes. This approach enables the rapid construction of SynComs tailored to any ecosystem. To optimize community design, we implemented genome-scale metabolic models, providing in silico evidence for cooperative strain coexistence prior to experimental validation. Using this strategy, we designed multiple host-specific SynComs, including those for the rumen, mouse, and human microbiomes. By weighting functions differentially enriched in diseased versus healthy individuals, we constructed SynComs that capture complex host-microbe interactions. We designed an inflammatory bowel disease SynCom of 10 members that successfully induced colitis in gnotobiotic IL10-/- mice, demonstrating the potential of this method to model disease-associated microbiomes. Our study establishes a framework for designing functionally representative SynComs of any microbial ecosystem, facilitating mechanistic study.

Authors 9

1. Thomas C. A. Hitch corresponding Aachen Functional Microbiome Research Group Institute of Medical Microbiology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Functional Microbiome Research Group, Institute of Medical Microbiology, University Hospital of RWTH Aachen , Pauwelsstrasse 30, Aachen, 52074, North Rhine-Westphalia ,

   Functional Microbiome Research Group, Institute of Medical Microbiology, University Hospital of RWTH Aachen, Aachen, Germany

2. Silvia Bolsega

   Medizinische Hochschule Hannover

   Affiliation as printed

   Institute for Laboratory Animal Science, Hannover Medical School , Carl-Neuberg Str. 1, Hannover, 30625, Lower Saxony ,

   Institute for Laboratory Animal Science, Hannover Medical School, Hannover, Germany

3. Charlotte Deschamps

   Université Clermont Auvergne · Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement · Microbiologie Environnement Digestif Santé

   Affiliation as printed

   UMR 454 MEDIS, Microbiologie Environnement Digestif et Santé, Université Clermont Auvergne, INRAE , UMR 454 MEDIS, 28 place Henri Dunant, F-63000 Clermont-Ferrand ,

   UMR 454 MEDIS, Microbiologie Environnement Digestif et Santé, Université Clermont Auvergne – INRAE , Clermont-Ferrand ,

4. Lucie Etienne‐Mesmin

   Université Clermont Auvergne · Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement · Microbiologie Environnement Digestif Santé

   Affiliation as printed

   UMR 454 MEDIS, Microbiologie Environnement Digestif et Santé, Université Clermont Auvergne, INRAE , UMR 454 MEDIS, 28 place Henri Dunant, F-63000 Clermont-Ferrand ,

   UMR 454 MEDIS, Microbiologie Environnement Digestif et Santé, Université Clermont Auvergne – INRAE , Clermont-Ferrand ,

5. Nicole Simone Treichel Aachen Functional Microbiome Research Group Institute of Medical Microbiology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Functional Microbiome Research Group, Institute of Medical Microbiology, University Hospital of RWTH Aachen , Pauwelsstrasse 30, Aachen, 52074, North Rhine-Westphalia ,

   Functional Microbiome Research Group, Institute of Medical Microbiology, University Hospital of RWTH Aachen, Aachen, Germany

6. Stéphanie Blanquet‐Diot

   Université Clermont Auvergne · Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement · Microbiologie Environnement Digestif Santé

   Affiliation as printed

   UMR 454 MEDIS, Microbiologie Environnement Digestif et Santé, Université Clermont Auvergne, INRAE , UMR 454 MEDIS, 28 place Henri Dunant, F-63000 Clermont-Ferrand ,

   UMR 454 MEDIS, Microbiologie Environnement Digestif et Santé, Université Clermont Auvergne – INRAE , Clermont-Ferrand ,

7. Soeren Ocvirk

   German Institute of Human Nutrition · Technical University of Munich

   Affiliation as printed

   Gnotobiology Research Unit, German Institute of Human Nutrition Potsdam-Rehbruecke , Arthur-Scheunert-Allee 114-116, Nuthetal, 14558, Brandenburg ,

   Research Group WESTGUT, ZIEL-Institute for Food & Health, Technical University of Munich , Gregor-Mendel-Str. 2, Freising, 85354, Bavaria ,

   Intestinal Microbiology Research Group, German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal, Germany

   ZIEL – Institute for Food and Health, Technical University of Munich , Freising ,

8. Marijana Basic

   Medizinische Hochschule Hannover

   Affiliation as printed

   Institute for Laboratory Animal Science, Hannover Medical School , Carl-Neuberg Str. 1, Hannover, 30625, Lower Saxony ,

   Institute for Laboratory Animal Science, Hannover Medical School, Hannover, Germany

9. Thomas Clavel corresponding Aachen Functional Microbiome Research Group Institute of Medical Microbiology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Functional Microbiome Research Group, Institute of Medical Microbiology, University Hospital of RWTH Aachen , Pauwelsstrasse 30, Aachen, 52074, North Rhine-Westphalia ,

   Functional Microbiome Research Group, Institute of Medical Microbiology, University Hospital of RWTH Aachen, Aachen, Germany