Synthetic ecology of the human gut microbiota

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Despite recent advances in sequencing and culturing, a deep knowledge of the wiring and functioning of the human gut ecosystem and its microbiota as a community is still missing. A holistic mechanistic understanding will require study of the gut microbiota as an interactive and spatially organized biological system, which is difficult to do in complex natural communities. Synthetic gut microbial ecosystems can function as model systems to further current understanding of the composition, stability and functional activities of the microbiota. In this Review, we provide an overview of the current synthetic ecology strategies that can be used towards a more comprehensive understanding of the human gut ecosystem. Such approaches that integrate in vitro experiments using cultured isolates with mathematical modelling will enable the ultimate goal: translating mechanistic and ecological knowledge into novel and effective therapies.

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Fig. 1: Timeline of select highlights in the sequencing and culturing of the human gut microbiota.
Fig. 2: Gaps between sequenced, cultured and experimentally verified interacting bacterial species in the human gut microbiota.
Fig. 3: In vitro culture systems for batch and continuous culture of gut microbiota.
Fig. 4: Connections between different types of human gut microbiota models.


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The authors thank all members of the Raes laboratory, as well as D. Gonze, for the many discussions that contributed to this work. G.H. is supported by the European Union’s Horizon 2020 Research and Innovation Programme (EU H2020) AD-GUT project, grant agreement no. 686271. The Raes laboratory is supported by the VIB Grand Challenges Programme, the Rega Institute for Medical Research, KU Leuven, the FWO EOS Programme (30770923), FP7 METACARDIS (305312) and the H2020 initiatives SYSCID (733100), PIBD-SET (668023) and IMMUNAID (779295); K.F. has received funding from the European Research Council (ERC) under EU H2020 grant agreement no. 801747.

Author information

G.V. provided scoping and coordination. G.V. and A.C.G. wrote the introduction and the sections on in vitro systems and future strategies; A.C.G. made draft figures; G.R.B.H. contributed the section on isolation; and K.F., the section on mathematical modelling as well as the table. J.R. provided overall guidance. All authors polished and approved the text.

Correspondence to Jeroen Raes.

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Nature Reviews Microbiology thanks Samuel Forster and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Related links

Human Microbiome Project:

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Qualitative and quantitative changes in the intestinal microbiota that alter their metabolic activities and local distributions.


The process by which one organism uses the metabolic products of another organism.


A type of cooperative bidirectional cross-feeding whereby two organisms gain through the metabolic reactions of each other.


A type of cross-feeding whereby the metabolic reactions of one organism are required for the growth of another organism.


The ability of a system to withstand disturbance.


The ability of a system to recover from disturbance.

Metagenome-assembled genomes

(MAGs). Genomes assembled using sequencing data from environmental samples.

Tipping points

Thresholds at which, if conditions are changed beyond that level, the system suddenly switches to a different state.

Operational taxonomic units

(OTUs). Operational definitions used to classify and group closely related organisms.


Groups of phylogenetically related organisms.

Xenobiotic transformations

Biological transformation of the chemical structure of a molecule normally absent from the microbial ecosystem, such as pharmaceuticals, pesticides and so forth.


Nutrients that, besides macronutrient components, also have pharmaceutical properties.


Without microbial commensals.


Tissue-culture-generated structures from certain human cell types, in this paper to be understood as differentiated gut tissue.

Core microbiome

The collection of gut organisms common to the majority of subjects in a given population.


Serial dilution of a microbial sample to extremely low densities that allow the isolation of single cells.

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