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  • Review Article
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Modelling host–microbiome interactions in organ-on-a-chip platforms

Nature Reviews Bioengineering volume 2, pages 175–191 (2024)Cite this article

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Abstract

The human microbiome orchestrates a variety of metabolic, immunological and regulatory functions in health and disease. However, experimentally dissecting host–microbiome interactions remains challenging. In this Review, we discuss how human organ-on-a-chip platforms can be designed to study fundamental microbiome mechanisms, investigate microbiome-related disease pathophysiology and provide preclinical drug screening platforms, as an alternative to conventional cell cultures or animal models. We outline key design parameters, including spatial configurations, microfluidic setups, mechanical deformation and oxygen gradients, that allow the longitudinal co-culture of aerobic and anaerobic microorganisms with human cells. Such organ-on-a-chip platforms have been explored for the preclinical modelling of microbiome-associated diseases, including infectious and reproductive organ diseases. Moreover, organ-on-a-chip platforms can be engineered to test microbiome-assisted therapeutics, for pharmacomicrobiomics and culturomics investigations, and to model microbiome-mediated multi-organ interactions. Finally, we provide a translational outlook, discussing clinical challenges, regulatory hurdles and precision interventions.

Key points

  • Human organ-on-a-chip platforms allow the investigation of host–microbiome interactions in vitro under controlled physiological and biomechanical dynamics.

  • Organ-on-a-chip models can be designed to recapitulate inter-kingdom crosstalk for preclinical disease modelling and validation of therapeutic interventions.

  • Patient-derived samples, including microbiome and cell samples, can be integrated in organ-on-a-chip platforms to model patient-specific disease milieus, reflecting the genetic and phenotypic parameters of a specific patient.

  • Human organ-on-a-chip platforms can be applied to study human-relevant drug metabolism, bioavailability and toxicity, and to investigate microbiome-associated diseases.

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Fig. 1: Modelling human host–microbiome interactions.
Fig. 2: Gut-on-a-chip platform.
Fig. 3: Translational framework for patient-on-a-chip models.

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Acknowledgements

We thank H. Koh (Yonsei University Severance Hospital), D.-W. Lee (Yonsei University), H. Y. Cho (Seoul National University Hospital) and J.-M. Song (Sungshin Women’s University) for their valuable comments. This work was supported by the Bio-industrial Technology Development Program (20018770) from the Ministry of Trade, Industry & Energy (MOTIE, Korea) and the Senior Research Award from Crohn’s and Colitis Foundation of America (CCFA).

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  1. These authors contributed equally: Yong Cheol Shin, Nam Than.

Authors and Affiliations

  1. Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA

    Yong Cheol Shin, Nam Than, Soyoun Min & Hyun Jung Kim

  2. Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea

    Woojung Shin

  3. Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA

    Hyun Jung Kim

  4. Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH, USA

    Hyun Jung Kim

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European Organ-on-chip Society (EUROoCS): https://euroocs.eu/

Human Microbiome Project Initiative (HMP): https://commonfund.nih.gov/hmp/initiatives

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Shin, Y.C., Than, N., Min, S. et al. Modelling host–microbiome interactions in organ-on-a-chip platforms. Nat Rev Bioeng 2, 175–191 (2024). https://doi.org/10.1038/s44222-023-00130-9

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