The diverse bacterial populations that comprise the commensal microbiome of the human intestine play a central role in health and disease. A method that sustains complex microbial communities in direct contact with living human intestinal cells and their overlying mucus layer in vitro would thus enable the investigation of host–microbiome interactions. Here, we show the extended coculture of living human intestinal epithelium with stable communities of aerobic and anaerobic human gut microbiota, using a microfluidic intestine-on-a-chip that permits the control and real-time assessment of physiologically relevant oxygen gradients. When compared to aerobic coculture conditions, the establishment of a transluminal hypoxia gradient in the chip increased intestinal barrier function and sustained a physiologically relevant level of microbial diversity, consisting of over 200 unique operational taxonomic units from 11 different genera and an abundance of obligate anaerobic bacteria, with ratios of Firmicutes and Bacteroidetes similar to those observed in human faeces. The intestine-on-a-chip may serve as a discovery tool for the development of microbiome-related therapeutics, probiotics and nutraceuticals.
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The main data supporting the findings of this study are available in the Article and Supplementary Information. The raw data generated in this study are available from the corresponding author on reasonable request.
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This research was supported by a US FDA grant (HHSF223201310079C), a DARPA THoR grant (W911NF-16-C-0050), the Bill & Melinda Gates Foundation, the Wyss Institute for Biologically Inspired Engineering at Harvard University and Fundação para a Ciência e a Tecnologia Portugal (project PD/BD/105774/2014 at the Institute for Bioengineering and Biosciences). We thank D. E. Achatz (PreSens GmbH) for providing oxygen-sensing particles and for her expert technical advice and T. Ferrante for his assistance with imaging.
D.E.I. holds equity in Emulate, Inc., consults for the company and chairs its scientific advisory board.
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Jalili-Firoozinezhad, S., Gazzaniga, F.S., Calamari, E.L. et al. A complex human gut microbiome cultured in an anaerobic intestine-on-a-chip. Nat Biomed Eng 3, 520–531 (2019). https://doi.org/10.1038/s41551-019-0397-0
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