A microfluidics-based in vitro model of the gastrointestinal human-microbe interface

Pranjul Shah, Joëlle V. Fritz, Enrico Glaab, Mahesh S. Desai, Kacy Greenhalgh, Audrey Frachet, Magdalena Niegowska, Matthew Estes, Christian Jäger, Carole Seguin-Devaux, Frederic Zenhausern, Paul Wilmes

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157 Scopus citations

Abstract

Changes in the human gastrointestinal microbiome are associated with several diseases. To infer causality, experiments in representative models are essential, but widely used animal models exhibit limitations. Here we present a modular, microfluidics-based model (HuMiX, human-microbial crosstalk), which allows co-culture of human and microbial cells under conditions representative of the gastrointestinal human-microbe interface. We demonstrate the ability of HuMiX to recapitulate in vivo transcriptional, metabolic and immunological responses in human intestinal epithelial cells following their co-culture with the commensal Lactobacillus rhamnosus GG (LGG) grown under anaerobic conditions. In addition, we show that the co-culture of human epithelial cells with the obligate anaerobe Bacteroides caccae and LGG results in a transcriptional response, which is distinct from that of a co-culture solely comprising LGG. HuMiX facilitates investigations of host-microbe molecular interactions and provides insights into a range of fundamental research questions linking the gastrointestinal microbiome to human health and disease.

Original languageEnglish (US)
Article number11535
JournalNature communications
Volume7
DOIs
StatePublished - May 11 2016

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Shah, P., Fritz, J. V., Glaab, E., Desai, M. S., Greenhalgh, K., Frachet, A., Niegowska, M., Estes, M., Jäger, C., Seguin-Devaux, C., Zenhausern, F., & Wilmes, P. (2016). A microfluidics-based in vitro model of the gastrointestinal human-microbe interface. Nature communications, 7, [11535]. https://doi.org/10.1038/ncomms11535