title: A microfluidics-based in vitro model of the gastrointestinal human-microbe interface.
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.
authors.affiliation: Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 6 avenue du Swing, Belvaux L-4367, Luxembourg.
authors.forename: Pranjul
authors.initials: P
authors.lastname: Shah
authors.affiliation: Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 6 avenue du Swing, Belvaux L-4367, Luxembourg.
authors.forename: Joëlle V
authors.initials: JV
authors.lastname: Fritz
authors.affiliation: Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 6 avenue du Swing, Belvaux L-4367, Luxembourg.
authors.forename: Enrico
authors.initials: E
authors.lastname: Glaab
authors.affiliation: Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 6 avenue du Swing, Belvaux L-4367, Luxembourg.
authors.forename: Mahesh S
authors.initials: MS
authors.lastname: Desai
authors.affiliation: Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 6 avenue du Swing, Belvaux L-4367, Luxembourg.
authors.forename: Kacy
authors.initials: K
authors.lastname: Greenhalgh
authors.affiliation: Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 6 avenue du Swing, Belvaux L-4367, Luxembourg.
authors.forename: Audrey
authors.initials: A
authors.lastname: Frachet
authors.affiliation: Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 6 avenue du Swing, Belvaux L-4367, Luxembourg.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Niegowska
authors.affiliation: Center for Applied Nanobioscience and Medicine, University of Arizona, 145S 79th Street, Suite 16, Chandler, Arizona 85226, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Estes
authors.affiliation: Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 6 avenue du Swing, Belvaux L-4367, Luxembourg.
authors.forename: Christian
authors.initials: C
authors.lastname: Jäger
authors.affiliation: Department of Infection and Immunity, Luxembourg Institute of Health, 29 rue Henri Koch, Esch-sur-Alzette L-4354, Luxembourg.
authors.forename: Carole
authors.initials: C
authors.lastname: Seguin-Devaux
authors.affiliation: Center for Applied Nanobioscience and Medicine, University of Arizona, 145S 79th Street, Suite 16, Chandler, Arizona 85226, USA.|Department of Basic Medical Sciences, University of Arizona, 425N. 5th Street, Phoenix, Arizona 85004, USA.
authors.forename: Frederic
authors.initials: F
authors.lastname: Zenhausern
authors.affiliation: Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 6 avenue du Swing, Belvaux L-4367, Luxembourg.
authors.forename: Paul
authors.initials: P
authors.lastname: Wilmes
mesh_terms: D000332:Aerobiosis; D000693:Anaerobiosis; D001419:Bacteria / Q000166:cytology; D018938:Caco-2 Cells; D018920:Coculture Techniques; D000069196:Gastrointestinal Microbiome; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D055432:Metabolomics; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D044085:Microfluidics / Q000379:methods*; D008954:Models, Biological; D015203:Reproducibility of Results
chemical_list: D035683:MicroRNAs