PT  - JOURNAL ARTICLE
AU  - Sasan Jalili-Firoozinezhad
AU  - Francesca S. Gazzaniga
AU  - Elizabeth L. Calamari
AU  - Diogo M. Camacho
AU  - Cicely W. Fadel
AU  - Bret Nestor
AU  - Michael J. Cronce
AU  - Alessio Tovaglieri
AU  - Oren Levy
AU  - Katherine E. Gregory
AU  - David T. Breault
AU  - Joaquim M. S. Cabral
AU  - Dennis L. Kasper
AU  - Richard Novak
AU  - Donald E. Ingber
TI  - Complex human gut microbiome cultured in anaerobic human intestine chips
AID  - 10.1101/421404
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 421404
4099  - http://biorxiv.org/content/early/2018/09/20/421404.short
4100  - http://biorxiv.org/content/early/2018/09/20/421404.full
AB  - The diverse bacterial populations that comprise the commensal microbiota of the human intestine play a central role in health and disease, yet no method is available to sustain these complex microbial communities in direct contact with living human intestinal cells and their overlying mucus layer in vitro. Here we describe a human Organ-on-a-Chip (Organ Chip) microfluidic platform that permits control and real-time assessment of physiologically-relevant oxygen gradients, and which enables co-culture of living human intestinal epithelium with stable communities of aerobic and anaerobic human gut microbiota. When compared to aerobic co-culture conditions, establishment of a transluminal hypoxia gradient sustained higher microbial diversity with over 200 unique operational taxonomic units (OTUs) from 11 different genera, and an abundance of obligate anaerobic bacteria with ratios of Firmicutes and Bacteroidetes similar to those observed in human feces, in addition to increasing intestinal barrier function. The ability to culture human intestinal epithelium overlaid by complex human gut microbial communities within microfluidic Intestine Chips may enable investigations of host-microbiome interactions that were not possible previously, and serve as a discovery tool for development of new microbiome-related therapeutics, probiotics, and nutraceuticals.