A 3D Bioprinted Gut Anaerobic Model for Studying Bacteria–Host Interactions
Liqin Cheng,
Tingting Liu,
Qiong Liu,
Liming Lian,
Guosheng Tang,
Luis Santiago Mille,
Fabricio Romero García,
Lars Engstrand,
Yu Shrike Zhang,
Juan Du
Affiliations
Liqin Cheng
Centre for Translational Microbiome Research (CTMR), Department of Microbiology, Tumor, and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Tingting Liu
Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, 65 Landsdowne Street, Cambridge, MA 02139, USA.
Qiong Liu
Liming Lian
Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, 65 Landsdowne Street, Cambridge, MA 02139, USA.
Guosheng Tang
Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, 65 Landsdowne Street, Cambridge, MA 02139, USA.
Luis Santiago Mille
Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, 65 Landsdowne Street, Cambridge, MA 02139, USA.
Fabricio Romero García
Centre for Translational Microbiome Research (CTMR), Department of Microbiology, Tumor, and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Lars Engstrand
Centre for Translational Microbiome Research (CTMR), Department of Microbiology, Tumor, and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Yu Shrike Zhang
Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, 65 Landsdowne Street, Cambridge, MA 02139, USA.
Juan Du
Centre for Translational Microbiome Research (CTMR), Department of Microbiology, Tumor, and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
The role of the human intestinal tract in host–microbe interactions has been highlighted in recent years. Several 3-dimensional (3D) models have been developed to reproduce the physiological characteristics of the human gut and to investigate the function of the gut microbiota. One challenge for 3D models is to recapitulate the low oxygen concentrations in the intestinal lumen. Moreover, most earlier 3D culture systems used a membrane to physically separate bacteria from the intestinal epithelium, which has sometimes made the studies of bacteria adhering to or invading cells less feasible. We report the establishment of a 3D gut epithelium model and cultured it at high cell viability under an anaerobic condition. We further cocultured intestinal bacteria including both commensal and pathogen directly with epithelial cells in the established 3D model under the anaerobic condition. We subsequently compared the gene expression differences of aerobic and anaerobic conditions for cell and bacterial growth via dual RNA sequencing. Our study provides a physiologically relevant 3D gut epithelium model that mimics the anaerobic condition in the intestinal lumen and supplies a powerful system for future in-depth gut–microbe interactional investigations.
