Establishment of a Modular Anaerobic Human Intestine Chip

Sasan Jalili-Firoozinezhad; Amir Bein; Francesca S Gazzaniga; Cicely W Fadel; Richard Novak; Donald E Ingber

doi:10.1007/978-1-0716-1693-2_5

Establishment of a Modular Anaerobic Human Intestine Chip

Methods Mol Biol. 2022:2373:69-85. doi: 10.1007/978-1-0716-1693-2_5.

Authors

Sasan Jalili-Firoozinezhad^#¹, Amir Bein^#², Francesca S Gazzaniga^#^{2

3}, Cicely W Fadel^#^{2

4

5}, Richard Novak², Donald E Ingber^{6

7

8}

Affiliations

¹ Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
² Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
³ Department of Immunology, Harvard Medical School, Boston, MA, USA.
⁴ Department of Neonatology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
⁵ Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
⁶ Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA. don.ingber@wyss.harvard.edu.
⁷ Vascular Biology Program and Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA. don.ingber@wyss.harvard.edu.
⁸ Harvard John A. Paulson School of Engineering and Applied Sciences, Cambridge, MA, USA. don.ingber@wyss.harvard.edu.

^# Contributed equally.

PMID: 34520007
DOI: 10.1007/978-1-0716-1693-2_5

Abstract

It is impossible to analyze human-specific host-microbiome interactions using animal models and existing in vitro methods fail to support survival of human cells in direct contact with complex living microbiota for extended times. Here we describe a protocol for culturing human organ-on-a-chip (Organ Chip) microfluidic devices lined by human patient-derived primary intestinal epithelium in the presence of a physiologically relevant transluminal hypoxia gradient that enables their coculture with hundreds of different living aerobic and anaerobic bacteria found within the human gut microbiome. This protocol can be adapted to provide different levels of oxygen tension to facilitate coculturing of microbiome from different regions of gastrointestinal tract, and the same system can be applied with any other type of Organ Chip. This method can help to provide further insight into the host-microbiome interactions that contribute to human health and disease, enable discovery of new microbiome-related diagnostics and therapeutics, and provide a novel approach to advanced personalized medicine.

Keywords: Intestine; Microbiome; Microfluidic; Organ-on-a-Chip; Organoid; Oxygen gradients.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Anaerobiosis
Animals
Gastrointestinal Microbiome*
Humans
Intestinal Mucosa / metabolism
Lab-On-A-Chip Devices