Gain a deeper understanding of human host-microbiome interactions
The role of the microbiome in human health and disease remains poorly understood
Understanding the human gut microbiome is of critical importance given its role in immune system regulation, inflammatory bowel disease, cancer, and neuropsychiatric disorders. It is also known that the gut microbiome can influence drug absorption and metabolism. Unfortunately, no established in vitro model exists for co-culturing gut commensal microorganisms in direct contact with intestinal epithelium, and differences in animal model intestinal physiology and microbiome composition often limit their human relevance.
How we can help
Explore the human microbiome with Organ-on-a-Chip technology
With Organ-Chips, researchers can culture human intestinal cells in direct contact with human gut microbiota. The dynamic microenvironment of Organ-Chips has been shown to support a stable microbial co-culture, overcoming the challenge of bacterial overgrowth that often occurs within hours in conventional in vitro models. Organ-on-a-Chip technology could serve as a discovery platform for understanding the microbiome’s role in healthy and disease physiology and accelerating the development of microbiome-related therapies, probiotics, and nutraceuticals.
Investigate clinically relevant human host-microbiome interactions at the cellular and molecular level
Most of what we know about human-microbiome interactions is based on correlational studies between disease state and bacterial DNA, due to the challenges of modeling the microbiome in vitro. The Intestine-Chip enables researchers to co-culture a complex human microbiome in direct contact with primary intestinal epithelium over multiple days. Researchers can investigate the microbiome’s role in barrier function, explore the impact of shear forces and peristaltic-like cyclic stretch, and study the effect of drugs.
How Organ-Chips are being used
In research published in Nature Biomedical Engineering, the Wyss Institute used Organ-on-a-Chip technology to culture a stable, complex human microbiome for at least five days in anaerobic conditions.
By developing a proof-of-concept method for controlling oxygen levels, the team was able to provide appropriate oxygenation to the endothelial and epithelial cells while maintaining hypoxic conditions in the channel inhabited by the commensal bacteria. These low oxygen conditions are critical for the survival of anaerobic bacteria commonly found in the intestine.
Over 200 distinct groups of bacteria were sustained in culture over several days, maintaining the richness of microbial diversity found in the human intestine. Importantly, the complex microbiome enhanced the barrier function of the intestinal epithelium. The direct access to the microbiome and intestinal tissue offered by Organ-Chips opens the door to discover specific microbes or their metabolites that cause disease or that might help prevent these conditions.