Scientists at Harvard's Wyss Institute have been working on human "organs-on-a-chip" technology in order to pioneer new therapies and predict drug safety in the lab. Now a team at the institute has leveraged their technology to engineer a model of human intestinal inflammation and bacterial overgrowth in a human "gut-on-a-chip."
The Wyss Institute for Biologically Inspired Engineering launched in 2009 as a $125 million gift by Hansjörg Wyss to Harvard University--the largest single philanthropic donation in its history. The overarching goal of their human organs-on-a-chip project was to eventually replace animal models with a device to model human diseases.
Inflammatory bowel disease (IBD) is caused and worsened by a combination of the gut's bacteria known as the microbiome, intestinal epithelial cells, immune cells and the gut's natural muscular movements. Until now, our knowledge of the disease and drug development has been lacking due to the difficulty in reproducing these contributing factors in the lab.
The team, led by the founding director of the Wyss Institute, Donald Ingber, and a faculty member, James Collins, published their work in the Proceedings of the National Academy of Sciences.
The human gut-on-a-chip was first developed at the institute in 2012 and comprises a clear flexible polymer the size of a computer USB stick. The device contains a hollow channel to mimic a tiny section of the gut, which the researchers say allows the physical structure, microenvironment and fluidic movements of the human gut to be recapitulated in the lab.
They report that intestinal cells and living microbes from a normal and diseased human gut can be co-cultured for up to two weeks, providing sufficient time to understand the pathology of IBD.
"The discovery of the microbiome and its significance represents a huge paradigm shift in our understanding of human health--there are more microbes living on us and in us than our own cells," Ingber said. "Until now, use of traditional culture methods and even more sophisticated organoid cultures have prevented the microbiome from being studied beyond one or two days."
Collins adds: "There is much to be learned about IBD, as well as how antibiotics impact the microbiome. This technology enables one to study in an isolated and controlled manner the complexity of the microbiome and the role different microbial species play in health and disease. It is therefore a highly valuable platform for discovery and clinical translation efforts."
Two findings have already sprouted from the technology--they've found four inflammatory proteins called cytokines to be produced together in the IBD model, creating inflammatory immune responses that may be responsible for damaging the bowel. With their gut-on-a-chip they also found that an absence of the natural muscular (known as peristaltic) movements of the bowel could create an overgrowth of bacteria--potentially explaining why after intestinal surgery IBD patients develop bacterial overgrowth when their normal peristaltic motions are delayed.
In the era of precision medicine, this may represent a significant finding to understand more about gut health and disease as well as testing drugs for more personalized medicine.