Researchers at the Harvard Wyss Institute have developed a microfluidic chip that allows bacteria and human epithelial cells to be co-cultured. The device will allow researchers to study how the gut and bacteria interact, helping them to identify the role of the microbiome in health and disease.
With reported involvement in a huge array of diseases, including cancer, autoimmune diseases, infections and inflammatory diseases, the human microbiome is receiving increasing attention from researchers. However, one of the major hurdles in studying how the microbiome affects the body is the tendency of bacteria to quickly overwhelm and kill human cells when they are grown together in a cell culture dish. In addition, many of the bacteria that grow in the intestinal lumen are anaerobic, meaning they like to grow in low oxygen conditions, which also kill human cells.
“Earlier tissue culture systems that aimed at recapitulating interactions between the human microbiome and intestinal epithelial cells in vitro were limited in their usefulness because they could not grow the two components in direct contact to one another, and did not mimic the gut’s low oxygen concentrations crucial for the survival of anaerobic bacteria,” said Sasan Jalili-Firoozinezhad, a researcher involved in the study.
To address this, Jalili-Firoozinezhad and colleagues developed a microfluidic chip that makes co-culture possible. The chip contains two compartments separated by a porous membrane – one for a vascularized human intestinal epithelium culture, and another for a complex microbiome. By culturing the device in a custom anaerobic chamber, the researchers created an oxygen gradient whereby the human cells receive enough to grow and survive, but the bacteria are exposed to low oxygen conditions, which mimics the situation in the human intestine.
“We generated an oxygen gradient across the two channels that still allows the intestinal epithelium to be supported with oxygen diffusing through the porous membrane,” said Elizabeth Calamari, another researcher involved in the study. “In addition, we fitted the Intestine Chips with optical sensors that can report local oxygen concentrations in both channels in real-time without disturbing the oxygen gradient.”
The device hosted a huge diversity of bacteria, similar to that observed in the human microbiome, and the intestinal layer formed a protective mucus barrier, like the one in the human intestine. Given that the device appears to be a reasonable proxy for microbiome/gut interactions, the researchers hope that it could help with personalized medicine and identifying the role of the microbiome in a variety of diseases.
Here’s a video that shows how low oxygen conditions in the anaerobic Intestine Chip enable a complex human microbiome with bacteria that appear as tiny moving dots existing in direct contact with intestinal epithelial cells. Credit: Wyss Institute at Harvard University:
Study in Nature Biomedical Engineering: A complex human gut microbiome cultured in an anaerobic intestine-on-a-chip…