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Lab chip models gut microbiome diversity

Intestine-on-a-chip device cultures both aerobic and anaerobic bacteria, could help researchers study how drugs interact with gut microbes

by Celia Henry Arnaud
May 15, 2019 | A version of this story appeared in Volume 97, Issue 20


A micrograph showing bacterial cells (yellow) on top of intestinal epithelial cells.
Credit: Wyss Institute at Harvard University
Human gut bacteria (yellow) attach to a dense mucus layer produced by the intestinal epithelium created in a new chip. The smallest bacteria in this image are about 2 μm.

The human gut microbiome includes many types of bacteria that thrive in a variety of conditions. Some need oxygen—as do human cells—and others can’t tolerate high oxygen levels. Coming up with an experimental system that can mimic the human gut and meet the needs of both aerobic and anaerobic bacteria, as well as the host human cells, has been difficult. Such a device could help researchers study the interactions between gut microbes and our intestines, as well as understand how drugs interact with these bacteria.

“The challenge we all face in trying to build models that study the interface of gut bacteria and eukaryotic cells is providing an environment where both can thrive,” says Robert A. Britton, a microbiologist at Baylor College of Medicine.

A team led by Donald E. Ingber of the Wyss Institute for Biologically Inspired Engineering at Harvard University, has now developed a device that does just that. Ingber and his colleague have developed a microfluidic intestine-on-a-chip that can sustain aerobic and anaerobic bacteria in the same device (Nat. Biomed. Eng. 2019, DOI: 10.1038/s41551-019-0397-0).

The 2-channel device has vascular endothelial cells in the lower channel. The upper channel has human intestinal epithelial cells that form fingerlike villi reminiscent of structures in the small intestine. Separating the two channels is a porous membrane coated with extracellular matrix, which mimics the biological scaffold that supports the two types of cells in our guts. Perfusing oxygenated cell-culture medium through the endothelium-lined channel while housing the device in a nitrogen chamber, allows the researchers to maintain the desired oxygen gradient, running from 20% to <0.5% oxygen, to keep all the cells happy.

The researchers added bacteria from human stool samples to the upper channel and cultured everything together. The device sustained a diverse population of more than 200 types of microbes with an abundance of the bacteria reflecting what’s typically observed in human stool samples.

“Most of what we know about the microbiome in medicine is due to genomic and metagenomic analysis, which is really guilt-by-association and correlation,” Ingber says. The device is “a tool to get at what people are recognizing as being a previously unexplored part of medicine that can lead to new therapeutics and diagnostics,” he says.

But the device could be difficult for labs without microfluidics expertise to use, Baylor’s Britton says. Nonetheless, the work “provides an important proof of concept for long-term cultivation of microbes and epithelial cells that will help inform the development of other, more accessible, model systems,” Britton says.



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