The human gut is home to a hundred trillion 'good' bacteria that are essential for it to function. But 'bad' bacteria can upset this balance, resulting in infection. US scientists have now found a way to mimic this environment in a lab-on-a-chip device, making it easier to investigate why some pathogenic bacterial strains are so virulent.

Communities of 'good' - or commensal - bacteria in the gut interact closely with the endothelial cells that line it. Up to now, studying these systems in vitro has been very difficult because bacteria multiply much faster than endothelial cells. Arul Jayaraman and colleagues at Texas A&M University, College Station, have now developed a microfluidic system that grows the colonies separately before allowing them to interact in a manner very similar to what happens in the gut. 

 

Good bacteria (green) and pathogenic bacteria (red) grow in an island separated from endothelial cells (grey) before they are allowed to mix to replicate conditions in the gut

The system consists of a polymer template that is lowered onto a glass surface to create an isolated island. The researchers seeded commensal Escherichia coli bacteria into the island, and endothelial cells outside, with nutrients allowed to flow in (and waste to flow out) through microfluidic channels. Once the colonies reached maturity, the team introduced a pathogenic strain of E. coli into the commensal colony, removed the template, and monitored the death of the endothelial cells as the pathogenic bacteria moved across the boundary.

Mike Shuler, Chair of Biomedical Engineering at Cornell University, Ithaca, US, says that 'this is a very clever microfluidic device. The work is an important first step to the broad problem of understanding bacterial interactions with the gastrointestinal tract.' He adds that it would be interesting to study cell types that produce mucus and hence more closely resemble those present in the gut. 

Jayaraman explains that the set-up is 'true to life' because it creates bacterial aggregates called biofilms rather than disorganised colonies. Previous studies, he says, have just added pathogenic bacteria into colonies of endothelial cells, which does not replicate the cellular interactions and chemical signals present in the gut. Their device, he says, will aid rapid screening of probiotic strains, such as those used as dietary supplements, because it allows the culture conditions for each strain to be optimised separately. 

David Barden 

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