New invention makes it possible to study gut bacteria

Normally, researchers grow bacteria in the lab. But gut bacteria are highly sensitive to oxygen and notoriously difficult to keep alive under standard laboratory conditions. This makes them nearly impossible to study using conventional methods.

To overcome this, the team developed a model that supports the growth of oxygen-sensitive — or anaerobic — bacteria alongside living gut cells. The model contains two separate channels: one with oxygen, where gut cells can thrive, and one without, where the anaerobic bacteria can survive. In this way, the system replicates the two sides of the intestinal wall found in the human gut.

– Gut bacteria have evolved over millions of years to thrive in the low-oxygen environment of the intestine. But when exposed to oxygen, they die immediately — the complete opposite of us humans, who depend on oxygen to survive, explains Thomas Emil Andersen, professor of microbiology at the Department of Clinical Research.

- The opposite requirements of the human intestinal cells and the anaerobic bacteria make it very difficult to simulate the infections caused by these bacteria.

A mini gut in the lab

To solve this, doctors from OUH, microbiologists, engineering students and lab technicians from SDU joined forces. The outcome is a chip no larger than a mobile phone, equipped with a deoxygenation unit and a flow chamber where gut cells and bacteria grow together.

The model is a result of close interdisciplinary collaboration. Because how do you create an environment where both gut cells and anaerobic bacteria can live side by side? And how do you mimic the complex conditions inside the human intestine?

To make the model work, the team had to develop a special device that rapidly removes oxygen from the liquid surrounding the bacteria. The invention is unique — and has already led to two patent applications.

Broad potential for future use

Although the key technical hurdles have been overcome, the team is still fine-tuning the system.

– We have reached the point where we have demonstrated proof of concept — showing that the idea works. The next step is to make the system useful in regular laboratories and for laboratory staff who aren't specialists like us, says Thomas Emil Andersen.

– Designing such a widely applicable system in a form and shape that can be serially produced, is the main aim of the project at this phase. This way the system can assist the many researchers out there seeking to develop new treatments against the many pathologies associated with anaerobic microorganisms.

The model has already solved a mystery

For years, the anaerobic bacterium Clostridioides difficile has been a major challenge for clinicians and researchers alike. In patients treated with antibiotics, the bacterium can survive and remain in the gut, producing toxins that disrupt the gut flora, trigger inflammation, and increase both hospital stays and mortality rates.

The artificial gut model has already helped uncover why Clostridioides difficile infections tend to recur after treatment.

– The model has become a key tool in my research. It's a window into a biological world that was previously out of reach, says Line Lundegård Bang, co-inventor of the model and PhD student on the project.

– We’ve now seen that the bacterium forms a protective biofilm that helps it survive antibiotic treatment — which could explain why infections often return once treatment ends.

The researchers have also gained new insight into what triggers Clostridioides difficile to produce its harmful toxins. As such, the model helps explain the bacterium’s unique ability to cause infection and resist treatment — vital knowledge for developing more effective therapies in future.

– It’s incredibly motivating to work on a project that has real potential to generate knowledge and ultimately help the many vulnerable patients suffering from intestinal infections — especially those caused by Clostridioides difficile.