For decades, peering into the gut meant invasive procedures and partial answers. Now, scientists are developing a biosensor that could reveal a far more expansive picture of what’s really happening deep inside.
Researchers at the University of British Columbia have developed a new biosensor in preclinical models that provides noninvasive, continuous monitoring through stool samples. Their paper, titled “A Bacteroides synthetic biology toolkit to build an in vivo malabsorption biosensor,” was published in Cell and describes how diagnostics concerning the gut could be improved by harnessing the bacteria that already reside there.
“Beneficial bacteria that naturally reside in the intestine and support gut health are highly sensitive to local conditions and have evolved to thrive long-term in these environments,” said first co-author Giselle McCallum, PhD. “Building biosensors in these bacteria, therefore, allows researchers to continuously monitor the gut environment without disturbing it.”
The team used Bacteroides thetaiotaomicron (B. theta), a native gut bacterium, where they identified genes that are activated in response to gut disruptions, such as in gastrointestinal diseases like celiac and inflammatory bowel disease. One disruption, osmotic stress, or when the gut is unable to absorb food properly, causes a buildup of undigested molecules, drawing water into the bowel, which can lead to a variety of gut-related symptoms. Examples include diarrhea and inflammation, as well as a worsening prognosis of the disease.
“Understanding these gut changes is essential for advancing our diagnostic and treatment strategies for gut health,” said senior author Carolina Tropini, PhD, assistant professor in the department of microbiology and immunology (MBIM) and the school of biomedical engineering. “For that, we need highly sensitive measurements as those changes occur, including before symptoms appear.”
Instead of taking a traditional route of engineering the bacteria to glow when stressed, the researchers noticed that B. theta’s glow was too weak to detect and decided to invert the system, where the bacteria would glow brightly under normal conditions and dim when under stress. They reasoned that higher osmotic stress (leading to malabsorption) would result in a weaker glow, allowing researchers to measure stress based on how much the signal dims.
The team applied their biosensor approach in mice and analyzed stool samples by measuring the intensity of the glow in individual bacterial cells. “We found that the biosensor accurately reported osmotic stress in the gut, even picking up subtle changes that didn’t cause clinical symptoms like diarrhea. It remained stable and responsive for weeks, which means it could track the gut environment long-term and potentially detect illness before symptoms develop,” co-first author Juan Camilo Burckhardt, a PhD candidate in the department of MBIM, said in a statement.
Burckhardt added, “Our biosensors could improve the ability to predict how diseases in the gut progress, identifying early changes that could aid preventative interventions.”
“While early applications will likely focus on monitoring gastrointestinal diseases, the long-term goal is a personalized approach where people can track aspects of their gut health over time and identify early warning signs of imbalance or dysfunction,” said Tropini. The same sensors mapping gut health in preclinical models today could one day help guide the clinical decisions of tomorrow, with a more personalized approach.
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