Smart therapeutics: Bioengineers create non-invasive biosensor to detect gut disease

18 Aug 2023 --- Bioengineers from Rice University, US, have created a platform that allows engineered biosensor bacteria safe passage through the gastrointestinal (GI) tract. Probiotics such as these – engineered to sense and report signs of bowel inflammation – could be the future of non-invasive gut disease detection.

The bioengineers combined synthetic biology with biomaterial design to create a platform that could eventually monitor disease progression, assess treatment response and provide customized care for the individual gut microbiome.

“For our proof-of-concept study, we chose inflammatory bowel disease (IBD), an autoimmune disorder that causes painful and recurrent inflammation flares. But gut health plays many important roles in the human body, affecting metabolism, immunity, brain function and other systems,” says Elena Musteata, a graduate student in systems, synthetic and physical biology, Tabor lab, Rice University.

“As we discover more biomarkers for different diseases, we can use this platform to diagnose and monitor many health conditions.”

The engineered bacterial strain produces a fluorescent green protein in response to thiosulfate, a compound associated with gut inflammation. It makes it possible to assess colon inflammation by measuring bacterial fluorescence after passage through the animal GI tract.

Replacing invasive diagnostics
Once clinically proven, the method could provide firsthand information about the inner workings of the intestines, provided they are not killed or dispersed in the process. The platform could replace the prolonged and complex diagnostic process for IBD, which involves invasive, time-consuming procedures like colonoscopies and biopsies. 

The “good” bacteria, designed to produce a fluorescent protein in response to physiological signs of disease, fared well inside the gut of the test rat, protected inside alginate particles. The platform appears viable to improve patient outcomes because of its ability to tailor treatments to individual patient’s physiology.The platform could replace invasive and complex diagnostics procedures to analyze the gut.

The study’s findings demonstrating how the platform works were published in Biomaterials and ScienceDirect. The researchers are currently working toward making this scenario a clinical reality.

“If, in the future, we encapsulate a diverse range of biosensor strains, we could get an idea about a specific person’s inflammatory profile and then use that information to develop a more personalized diagnosis and treatment,” says Samira Aghlara-Fotovat, a bioengineering graduate student in the Veiseh lab and first author of the study.

Meanwhile, a growing body of research is evidencing the potential of probiotics – dubbed psychobiotics – as an alternative to antidepressants.

Promise of a quicker diagnosis
While it’s not new for bacteria to be genetically programmed to detect disease biomarkers in the GI tract, they face survival challenges in harsh conditions of low pH, destructive enzymes and bile salts. Free bacteria can disperse widely in the gut, making analysis more complex and potentially less accurate.

“With our system, patients could theoretically receive a prescription for the capsules and simply drop off a stool sample after ingestion, eliminating the need for repeated colonoscopies or biopsies,” says Aghlara-Fotovat. 

“Monitoring disease progression over time or tracking how a patient responds to a given therapy could be much more accessible using a platform like this.”

The study supporting the new platform demonstrated that encapsulating biosensor bacteria in protective alginate particles enables their robust survival and diagnostic function in living animals. The researchers characterized the effect of encapsulation on the viability, population dynamics and performance of a thiosulfate-sensing bacterial strain previously developed in the lab.

Encapsulation offers several advantages for intestinal biosensing with engineered bacteria. Because capsules are macroscopic, they can be more easily identified and analyzed than free bacteria. Bacteria are spatially concentrated within the capsules; therefore, their reporter gene expression is easier to visualize than in the same number of free bacteria. 

Encapsulation can protect bacteria from environmental hazards helping researchers to improve the survival of probiotic E. coli under acidic conditions.

“It’s very important to minimize the delay between symptom onset and treatment. Having a way to assess gut health within a short time and then take action could generate a significant advance in the clinical management of chronic inflammation and other gut-related disorders,” says Musteata.

“Even ten years ago, this idea of engineered probiotics acting as small diagnostic robots that could travel inside your body and detect your disease state was largely in science fiction. However, groups at Rice University and numerous other institutions are making real progress toward deploying this technology,” Musteata concludes.

By Inga de Jong