Orally Administered Bacterial Biosensors Detect Gastrointestinal Disease in Mice

Researchers headed by a team at East China University of Science and Technology have developed a bacterial biosensor composed of tiny hydrogel-based microspheres packed with blood-sensing bacteria that can detect markers of gastrointestinal disease as they pass through the gastrointestinal tract. Taken orally, these miniature “pills” also contain magnetic particles that make them easy to collect from stool samples. Tests in a mouse model of colitis showed that the MagGel-BS (Magnetic hydroGel-encapsulated Bacterial biosensor) detected gastrointestinal bleeding within 20 minutes.

The researchers say the bacteria in the sensor could be adapted to detect other gut diseases. “This technology provides a new paradigm for rapid and noninvasive detection of gastrointestinal diseases,” commented Ying Zhou, PhD, at State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology. In their published paper in ACS Sensors, “Magnetic Hydrogel: Enhanced Bacterial Biosensor for Speedy Gut Disease Detection,” co-corresponding author Zhou and colleagues describe the development of the MagGel-BS platform and tests. In their report, the team stated, “In summary, this platform provides a rapid, noninvasive approach for gastrointestinal biomarker detection, demonstrating considerable potential for advancing bacterial-based diagnostics and therapeutics applications.”

Colorectal cancer or inflammatory bowel disease, including colitis, can cause intestinal bleeding, diarrhea, and cramping. As the authors noted in their paper, “Early and accurate diagnosis of gastrointestinal diseases is critical for timely intervention and effective symptom management.” The gold-standard diagnostic technique is colonoscopy using an endoscope, a device with a camera at the end of a long cord that is threaded into the large intestine. However, despite its clinical value, many people avoid the procedure because of the preparation involved and its invasiveness. “… traditional endoscopic methods, being invasive, often induce both physiological and psychological distress in patients and may lack the sensitivity required for early detection of intestinal diseases,” the team continued.

Zhou, Bang-Ce Ye, PhD, Zhen-Ping Zou, PhD, and colleagues are developing gentler methods using bacteria that sense disease biomarkers, such as the red blood cell component heme—a sign of intestinal bleeding. “Bacterial biosensors represent a promising avenue for detecting gastrointestinal disease biomarkers,” the team noted in the paper, “… however, their direct oral delivery is limited by challenges such as bioavailability, safety, and interactions with the complex gut microbiota.

Previously, the researchers had developed heme-sensing bacteria that light up in the presence of blood, but the bacterial sensors break down in the digestive system and are hard to collect. For their newly reported study, the team encapsulated the heme-detecting bacteria and magnetic particles inside a hydrogel “shell” composed of sodium alginate, a thickening agent used in foods. The process creates tiny hydrogel microsphere sensors that, after they have traveled through the body, can easily be removed from feces using a magnet. “The hydrogel shell serves as a protective barrier while creating a nutrient-rich environment that significantly enhances bacterial survival within the gastrointestinal tract,” the investigators explained.

Initial tests showed that the hydrogel protected the bacteria from simulated digestive fluids but also allowed heme to interact with the bacterial sensor, causing it to glow. Then, the team administered the microspheres orally to mouse models of colitis, representing disease levels from no activity to severe stages. After the microspheres traveled through the animals’ gastrointestinal systems, the researchers retrieved the sensors from feces with a magnet. Their experiments demonstrated that microsphere cleanup and signal analysis took about 25 minutes. The results showed that as the disease stage progressed, the intensity of the light produced by the sensor increased, which indicated more heme from mouse models with more advanced colitis. “Experimental models demonstrated the platform’s ability to maintain bacterial functionality and ensure precise detection,” they added.

Assessments of healthy mice given the sensor in addition indicated that the microspheres were biocompatible and safe. “… the hydrogel shell minimizes direct bacterial contact with host cells, enhancing biosafety, with no detectable immune responses or toxic effects observed on the gut microbiota of mice,” the team stated.

Although the sensor still needs to be tested in humans, the researchers say that this method of encapsulating bacterial sensors could diagnose gastrointestinal diseases and monitor treatments and disease progression. “In summary, this study presents an innovative platform, termed MagGel-BS, which effectively addresses critical challenges related to the targeted delivery and subsequent recovery of engineered bacteria within the gastrointestinal tract,” the team concluded.

They say the MagGel-BS platform represents a versatile framework for engineered bacterial delivery, with potential for broader application to other microbial sensors. “In summary, this platform provides a rapid, noninvasive approach for gastrointestinal biomarker detection, demonstrating considerable potential for advancing bacterial-based diagnostics and therapeutics applications.”