Inflammatory bowel disease (IBD) affects millions of people worldwide, causing severe symptoms that are difficult to diagnose and monitor (often requiring invasive and expensive methods such as colonoscopy or endoscopy). Genetically engineered gut bacteria are a highly promising alternative that can persist in the gastrointestinal tract (GI) and sense and respond to specific environmental signals. Previously, engineered probiotics that could report biomarkers of gastrointestinal inflammation and other diseases generally relied on fluorescent or bioluminescent reporter genes. However, due to the poor penetration of light in tissues, the signals generated cannot be resolved in situ in vivo. The strategy relying on colorimetric reporter genes requires culturing feces. In view of this, Mikhail G. Shapiro from the California Institute of Technology has designed a probiotic biosensor that utilizes ultrasound technology for in vivo imaging.

Key points of this article:

(1) Ultrasound is a widely available and low-cost imaging method with sub millimeter spatial resolution that can penetrate deep into the human body. This biosensor is based on the clinically approved probiotic Escherichia coli Nissle. Researchers have genetically engineered it to colonize the gastrointestinal tract and sense inflammatory biomarkers, and it can respond by expressing air filled sound scattering protein nanostructures (bubble vesicles).

(2) After optimizing the biomolecule signaling pathway to achieve sensitive response to biomarkers thiosulfate and tetrathiosulfate and generate strong and stable ultrasound contrast, the researchers further demonstrated that the in vivo biosensor can achieve non-invasive imaging in antibiotic induced mouse inflammation models. In summary, the probiotic biosensor designed in this study can combine cell-based diagnostic probes with ultrasound technology, which is expected to provide a new method for more convenient and cost-effective diagnosis and monitoring of IBD and other gastrointestinal diseases.