Engineered calprotectin-sensing probiotics for IBD surveillance in humans

Area of Science:

• Synthetic Biology
• Gastroenterology
• Microbiome Engineering

Background:

• Inflammatory bowel disease (IBD) involves chronic gut inflammation with unpredictable flares.
• Current IBD monitoring via endoscopy is invasive and requires specialized medical expertise.
• Synthetic biology offers potential for engineered microbes to detect disease biomarkers.

Purpose of the Study:

• To engineer a probiotic bacterium to detect calprotectin, a gold standard biomarker for IBD.
• To assess the engineered probiotic's ability to identify active IBD in patients noninvasively.

Main Methods:

• Identified a calprotectin-responsive bacterial promoter in *Escherichia coli* Nissle 1917 (EcN).
• Engineered EcN as a reporter strain for calprotectin detection.
• Validated the engineered probiotic in murine colitis models and human stool samples.

Main Results:

• The engineered probiotic demonstrated specific reporter gene expression in the presence of calprotectin.
• In vivo studies showed reporter signal activation in murine models of colitis.
• The probiotic accurately discriminated between active IBD patients, those in remission, and healthy individuals using stool samples, with signal intensity correlating with calprotectin levels.

Conclusions:

• Engineered probiotics can be developed to detect calprotectin, a key IBD biomarker.
• This approach enables precise, noninvasive monitoring of IBD disease activity.
• The study paves the way for novel diagnostic tools for IBD management.