Modified Smart Microbes Could Treat Inflammatory Bowel Disease

Treating inflammatory diseases like inflammatory bowel disease (IBD) often involves systemic therapies that can lead to serious side effects due to their broad impact on the immune system. Patients typically receive large antibody drugs intravenously, which circulate throughout the body and may suppress immunity in areas beyond the target site. Now, researchers have developed an innovative solution using re-engineered bacteria that can deliver therapeutic proteins directly to the site of disease, offering a promising new route for safer, more targeted treatment.

The breakthrough comes from Tufts University School of Medicine (Boston, MA, USA), where scientists set out to repurpose the type III secretion system — a protein injection mechanism used by pathogenic bacteria — by moving a modified version into a probiotic strain of E. coli. This harmless gut-dwelling microbe was engineered to secrete nanobodies, a smaller form of therapeutic antibody, to reduce inflammation in patients with inflammatory bowel disease.

To make this work, the team first had to successfully transfer the complex secretion machinery — normally made up of about 25 components — into the probiotic strain and then redirect it to secrete nanobodies into the gut environment, rather than injecting them into host cells. After optimizing this novel system, the researchers tested it in mouse models and confirmed that the modified bacteria could release nanobodies at the site of inflammation in the digestive tract.

Unlike traditional antibody therapies, which require IV administration and can compromise immune function systemically, the nanobodies produced by the engineered bacteria act locally in the gut, where IBD symptoms are concentrated. This targeted approach not only improves therapeutic precision but also minimizes the risk of side effects such as infections caused by immune suppression. The engineered bacteria, named PROT3EcT (probiotic type III E. coli therapeutic), are designed to colonize the gut and continuously produce anti-inflammatory nanobodies at the site of disease.

Encouraged by these early findings, researchers are exploring other potential applications, including cancer treatment. Since certain bacterial strains are known to accumulate in tumors, the team hopes to adapt the system so that PROT3EcT could deliver tumor-killing proteins directly into cancerous tissue. While clinical use is still some way off, the researchers believe this approach could revolutionize how we use microbes to treat disease.

“We’re trying to figure out how to transform bacteria into therapeutic devices,” said Tufts physician-researcher Cammie Lesser who is using her knowledge to create a new way of delivering medicine.