Trillions of microbes live in our gut, helping to digest food, supporting the immune system, and fighting disease-causing bacteria. But bacteria may have another way to keep our guts healthy: by acting as living factories to make therapeutic drugs inside our bodies. Therapeutic bacteria are easy to produce and can live within our guts, where they can produce drugs that are released directly to the surrounding environment. Unlike traditional oral medication, therapeutic bacteria only need to be taken once, and then they can live within the gut and release their helpful products over a long period of time. The NIH Common Fund’s High-Risk High-Reward Research Program funds transformative research with the potential to develop new ways of improving health though unconventional approaches that challenge existing paradigms. A Transformative Research Award team at Massachusetts General Hospital led by Drs. Cammie Lesser, Wendy Garrett, and John Leong aims to create designer probiotic bacteria that can deliver drugs to specific targets within the body.

To tackle this challenge, the team of researchers modified a strain of naturally occurring probiotic E. Coli to produce and release anti-inflammatory proteins. These bacteria could establish themselves in the intestinal tract of mice without disturbing the native gut microbiome. The researchers found that giving a single dose of these modified bacteria to mice reduced the development of ulcerative colitis, a type of irritable bowel disorder. The bacteria worked as effectively as traditional anti-inflammatory drugs which impact the whole body and not just a targeted treatment area. The researchers concluded that the therapeutic bacteria would be safer than currently used oral treatments because they deliver drugs locally within the gut which reduces the exposure of anti-inflammatory drugs to the healthy tissues limiting unintended side effects.

These new bacteria can also be engineered to produce other types of drugs or helpful molecules that have the potential to target other kinds of tissues, including solid tumors. Overall, these therapeutic bacteria provide a drug delivery platform that already lives within and works with our bodies, offering new and transformative ways to treat diseases and reduce side effects.

Read more about the goals of Drs. Lesser, Garrett, and Leong’s Transformative Research Award. 

Reference: Lynch JP, González-Prieto C, Reeves AZ, Bae S, Powale U, Godbole NP, Tremblay JM, Schmidt FI, Ploegh HL, Kansra V, Glickman JN, Leong JM, Shoemaker CB, Garrett WS, Lesser CF. Engineered Escherichia coli for the in situ secretion of therapeutic nanobodies in the gut. Cell Host Microbe. 2023 Apr 12;31(4):634-649.e8. doi: 10.1016/j.chom.2023.03.007.