Engineered probiotic senses inflammation and helps repair the gut in mice

by Andrew Zinin, Medical Xpress

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edited by Lisa Lock, reviewed by Robert Egan

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Inflammatory bowel disease damages the lining that separates the gut's contents from the rest of the body. Calming the inflammation is only part of the treatment challenge, however—that protective barrier also needs to heal.

Researchers have engineered a probiotic bacterium that uses the chemical signs of inflammation to switch on production of a protein that encourages intestinal repair. Given orally to mice with chemically induced colitis, the bacteria both reduced tissue damage and promoted recovery of the gut lining.

Yu Zhao of Hunan University in China and colleagues describe their approach in the journal Cell Reports. Their experiments connect two promising treatment pathways of detecting an inflamed gut and delivering a repair signal in response.

Reading the signs of damage

The team started with Escherichia coli Nissle 1917, a bacterial strain used as a probiotic. They added a genetic switch that is responsive to reactive oxygen species, which are chemicals that accumulate in inflamed intestinal tissue.

To check whether the bacteria could detect inflammation, the researchers connected the switch to instructions for making a light-generating enzyme. After mice received the bacteria orally, laboratory measurements of their stool showed stronger light signals as inflammation developed.

The signal was associated with the severity of tissue damage, rather than simply with the number of bacteria present. That suggested the microbes could report changes in the gut's condition.

The team also mixed the sensor bacteria with stool samples from eight people with inflammatory bowel disease and eight healthy volunteers. After six hours, samples from the disease group produced stronger signals.

Detecting damage was the first task; the next was giving the bacteria something useful to do when they found it.

From an alarm to a repair signal

The researchers chose interleukin-22, or IL-22, a signaling protein that encourages cells lining the intestine to regenerate. They used a modified form called IL-22-Fc, which has a longer half-life and is designed to last longer.

Before linking production to the inflammation sensor, the team tested bacteria that made the protein continuously. Across several mouse models of colitis, these bacteria reduced intestinal damage compared with control bacteria that lacked the therapeutic instructions.

One experiment tested whether the lining actually became a better barrier. The researchers gave mice a fluorescent tracer and measured how much escaped the intestine to enter the bloodstream. Lower levels of the tracer were measured in the blood of treated mice, indicating that the gut was less leaky. The treatment failed to improve healing in mice that lacked the receptor that recognizes IL-22. This supported the explanation that the bacteria's protein was working through the intended repair pathway.

The version of the bacteria that continuously produced the protein also reduced damage in piglets with chemically induced colitis. Colonoscopy and tissue examinations showed better-preserved intestinal structure. The experiment was small, however, as there were only three piglets in each group.

The team then connected protein production to the inflammation-responsive switch, replacing the light-producing instructions with those for making IL-22-Fc. In a separate mouse experiment, oral treatment reduced tissue injury and also increased markers of cell growth and barrier repair.

The authors describe the approach as "localized, on-demand production of IL-22-Fc." The distinction matters—the engineered bacteria respond to a chemical cue inside the gut, rather than relying solely on a schedule for producing the protein.

Whether that kind of control can support safe, effective treatment in people remains untested, and the small stool-sample experiment does not establish a clinical diagnostic test. The next challenge for the researchers is to determine whether bacteria can deliver enough repair protein, in the right places and for long enough, to help a human gut heal.

Written for you by our author Andrew Zinin, edited by Lisa Lock, and fact-checked and reviewed by Robert Egan—this article is the result of careful human work. We rely on readers like you to keep independent science journalism alive. If this reporting matters to you, please consider a donation (especially monthly). You'll get an ad-free account as a thank-you.

Publication details

Yu Zhao et al., An engineered probiotic for diagnosis and mucosal healing in inflammatory bowel disease, Cell Reports (2026). DOI: 10.1016/j.celrep.2026.118171

Journal information: Cell Reports

Key medical concepts

Escherichia coli strain Nissle 1917Reactive Oxygen Species

Clinical categories

GastroenterologyDigestive healthClinical pharmacology Who's behind this story?

Andrew Zinin

Master's in physics with research experience. Long-time science news enthusiast. Plays key role in Science X's editorial success. Full profile →

Lisa Lock

BA art history, MA material culture. Former museum editor, paramedic, and transplant coordinator. Editing for Science X since 2021. Full profile →

Robert Egan

Bachelor's in mathematical biology, Master's in creative writing. Well-traveled with unique perspectives on science and language. Full profile →

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