In the battle against intestinal disease, our bodies employ multiple lines of defense to keep harmful bacteria at bay. While most of us never think about these protective mechanisms, people with Crohn’s disease experience what happens when these defenses fail. Now, research reveals a critical missing piece in understanding Crohn’s disease: a protein called MUC17 that forms an essential protective barrier in the small intestine.
Scientists from the University of Gothenburg in Sweden and the University of British Columbia in Canada have discovered that MUC17, a mucin protein that creates a barrier called the glycocalyx, is significantly reduced in Crohn’s disease patients. This reduction allows bacteria to make direct contact with intestinal cells, potentially triggering the inflammation characteristic of the condition.
The glycocalyx is an invisible shield covering the cells that line our intestines. When this shield is compromised, as it appears to be in Crohn’s disease, bacteria that should remain at a safe distance can directly interact with intestinal cells, initiating inflammatory responses that damage the gut.
“By reinforcing the gut’s protective barrier, we might prevent bacteria from invading the epithelial cells that line the intestine, which could halt both the onset and progression of the disease,” says Thaher Pelaseyed, Associate Professor at Sahlgrenska Academy, University of Gothenburg, in a statement.
Crohn’s disease affects roughly 1.6 million Americans and millions more worldwide. Globally, it’s estimated to affect up to 300 per 100,000 people, with the highest prevalence in North America and Europe. The condition causes chronic inflammation anywhere along the digestive tract but most commonly affects the terminal ileum, the end portion of the small intestine. Unlike ulcerative colitis, which is limited to the colon, Crohn’s can create patchy areas of inflammation throughout the digestive system. Symptoms often include bloody diarrhea, abdominal pain, weight loss, and malnutrition, though complications outside the intestine can also occur.
To understand how MUC17 functions, the researchers developed a mouse model lacking this protein specifically in intestinal cells. These mice showed no obvious problems under normal conditions but became vulnerable when exposed to bacteria.
When exposed to Citrobacter rodentium, a bacterium that normally infects only the mouse colon, mice lacking MUC17 surprisingly developed infections in their small intestine—a part of the gut that should typically resist this pathogen. The bacteria were able to penetrate the protective barriers and directly contact the intestinal cells, something that didn’t happen in normal mice with intact MUC17.
This mirrors what the researchers observed in human Crohn’s disease patients, whose intestinal tissue samples showed bacteria making direct contact with the intestinal lining—something that rarely occurs in healthy individuals.
Even under normal conditions without any experimental infection, mice lacking MUC17 showed signs of damage to their intestinal lining. They had increased cell death at the tips of intestinal villi (the finger-like projections that increase the surface area of the intestine) and abnormally high rates of cell growth in the crypts (the valleys between villi where new intestinal cells are born).
The absence of MUC17 allowed bacteria to escape the gut entirely. The researchers found living bacteria in the lymph nodes, spleen, and other tissues of mice lacking MUC17—a sign that the intestinal barrier had failed at its basic job of keeping bacteria contained within the gut.
The mice lacking MUC17 developed enlarged fat deposits around their intestines, similar to the “creeping fat” seen in Crohn’s disease patients. They also became heavier overall compared to normal mice, suggesting body-wide metabolic changes resulting from bacterial escape from the gut.
A key finding from this research and a complementary study is that the reduction in MUC17 levels is not due to decreased production of the protein but rather to disrupted transport and stability within the intestinal cells. The team identified three key proteins—MYO1B, MYO5B, and SNX27—that are essential for positioning and stabilizing MUC17 on the surface of the epithelial cells. When these processes fail, the protective barrier is impaired, allowing bacteria to invade intestinal tissue more easily.
“Understanding how MUC17 is transported within intestinal epithelial cells to ultimately form the protective glycocalyx on the cell surface allows us to identify new drug targets that repair the glycocalyx barrier in Crohn’s disease. This approach could reduce the need for traditional anti-inflammatory treatments, which often have limited efficacy and carry a risk of resistance,” explains Pelaseyed.
Current treatments for Crohn’s disease primarily focus on dampening the inflammatory response after it has already started. These include anti-inflammatory drugs, immunosuppressants, and biologic therapies that target specific components of the immune system. While effective for many patients, these treatments can have significant side effects and don’t address the root causes of the disease.
A therapy targeting MUC17 or the glycocalyx barrier would represent a different approach—addressing one of the earliest defects in the disease process rather than just managing its consequences. Such treatments could potentially be more effective and have fewer side effects than current options.
The research also highlights the importance of regional differences in the gut’s defense systems. While MUC17 proved critical for small intestinal protection, it seemed less important in the colon. This makes sense given that the small intestine and colon have different architecture and defense mechanisms.
The results propose a new approach to treat Crohn’s disease by strengthening the gut’s natural defenses rather than merely treating symptoms. This perspective shift could open new therapeutic avenues for a condition that continues to challenge medical science.
Paper Summary
Methodology
The research team used both human samples and lab mice to study MUC17’s role in gut health. They analyzed tissue samples from Crohn’s disease patients and people without inflammatory bowel disease, measuring MUC17 levels and testing how bacteria interact with the intestinal surface. They also created mice lacking the Muc17 gene in their intestinal cells. These mice were exposed to various challenges, including bacterial infection, to see how they responded without the protection of MUC17. Using advanced microscopy, the researchers could see the protective barrier and watch how bacteria interacted with intestinal cells. They also analyzed which proteins were present and what types of bacteria lived in the gut, connecting their findings from humans with what they observed in mice.
Results
In people with Crohn’s disease, MUC17 levels in the small intestine were much lower than in people without the disease, while another similar protein remained unchanged. Bacteria made more frequent contact with the intestinal surface in Crohn’s disease samples. In mice lacking Muc17, the protective sugar coating in the small intestine was reduced. When exposed to bacteria, these mice developed unusual small intestinal infections, with bacterial counts in the middle section of the small intestine a thousand times higher than in normal mice. Even without any deliberate infection, mice without Muc17 showed increased bacteria touching intestinal cells, more cell growth, and more cell death—all signs of barrier problems. Most notably, these mice had living bacteria in their lymph nodes, spleen, and liver, along with increased abdominal fat similar to what’s seen in Crohn’s disease. The types of bacteria in their intestines were also altered in ways that resemble changes seen in Crohn’s disease patients.
Study Limitations
The study has several limitations to keep in mind. The human sample size was relatively small, with tissue samples from 16 people without inflammatory bowel disease and 9 Crohn’s disease patients. All samples were from non-inflamed areas, so the study doesn’t show how MUC17 levels might change during active inflammation. The mouse model differs from human physiology—mouse Muc17 is found in both small intestine and colon, while human MUC17 is only in the small intestine. The study also doesn’t clarify whether MUC17 deficiency causes Crohn’s disease or results from it. Additionally, while the researchers observed changes in gut bacteria, they didn’t fully explore how these microbial changes might contribute to disease development.
Key Takeaways and Discussion
The research shows that MUC17 is essential for small intestinal defense, particularly in keeping bacteria from touching the gut lining. The findings suggest that problems with this protective barrier may occur before inflammation begins in Crohn’s disease, potentially representing one of the earliest defects in the disease. The region-specific function of MUC17 helps explain why certain parts of the intestine are more vulnerable to Crohn’s disease than others. The study links MUC17 deficiency with altered bacterial communities and bacterial movement beyond the gut. The researchers suggest that reduced MUC17 leads to increased bacteria-cell contact, triggering inflammation and allowing bacteria to escape from the gut. This provides a new way of understanding Crohn’s disease and suggests new treatment approaches focused on restoring barrier function rather than just reducing inflammation.
Funding and Disclosures
The research was supported by multiple funding sources, including the Swedish Society for Medical Research, National Institutes of Health, and various foundations. One of the researchers, Bruce A. Vallance, holds the Children with Intestinal and Liver Disorders Foundation Chair in Pediatric Gastroenterology. The authors declared no conflicts of interest, and the study was published as an open-access article.
Publication Information
The study, titled “MUC17 is an essential small intestinal glycocalyx component that is disrupted in Crohn’s disease,” was published in JCI Insight in 2025. The research team was led by Elena Layunta, Bruce A. Vallance, and Thaher Pelaseyed, with contributions from several colleagues. The study originated from the University of Gothenburg in Sweden and the BC Children’s Hospital Research Institute at the University of British Columbia in Canada.