Research led by Laura Kiessling, Novartis Professor of Chemistry at the Massachusetts Institute of Technology, has identified a naturally occurring gastrointestinal protein that plays a dual role in protecting the gut from infection. The study examines intelectin-2, a carbohydrate-binding protein produced in the intestinal lining, and shows that it can both reinforce the mucus barrier of the gut and directly neutralize a wide range of bacteria.
Dugan, A. E., Syangtan, D., Nonnecke, E. B., Chorghade, R. S., Peiffer, A. L., Yao, J. J., Ille-Bunn, J., Sergio, D., Pishchany, G., Dhennezel, C., Vlamakis, H., Bae, S., Johnson, S., Ellis, C., Ghosh, S., Alty, J. W., Barnes, C. E., Krupkin, M., Cárcamo-Oyarce, G., … Kiessling, L. L. (2026). Intelectin-2 is a broad-spectrum antimicrobial lectin. Nature Communications, 17(1), 231. https://doi.org/10.1038/s41467-025-67099-4
Mucosal surfaces throughout the body rely on layered defense systems that combine physical barriers with molecular immune responses. In the gastrointestinal tract, mucus forms the first line of protection, limiting microbial contact with epithelial tissue. Embedded within this layer are lectins—proteins that recognize specific sugar structures on cells and microbes. While lectins are known for their role in immune recognition, their ability to act directly against microbes has remained unclear.
Laura Kiessling, Novartis Professor of Chemistry at the Massachusetts Institute of Technology stated,
“Harnessing human lectins as tools to combat antimicrobial resistance opens up a fundamentally new strategy that draws on our own innate immune defenses. Taking advantage of proteins that the body already uses to protect itself against pathogens is compelling and a direction that we are pursuing.”
The MIT team found that intelectin-2 functions through two related mechanisms. First, it binds to galactose-containing sugars present in mucins, the glycoproteins that make up intestinal mucus. By crosslinking these molecules, intelectin-2 increases the structural stability of the mucus layer. Experimental models showed that this interaction helps maintain barrier integrity, particularly under inflammatory conditions where mucus breakdown is more likely.
In addition to reinforcing mucus, intelectin-2 interacts directly with bacteria. Many gastrointestinal microbes display galactose-rich carbohydrates on their outer membranes, which serve as binding sites for the protein. Once attached, intelectin-2 restricts bacterial movement within the mucus layer. Over time, bound bacteria exhibited signs of membrane disruption and structural failure, indicating that the protein does more than immobilize microbes—it can actively compromise their viability.
The antimicrobial activity was observed across multiple bacterial species, including pathogens commonly linked to gastrointestinal infections. Some of these bacteria are known to exhibit resistance to conventional antibiotics, suggesting that intelectin-2 operates through a fundamentally different mechanism than traditional antimicrobial drugs.
Although intelectin-2 is produced continuously at low levels in the human small intestine, its expression patterns vary across species. In mice, for example, the protein is upregulated during intestinal inflammation and certain parasitic infections. Despite these differences, both human and mouse versions of intelectin-2 displayed similar carbohydrate-binding behavior, supporting the idea that its function is conserved.
The findings offer insight into disorders associated with mucus barrier dysfunction, including inflammatory bowel disease. Clinical studies have previously shown that intelectin-2 levels in IBD patients can fluctuate widely. Reduced levels may weaken mucus structure, while excessive levels could disrupt beneficial gut bacteria. The current work provides a molecular explanation for how imbalances in this protein could influence disease outcomes.
Beyond gastrointestinal health, the study contributes to broader efforts to address antimicrobial resistance by drawing on components of the innate immune system. Rather than targeting bacterial metabolism or replication directly, intelectin-2 reinforces the host’s physical defenses while selectively limiting microbial growth. This approach may inform the design of new therapeutics or biomaterials that stabilize mucosal barriers instead of relying solely on antibiotics.
As resistance to existing antimicrobial drugs continues to rise, research into multifunctional immune proteins such as intelectin-2 highlights alternative strategies rooted in the body’s own protective systems. By combining barrier reinforcement with direct antimicrobial action, intelectin-2 represents a model for future engineering approaches to infection control.
Adrian graduated with a Masters Degree (1st Class Honours) in Chemical Engineering from Chester University along with Harris. His master’s research aimed to develop a standardadised clean water oxygenation transfer procedure to test bubble diffusers that are currently used in the wastewater industry commercial market. He has also undergone placments in both US and China primarely focused within the R&D department and is an associate member of the Institute of Chemical Engineers (IChemE).
