The gastrointestinal tract is lined with a dense mucus layer that serves as both a physical barrier and an active interface between the body and trillions of microbes. While this barrier has long been understood as a passive shield, growing evidence suggests it is dynamically reinforced by proteins that respond to microbial threats. New research from the Massachusetts Institute of Technology adds important clarity to this picture by identifying how a naturally occurring protein helps both stabilize the mucus layer and neutralize invading bacteria.
The work was led by Laura Kiessling, Novartis Professor of Chemistry at MIT, with Amanda Dugan and Deepsing Syangtan as lead authors. While earlier studies had hinted at a role for intelectins in immune defense, direct experimental evidence for intelectin-2’s function had been limited. This study provides molecular-level insight into how the protein operates under both healthy and inflamed conditions.
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
The protein, known as intelectin-2, belongs to a broader class of carbohydrate-binding proteins called lectins, which are distributed across mucosal surfaces throughout the body. Lectins recognize specific sugar molecules on cell surfaces, allowing them to distinguish between host tissue and microbes. MIT researchers show that intelectin-2 plays a dual role in gastrointestinal defense, acting both as a structural stabilizer and as a broad-spectrum antimicrobial agent.
Laura Kiessling, Novartis Professor of Chemistry at MIT 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.”
Using biochemical assays and microbial growth experiments, the researchers demonstrated that intelectin-2 binds to galactose-containing carbohydrates. These sugars are abundant in mucins, the gel-forming molecules that give mucus its structure. By crosslinking these mucins, intelectin-2 reinforces the mucus layer, making it more resistant to physical disruption and microbial penetration.
The same carbohydrate-binding ability also allows intelectin-2 to recognize bacteria that display similar sugar patterns on their cell surfaces. When the mucus barrier is compromised—such as during inflammation—the protein can bind directly to these microbes, trapping them and limiting their growth. Over time, the researchers observed that some of the bound bacteria lost membrane integrity, suggesting that intelectin-2 can directly neutralize or kill them.
This antimicrobial activity appears to extend across a range of bacterial species, including pathogens commonly associated with gastrointestinal infections. Notably, some of the affected bacteria are known to exhibit resistance to conventional antibiotics, highlighting the potential relevance of this mechanism in the context of rising antimicrobial resistance.
The study also sheds light on how intelectin-2 expression differs between species and physiological states. In humans, the protein is produced at relatively steady levels by Paneth cells in the small intestine. In mice, however, intelectin-2 expression is more dynamic, increasing in response to inflammation or parasitic infection and originating primarily from mucus-secreting goblet cells. These differences suggest that intelectin-2 is part of a responsive defense system tuned to local immune conditions.
From an engineering and translational perspective, the findings raise several possibilities. In disorders such as inflammatory bowel disease, intelectin-2 levels are often dysregulated, either weakening the mucus barrier or excessively suppressing beneficial gut bacteria. Understanding how to modulate this protein’s activity could help restore balance in the gut microbiome while preserving protective functions.
More broadly, the work points toward a strategy for antimicrobial design that relies on reinforcing natural barriers rather than targeting microbes with traditional antibiotics. By mimicking or adapting lectin-based mechanisms, researchers may be able to develop therapies that reduce infection risk without driving resistance.
As interest grows in therapies that leverage the body’s innate defenses, intelectin-2 offers a clear example of how structural biology, microbiology, and bioengineering intersect at mucosal surfaces. Rather than acting as a single-purpose antimicrobial, the protein functions as part of a layered defense system—one that stabilizes the environment first and intervenes directly only when that barrier is breached.
In an era where maintaining microbial balance is increasingly seen as central to health, insights like these help move the field beyond simple pathogen elimination toward more nuanced, system-level approaches to disease prevention and treatment.
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).
