New Insights into a Protein’s Role in Gut Health

Researchers have recently found that a specific protein in our gut plays a crucial role in fighting bacteria. This protein could potentially lead to effective treatments for conditions like inflammatory bowel disease in the future.

The protein, known as intelectin-2, has been around in the scientific community but its exact function within the gastrointestinal (GI) tract was somewhat unclear. Intelectin-2 belongs to a category of proteins called lectins, which interact with certain sugar molecules.

A team from MIT has now uncovered that intelectin-2 serves two key purposes. First, it connects mucus molecules that line the GI tract, which helps bolster the mucus barrier vital for safeguarding intestinal tissues.

However, if this barrier is compromised, intelectin-2 can identify and trap various bacterial cells, effectively inhibiting their growth or even destroying them. So, it operates both defensively and offensively, contributing to overall health.

“What’s fascinating is how intelectin-2 functions in these two complementary ways,” explains MIT chemist Laura Kiessling. “It stabilizes the mucus layer, and if that barrier is breached, it can neutralize or contain bacteria attempting to escape.”

The research team employed a variety of methods to assess the functions of intelectin-2. They examined mouse tissues, gut bacteria from both mice and humans, and isolated versions of the protein from these sources in the lab.

These approaches demonstrated that intelectin-2 specifically targets galactose, a simple sugar present in mucus and also coating some bacterial cells that are often linked to GI infections.

When intelectin-2 binds to certain microbes, it seems that these bacteria degrade over time. This may occur because the protein disrupts their outer membrane, although further research could clarify this.

Additionally, some bacteria that intelectin-2 successfully neutralizes have developed varying degrees of antibiotic resistance, adding significant value to these findings for future drug development.

For instance, bacteria like Staphylococcus aureus, known to cause sepsis, and Klebsiella pneumoniae, associated with pneumonia, fall into this category.

Kiessling continues, “Intelectin-2 first solidifies the mucus barrier, and then, if compromised, can manage the bacteria and limit their proliferation.”

Scientists estimate there are over 200 lectins encoded in the human genome, and research continues to uncover how they impact cell communication and immune functions.

Previously, researchers linked another protein, intelectin-1, to Crohn’s disease, suggesting these proteins have essential roles in preserving gut health.

The team also noted that in individuals with inflammatory bowel disease, levels of intelectin-2 are often unusually low or high. This might indicate issues with the mucus barrier not being adequately repaired or a loss of beneficial bacteria.

Looking ahead, both the defensive and offensive roles of intelectin-2 could be valuable. This could lead to the creation of drugs that either replicate the protein’s actions or enhance its effectiveness within the body.

Lectins are ancient proteins and likely existed long before the more sophisticated immune responses we rely on today. Yet, this study shows they can accurately target harmful bacteria rather than acting indiscriminately.

“Utilizing human lectins to combat antimicrobial resistance represents a groundbreaking strategy that leverages our own immune defenses,” Kiessling states. “Leveraging proteins that our body already employs for pathogen protection is a fascinating direction for future research.”

This research has been published in Nature Communications.