Intestinal mucus and goblet cell function

The gut’s first line of defense is a mucus barrier

The intestine is continuously exposed to complex challenges from food, digestive products, and the vast community of microorganisms that constitutes the gut microbiota. These microorganisms are essential for human physiology and health, yet they must be kept at a safe distance from our tissues to maintain intestinal homeostasis. A central component of this defense is the intestinal mucus barrier, a specialized mucus layer composed primarily of mucins and produced and secreted by goblet cells in the intestinal epithelium.

Our research has contributed to the discovery that the mucus layer forms an effective physical barrier that limits direct contact between bacteria and the intestinal epithelium. These findings have changed our understanding of how host–microbiota interactions are controlled at the mucosal surface. More recently, our studies have revealed that goblet cells are not a homogeneous cell type but comprise multiple specialized populations with distinct roles in mucus production and secretion.

When the mucus barrier fails, disease can develop

Alterations in mucus barrier properties and goblet cell function are associated with several intestinal diseases, including inflammatory bowel disease and colorectal cancer. We have shown that the mucus layer becomes permeable to bacteria before histologically detectable inflammation develops in experimental models of UC. These findings suggest that impaired mucus barrier function is not merely a consequence of established inflammation but may represent an early and potentially disease-driving mechanism.

Our ongoing studies also investigate mucus barrier properties and goblet cell function in EED, a condition associated with chronic intestinal dysfunction and malnutrition, as well as CAC. By studying these distinct disease settings, we aim to identify both shared and disease-specific alterations in the intestinal barrier system.

Understanding the early mechanisms of disease

A major goal of our research is to understand how distinct goblet cell populations produce, secrete, and organize mucus to establish a functional barrier, and how these processes are altered during disease. Despite the fundamental importance of the mucus barrier, surprisingly little is known about the mechanisms that control mucus secretion and how newly secreted mucus is organized into a functional barrier.

To address these questions, we combine high-resolution, high-speed microscopy with molecular and biochemical approaches across complementary experimental model systems. We investigate both the secretory processes of goblet cells and the functions of key molecular components of the mucus layer, including MUC2, FCGBP, and CLCA1. This allows us to link molecular mechanisms to mucus structure and barrier function and to determine how these relationships change during disease development.

An important goal is to identify disease-associated alterations that can be developed into biomarkers of disease activity, prognosis, and treatment response. Ultimately, we aim to translate a deeper mechanistic understanding of the mucus barrier into improved diagnostics and new therapeutic strategies targeting the barrier itself, its molecular components, and the cells that build and regulate it.

The research group is part of the Mucin Biology Groups.
For more information visit our external website: The Sahlgrenska Academy Mucin Biology Groups.