Inflammatory bowel disease (IBD) is a term used to describe two chronic conditions, Crohn’s disease and ulcerative colitis, that result in inflammation within the intestines.
This autoimmune disorder affects approximately 3 million adults in the US and occurs when the immune system attacks healthy tissues, leading to symptoms such as diarrhea, rectal bleeding, fatigue, weight loss, and stomach cramps.
The layer of cells that lines the intestine, known as the intestinal epithelium, serves a crucial function in IBD since it is highly susceptible to disruption during episodes of gut inflammation.
One type of epithelial cell, the Paneth cells, are specialized and produce antimicrobial peptides to manage the gut microbiota – the complex community of microorganisms residing within the gut.
In a mouse study conducted by biomedical scientist and IBD specialist Declan F. McCole at the University of California, a research team discovered that diminished activity of the PTPN2 gene – a gene linked to IBD risk – within the intestinal epithelial cells resulted in decreased production of Paneth cell antimicrobial peptides.
Published in the journal Cellular and Molecular Gastroenterology and Hepatology, the study provides important evidence of the critical relationship between PTPN2 and Paneth cells, which are key in sustaining the typical characteristics of the gut microbiome.
“Loss of PTPN2 can lead also to selective loss of Paneth cells in the intestinal epithelium,” according to Declan F. McCole, a professor of biomedical sciences in the School of Medicine.
“This loss of PTPN2 causes significant changes in the gut microbiota and increases a particular E. coli.”
Escherichia coli, also known as E. coli, are a type of bacteria that can be found in various environments, including the intestines of animals and humans, as well as certain foods.
According to McCole’s explanation, a particular type of E. coli, known as adherent-invasive E. coli (AIEC), has been observed to increase in individuals with inflammatory bowel disease (IBD) and exacerbate inflammation. Initially detected in patients with Crohn’s disease, AIEC has the capability to attach to and invade both epithelial cells and immune cells, such as macrophages.
“AIECs are the strongest candidate for a causal role for bacteria in IBD,” he added.
McCole explained that a significant number of individuals living with inflammatory bowel disease (IBD) experience dysfunction in their Paneth cells, which can serve as an indication of the disease.
The production of antimicrobial peptides by these cells plays a crucial role in maintaining the intestinal barrier’s protective function by regulating the interactions and relative proportions of various bacteria. Moreover, these peptides are involved in improving the functioning of neighboring intestinal stem cells.
“We know that in IBD, Paneth cells are often unable to produce sufficient antimicrobial peptides or respond appropriately to gut bacteria,” McCole added.
Changes in the structure of Paneth cells can be associated with functional defects that limit their capacity to secrete protective antimicrobial peptides, resulting in an increase in the populations of bacteria associated with inflammatory bowel disease (IBD), including AIEC. These alterations in the physical appearance of Paneth cells can also serve as an indication of disease in IBD, particularly Crohn’s disease.
The research was backed by various institutions, including the Crohn’s and Colitis Foundation, Swiss National Science Foundation, American Gastroenterological Association, Science Without Borders Program, and California Institute of Regenerative Medicine.
This study “sets the foundation for our new research project that will identify pharmacologic agents capable of rescuing Paneth cell function and reducing the contributions of microbes to intestinal inflammation,” McCole remarked.
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