Psoriasis-linked gene mutation may also play a surprising role in gut health

A mutation previously linked to skin disorders like psoriasis may also play a surprising role in gut health, according to new research published by scientists at VIB-UGent and colleagues from UGent, the University of Barcelona, and University College London. This mutation activates skin immune responses but also affects the intestine. This finding, published in EMBO Molecular Medicine, reveals a new connection between genetics, the immune system, and the gut, which may have therapeutical implications. 

Scientists under the leadership of Dr. Inna Afonina and Prof. Rudi Beyaert (VIB-UGent Center for Inflammation Research) have found that a mutation in the gene CARD14, known for activating skin immune responses in psoriasis patients, also affects the intestine. This mutation reduces gut motility, promotes mild inflammation, and increases vulnerability to bacterial infections. 

Using a mouse model that expresses the human psoriasis-associated CARD14 mutation in intestinal epithelial cells (IECs), the researchers found that the mice developed slower intestinal transit despite no damage to the gut lining or enteric nervous system. Such changes in intestinal motility are associated with many diseases. 

Our study reveals that CARD14's impact isn't limited to the skin. In the intestine, this mutation leads to subtle but important changes that may contribute to subclinical intestinal symptoms in patients who carry it." 

Aigerim Aidarova, lead author of the study, VIB-UGent

Gut-immune crosstalk 

Further analysis showed that the mutation altered the gene expression profile of IECs, including a drop in antimicrobial peptides produced by Paneth cells – specialized cells critical for gut immunity. Together with changes in the gut microbiome, this decreased antimicrobial production was linked to reduced microbial diversity and a heightened susceptibility to intestinal bacterial infections. 

These findings offer new insight into the crosstalk between genetic immune regulators and gut function, and suggest that psoriasis patients with CARD14 mutations may face previously unrecognized issues that could set the stage for the development of intestinal disease. 

"This research broadens our understanding of how a single genetic variant can influence different organs in the body," said Prof. Rudi Beyaert. 

"It also provides a valuable animal model to further study gut inflammation and motility disorders," adds Dr. Inna Afonina. 

The study opens new avenues for investigating the connection between genetics, immune signaling, and gastrointestinal health, with potential therapeutic implications. It also suggests that raising awareness of intestinal disease symptoms among psoriasis patients and dermatologists could be beneficial.