SEP 06, 2021 7:27 AM PDT

How a Genetic Mutation Could Lead to Leaky Gut

WRITTEN BY: Carmen Leitch

In our gut, there is a vast community of microorganisms. It's crucial that they remain there in the gastrointestinal tract, where they serve important functions. But if they or the molecules they generate escape from the gut, they can wreak havoc on the body. The intestinal epithelium is a layer of cells in the gut that functions as a permeable barrier that allows important molecules including nutrients and water to pass through, but keeps other stuff like bacterial proteins out. If that epithelial barrier loses its integrity, a condition called leaky gut, which has been linked to disorders like irritable bowel disease (IBD), may develop. IBD is thought to impact about 6 to 8 million people worldwide.

Declan McCole is a professor of biomedical sciences at UC Riverside. / Credit: Carrie Rosema.

Researchers have now identified genetic mutations that are associated with leaky gut. This study used a mouse model, human cells in culture, and tissue samples from IBD patients to show that when mutations that delete the function of a protein called PTPN2 occur, gut permeability increases. When a mutation disrupts PTPN2, the levels of another protein called claudin-2 increases. That seems to promote diarrhea by increasing the loss of sodium and water from the gut. The findings have been reported in the Journal of Clinical Investigation.

In mouse models, PTPN2 should reduce the expression of claudin-2. When a mutation takes PTPN2 out of commission, that brake comes off, leading to fluid loss in the gut. “In addition, PTPN2 also promotes an endogenous factor, called matriptase, that removes claudin-2 from the area of the cell membrane where it mediates its effects in allowing fluid loss to occur,” explained study leader Declan F. McCole, a professor of biomedical sciences in the University of California, Riverside School of Medicine.

The study suggested that therefore, PTPN2 can lead to the loss of fluid through two different mechanisms. When the mouse models were treated with synthetic matriptase, the defect could be reversed.

“Our work improves understanding of how the genetics of IBD can contribute to the altered physiology in patients that drives their symptoms,” said McCole, who added that the study seems to confirm previous research suggesting that JAK inhibitors might help restore a leaky gut.

A rare PTPN2 mutation has also been recently identified, and it leads to damage in the gut epithelium of children. This study indicated that the rare mutation increases leakiness in the gut epithelium too, but without causing the death of epithelial cells.

“This suggests that patients who develop this condition may exhibit ‘leaky gut’ before full-blown disease occurs,” McCole said.

Sources: University of California Riverside, Journal of Clinical Investigation

About the Author
BS
Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
SEP 18, 2022
Cell & Molecular Biology
A New Kind of Human Cell for Research
SEP 18, 2022
A New Kind of Human Cell for Research
It is extremely challenging to study human development. There are animal models that can tell us how general aspects of ...
SEP 28, 2022
Genetics & Genomics
Microprotein Mutations May Significantly Increase Alzheimer's Risk
SEP 28, 2022
Microprotein Mutations May Significantly Increase Alzheimer's Risk
The mitochondrion, commonly called the powerhouse of the cell, might be one of the best known organelles. This special o ...
OCT 02, 2022
Immunology
A Network Linking Aging, Inflammation, and Diet
OCT 02, 2022
A Network Linking Aging, Inflammation, and Diet
Our immune system is crucial to our health. It has to respond to pathogens and tissue damage quickly by initiating infla ...
OCT 28, 2022
Coronavirus
The New GenElute™-E Viral RNA/DNA Kit
OCT 28, 2022
The New GenElute™-E Viral RNA/DNA Kit
Three Advantages: Reduction in plastic use Time savings Better results Nucleic acids play an essential role in the funct ...
OCT 31, 2022
Genetics & Genomics
Ancient Viral DNA in Our Genome Has a Protective Function
OCT 31, 2022
Ancient Viral DNA in Our Genome Has a Protective Function
There is viral DNA in the human genome, and each instance traces back to an ancestor who was infected with a retrovirus. ...
DEC 01, 2022
Microbiology
Unusual Fungi - Ancient Creatures on Their Own Branch of Evolution
DEC 01, 2022
Unusual Fungi - Ancient Creatures on Their Own Branch of Evolution
This exotic new group of fungi includes these odd "earth tongue" organisms / (Photo: Alan Rockefeller, CC-BY-SA-4.0)
Loading Comments...