Researchers have conducted a study to find out if diarrhea serves a purpose.
They wondered if diarrhea is a symptom of disease, or if it actually helps clear the bacteria causing an infection.
They found that, in sick mice, proteins caused microscopic leaks in the intestinal wall that let water in, making the mouse poop looser and limiting disease severity.
Diarrhea can have many different causes, including infections, certain types of medications, too much caffeine or alcohol and many more.
It happens when there’s an excess of water in the intestines, which is normally re-absorbed by the body.
The intestinal wall is lined with cells, and some water can pass through the cells, holes in the lining or via junctions between the cells.
“The hypothesis that diarrhea clears intestinal pathogens has been debated for centuries,” said corresponding author of the study, Dr Jerrold Turner of the BWH Departments of Pathology and Medicine.
“Its impact on the progression of intestinal infections remains poorly understood.
“We sought to define the role of diarrhea and to see if preventing it might actually delay pathogen clearance and prolong disease.”
To conduct the study, the researchers used a mouse infected with a bacteria called Citrobacter rodentium – the mouse equivalent of an E.coli infection.
Within two days of the mouse being infected, the researchers saw an increase in the permeability of the mouse’s intestinal barrier – leading to water entering the intestines, causing diarrhea.
This occurred well before inflammation cellular damage of the intestines.
The researchers discovered two new proteins involved in causing diarrhea – interleukin-22 and claudin-2, which humans possess too.
They found that when the mouse was infected, immune cells travelled to the intestinal wall and produced interleukin-22.
Interleukin-22 binds to cells on the intestinal wall, causing the release of another protein called claudin-2.
It’s claudin-2 that causes the leak in cellular junction in the intestinal wall, allowing water to enter it and cause diarrhea.
The researchers tested three different kinds of mice – regular mice, genetically modified mice that produce large amount of claudin-2, and mice that didn’t make any claudin-2.
The regular mice had diarrhea when they got sick, and the mice that made more claudin-2 always had diarrhea.
The mice that didn’t make any claudin-2 had more sever injuries to their intestinal lining, and they still had diarrhea, because it seemed their immune system, though attacked the cells, help make some diarrhea.
Overall, the diarrhea induced by these two signalling molecules helped promote pathogen clearance and limited disease severity.
While some researchers have proposed limiting claudin-2 to prevent diarrhea, Dr Turner and his colleagues say that this signalling pathway may be critical for combating certain infections, especially in the early stages of a disease.
It’s still not clear if this mechanism is important in fighting all infections and if it’s also important in humans, but since humans also have these proteins, the mouse model could serve as a useful preliminary study to human studies.
