Why Do Sick Bodies Turn Poop Into Diarrhoea?

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Despite thousands of years of pant-crapping history, there's a surprising amount we don't know about diarrhoea. There's a couple of ways we've figured out how to treat the symptom. But a lot of scientists' understanding of diarrhoea -- from illnesses such as traveller's diarrhoea -- is more based on intuition than data.

An international team of researchers is trying figure out how and why the body lets all that extra water get into your poop. Or rather, in certain cases where bacteria causes diarrhoea in mice -- call it traveller's diarrhoea for mice -- since that's the way they did their research. But the study could have all sorts of implications for the way we understand and treat the symptom. Also, it's just cool as hell to better understand why your body gets sick and smelly.

"So we set out to test that in a more detailed way," principle investigator Jerrold Turner from Brigham and Women's Hospital and Harvard Medical Center told Gizmodo. "We asked, 'How does the water get across the lining in your intestine?'"

Again, all this work was in mice, not humans. But humans have all these proteins in their body as well, so it could at least serve as a useful model to study the symptom. Anyway, here goes.

The intestinal wall is lined with cells much like the skin is, and some, but not a lot of water, can get through. Water can pass through the cells themselves, it can pass through holes in the lining, or it can pass through the junctions that normally seal the space between the cells.

When the mouse bodies got sick, immune cells came to the intestinal wall and released a protein called interleukin-22 (we have these proteins, too). This protein bounded to the cells on the intestinal wall, and told them to release another protein, called claudin-2. This protein caused a leak in the cell junctions that let water in, making the mouse poo runnier.

The researchers performed all types of tests on three kinds of mice to make their conclusion: Regular control mice, mice that made lots of claudin-2, and mice that didn't make any (the latter two were genetically modified to be that way). The regular mice had runnier poop when they got sick, and the mice who made lots of claudin-2 sort of always had runny poop.

But the mice without the caudin-2 had it worst of all. "Their immune system went crazy trying to clear this infection it couldn't," said Turner. These mice had more severe injury to their lining cells -- and they still ended up having diarrhoea, because it looked like the immune system attacked the cells to help make some bacteria-clearing diarrhoea. The researchers published their results in the journal Cell Host and Microbe today.

Again, "clinical trials in mice don't often lead to success in people," said Turner. But simply understanding how diarrhoea happens in response to a bacterial infection is important information. There's still doubt as to whether diarrhoea's actual purpose is to flush the body of pathogens, for example. This study adds evidence to that.

I sent the study to Michael Helmrath, a surgeon who works on intestines and has grown intestines in his lab. "Nice paper," he said in an email. "A very good job." But he did point out some caveats. "They KEY point here is the mechanism for interleukin-22 and the innate response to prevent infectious diarrhoea. It is not clear if this is the mechanism for all infections, but the concept is novel and interesting." Obviously this is just one study on one mechanism in our complex bodies.

But the study has implications beyond just understanding runny poop. Some scientists have considered looking into claudin-2 and its role in irritable bowel disease, for example. But if the body really is using these chemicals to get rid of infections, things might end up even worse -- no one wants to be the mouse with the wrecked immune system.

"Diarrhoea is a major cause of illness and death worldwide," said Turner. "People are working on drugs to prevent diarrhoea. But this tells us that... you have to be careful about it. In the case of this pathogen, if you block it, you make the infection much worse."

Anyway, diarrhoea is an enigma. But next time you're screaming from the toilet seat, just think that your body is probably doing this for a good reason.

[Cell Host and Microbe]


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