Toxin provides clues to long-term effects of diarrhea caused by E. coli

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CHICAGO, Dec. 9 (Xinhua) -- Researchers at Washington University School of Medicine in St. Louis have discovered that a toxin produced by the bacterium Escherichia coli, or E. coli long known to cause diarrhea, also has other effects on the human digestive tract.

To find other ways the toxin affects the gut, the researchers grew human intestinal cells in a dish and treated the cells with the toxin. They found that the toxin activates a set of genes known as CEACAMs. One in particular, CEACAM6, codes for a protein that is normally in cells of the small intestine at low levels.

Further experiments revealed that the toxin causes cells to produce more CEACAM6 protein, which the bacteria then uses to attach to intestinal cells and deliver even more toxin.

Moreover, using intestinal biopsy specimens from people in Bangladesh infected with enterotoxigenic E. coli (ETEC), a toxin-producing strain of E. coli that is a common cause of severe, watery diarrhea, the researchers showed that CEACAM6 expression increases in the small intestine during natural infection.

"CEACAM6 is expressed in what is called the brush border of the small intestine, which is where all your vitamins and nutrients get absorbed," said first author Alaullah Sheikh, a postdoctoral researcher. "This is one of the first pieces of evidence that ETEC can change the intestinal surface. We don't yet know how long that lasts and what that means for people who are infected, but it stands to reason that damage to this part of the body could affect the ability to absorb nutrients."

The researchers are continuing to study the link between ETEC and malnutrition, stunting and other health consequences.

"We are trying in the lab to understand the role of ETEC and its toxins as they relate to non-diarrheal effects of ETEC infection, particularly in young children in developing countries," said senior author James M. Fleckenstein, a professor of medicine and of molecular microbiology. "There's a lot of work to be done to explore how the toxins might be related to these long-term consequences of diarrhea."

Worldwide, young children develop diarrhea an average of three times a year, with the youngest and poorest children bearing the brunt of the caseload and of the long-term health consequences.

The findings, posted on the university's website on Wednesday, have been published in Proceedings of the National Academy of Sciences. Enditem

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