Washington [US], December 13 (ANI): A study published in proceedings of the National Academy of Sciences reveals that the toxin produced by the Escherichia coli (E. coli) bacterium which causes diarrhoea could lead to long-term nutritional problems.
Researchers at Washington University School of Medicine in St. Louis have discovered that a toxin which leads to recurrent of short-term diarrhoea episodes could have other effects on the human digestive tract as it changes gene expression in the cells that line the inside of the gut, inducing them to manufacture a protein that the bacterium then uses to attach to the intestinal wall.
Senior author James M. Fleckenstein, MD, a professor of medicine and of molecular microbiology said, "There's more than meets the eye with this toxin. It is basically changing the surface of the intestine to benefit itself, probably ultimately to the detriment of the host,"
According to Fleckenstein, decades ago, people worked out how the toxin causes diarrhoea, but until recently, nobody really had the tools to delve into what else this toxin might be doing.
We're trying to put together the pieces of the puzzle to find out how toxin-producing E. coli might be driving malnutrition and other ripple effects of diarrhoea," added Fleckenstein.
Fleckenstein and first author Alaullah Sheikh, PhD, a postdoctoral researcher, study enterotoxigenic E. coli (ETEC), a toxin-producing strain of E. coli that is a common cause of severe, watery diarrhoea.
The bacterium's so-called heat-labile toxin causes ion channels on intestinal cells to open, triggering an outpouring of water and electrolytes into the digestive tract that is called diarrhoea.
Worldwide, young children still develop diarrhoea 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, says study.
Fleckenstein and Sheikh speculated that ETEC's heat-labile toxin might be doing more than just causing acute diarrhoea and dehydration. If so, it might explain the link between ETEC and malnutrition, stunting and other problems.
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 ETEC, the researchers showed that CEACAM6 expression increases in the small intestine during natural infection.
"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," added Sheikh.
Fleckenstein, Sheikh and colleagues 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," Fleckenstein said. (ANI)