Researchers at Washington University School of Medicine in St. Louis have found toxin produced by the bacterium Escherichia coli (E. coli), lengthy identified to trigger diarrhea, additionally has different results on the human digestive tract.
The toxin, they discovered, adjustments gene expression within the cells that line the within of the intestine, inducing them to fabricate a protein that the bacterium then makes use of to connect to the intestinal wall.
The findings, revealed November 17 in Proceedings of the National Academy of Sciences, supply a clue to why recurrent however short-lived episodes of diarrhea may result in long-term dietary issues.
“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,” mentioned senior creator James M. Fleckenstein, MD, a professor of medication and of molecular microbiology.
“Decades ago, people worked out how the toxin causes diarrhea, 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 diarrhea,” added Fleckenstein.
Fleckenstein and first creator Alaullah Sheikh, PhD, a postdoctoral researcher, examine enterotoxigenic E. coli (ETEC), a toxin-producing pressure of E. coli that may be a frequent explanation for extreme, watery diarrhea.
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 — in different phrases, diarrhea.
Since oral rehydration remedy was invented within the 1970s, deaths from diarrhea have dropped by greater than 80 p.c worldwide. While invaluable at serving to folks survive a bout of diarrhea, the remedy does nothing to scale back the variety of circumstances.
Worldwide, younger youngsters nonetheless develop diarrhea a mean of thrice a yr, with the youngest and poorest youngsters bearing the brunt of the caseload — and of the long-term well being penalties.
Fleckenstein and Sheikh speculated that ETEC’s heat-labile toxin could be doing extra than simply inflicting acute diarrhea and dehydration. If so, it’d clarify the hyperlink between ETEC and malnutrition, stunting and different issues.
To discover different methods the toxin impacts the intestine, the researchers grew human intestinal cells in a dish and handled the cells with the toxin. They discovered that the toxin prompts a set of genes often known as CEACAMs. One specifically — CEACAM6 — codes for a protein that’s usually in cells of the small gut at low ranges.
Further experiments revealed that the toxin causes cells to provide extra CEACAM6 protein, which the micro organism then makes use of to connect to intestinal cells and ship much more toxin. Moreover, utilizing intestinal biopsy specimens from folks in Bangladesh contaminated with ETEC, the researchers confirmed that CEACAM6 expression will increase within the small gut throughout pure an 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,” Sheikh mentioned.
“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 persevering with to check the hyperlink between ETEC and malnutrition, stunting and different well being penalties.
“We are trying in the lab to understand the role of ETEC and its toxins as they relate to nondiarrheal effects of ETEC infection, particularly in young children in developing countries,” Fleckenstein mentioned.
“There’s a lot of work to be done to explore how the toxins might be related to these long-term consequences of diarrhea,” added Fleckenstein.
(This story has been revealed from a wire company feed with out modifications to the textual content.)