A study has found that E. coli creates a toxic chemical that changes intestinal cells to provide self-benefit, an ability that researchers say could provide a clue to why the bacteria have been linked to nutritional problems such as malnutrition and stunted growth. Escherichia coli is known to cause diarrhea, and scientists at Washington University School of Medicine in St. Louis have discovered that a toxin produced by the bacterium has other effects on the human digestive tract. The toxin, they found, changes gene expression in the gut’s epithelial cells, 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, explained that the E. coli-produced toxin ” is basically changing the surface of the intestine to benefit itself, probably ultimately to the detriment of the host. 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.”
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 diarrhea. The bacterium’s toxin causes ion channels on intestinal cells to open, allowing a flow of water and electrolytes into the digestive tract, ie, diarrhea.
They speculated that this toxin might be doing more than just causing acute diarrhea and dehydration. If so, it might explain the link between ETEC and malnutrition, stunting and other problems.
After growing human intestinal cells in a dish and inoculating them with the toxin, the researchers found that it activates a gene CEACAM6, which codes for a protein normally in cells of the small intestine at low levels; the toxin causes cells to produce more CEACAM6 protein, which the E. coli then uses to attach to intestinal cells and deliver even more toxin.
“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 said. “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.”
Fleckenstein, Sheikh and colleagues are continuing to study the link between ETEC and malnutrition, stunting and other health consequences.
Reference:
Sheikh A, et al. “CEACAMs serve as toxin-stimulated receptors for enterotoxigenic Escherichia coli.” Proceedings of the National Academy of Sciences, 2020; 117 (46): 29055 DOI: 10.1073/pnas.2012480117.
