The intestines of the African clawed frog develop cleanly and anticlockwise, precisely like those of humans. Trials now demonstrate how that procedure can go wrong. Know more about the correlation between misregulated metabolism and the intestine.
Researchers from North Carolina State University in Raleigh reported on February 19 in Development that altering a tadpole’s metabolism sets off a series of cellular changes that misdirect the growth of its intestines. Their research sheds new light on the possible causes of intestinal malrotation, a similar congenital defect seen in people.
Mehul Raval, a paediatric surgeon at Ann & Robert H. Lurie Children’s Hospital of Chicago who was not involved in this study, says, “Anything that illuminates how we could protect the embryo and the foetus early in development and prevent any type of congenital abnormalities, is fascinating, and it’s exciting.”
According to the study’s authors, up to 1 in 500 human babies have intestinal malrotation. However, malrotation can go unnoticed for a long period, thus Raval speculates that there may be an even higher number of cases. It is typically discovered when the stomach becomes so twisted that blood flow is blocked or blockages result.
According to N.C. State developmental biologist Nanette Nascone-Yoder, “think of the intestine as a garden hose.” “To prevent kinks and knots, you must wind it up with extreme caution.”
Paediatric surgeon Janice Taylor of the University of Florida in Gainesville, who was not involved in the study, notes that malrotation can occur in conjunction with other defects, but she is unsure of the cause.
Because frogs’ intestines are lengthy and looping, just like human intestines, Nascone-Yoder and colleagues resorted to frog embryos. Furthermore, because the embryos are transparent and develop outside of their mothers’ bodies, it is simple to track their growth.
The intestine normally winds anticlockwise as it matures in both humans and frogs. This occurs in the early stages of a tadpole’s growth, ideally on day three or four. Before and throughout this developmental stage, the researchers treated Xenopus laevis embryos to atrazine, a popular herbicide and recognised hormone disruptor in humans (SN: 1/21/15). The intestines of many of the frogs were discovered to be coiled incorrectly—clockwise.
After doing additional experiments, the scientists discovered that atrazine interfered with the tadpoles’ metabolism, which had the cascading effect of preventing the full conversion of glucose to energy. According to Nascone-Yoder, “We can assume that [this reaction] inhibits the ability of cells to arrange in the growing intestine.” The frogs’ intestines were not only coiled clockwise but also too malformed to occupy the space that they normally would have filled.
This does not imply that atrazine causes malrotation of the intestine in humans. The atrazine levels that the researchers utilised were really 1,000 times higher than what is typically found in the environment. However, it does imply that a role for metabolic disturbance might exist. “The lengthening of the GI tract in humans may also be slightly influenced by an environmental [effect] or a genetic defect, such as an inborn error of metabolism,” adds Nascone-Yoder.
Tadpoles exposed to the herbicide also had higher concentrations of harmful chemicals known as free radicals, according to the researchers. These free radicals can damage intestinal growth-promoting mechanisms when present in excess. Antioxidants, on the other hand, can fight them off, which is why more than half of the tadpoles that had an antioxidant treatment before being exposed to the herbicide developed normal, healthy intestines.
This work is a step in the right direction, even though it doesn’t explain what causes intestinal malrotation in human foetuses or whether antioxidants can stop it. “The key takeaway is that our research provides fresh perspectives on intestinal malrotation, as there wasn’t much explanation available before,” adds Nascone-Yoder.
