When parts of the small intestine become sick or die, doctors often have to cut them out. This surgery, called a radical small bowel resection, can save a life. But many patients later get serious liver problems, and up to 15% may need a liver transplant.
Researchers at Washington University School of Medicine tested a new compound in mice. The drug stays inside the gut, protects the liver, and helps the body take in nutrients after surgery.
Short Bowel Syndrome and Its Risks
Kids born early and babies with a severe gut disease called necrotizing enterocolitis often need this surgery. After the operation they may develop short bowel syndrome, where the shortened intestine cannot absorb food well.
Many of these children rely on long‑term IV feeding. While it keeps them alive, it also puts extra pressure on the liver, raising the chance of liver disease and the need for a transplant.
How Gut Bacteria and Good Cholesterol Matter
Dr. Brad Warner, a pediatric surgeon at WashU, found that chemicals made by gut bacteria can travel to the liver after surgery and cause damage. He also discovered that high‑density lipoprotein (HDL), known as “good” cholesterol, can block this damage.
A Drug That Works Only in the Gut
The team turned to liver‑X‑receptor (LXR) agonists, a class of medicines that raise HDL levels. Older LXR drugs affected the whole body and caused bad side effects. The new compound, named WUSTL0717, stays inside the intestines when taken by mouth.
Better Weight Gain and Nutrient Absorption
Three weeks after surgery, mice that received WUSTL0717 absorbed more nutrients and gained more weight than mice that did not get the drug.
Less Liver Scarring
The treated mice also showed less liver fibrosis – a buildup of scar tissue that harms liver function. Their livers had lower collagen levels and reduced activity of genes that create scar tissue.
"Our goal is to make medicines that work where they are needed without hurting the rest of the body," said researcher Elgendy.
Next Steps
WashU has filed a patent for using WUSTL0717 to treat short bowel syndrome. Future tests will see if the drug still helps when patients also receive IV nutrition, which can further stress the liver.