A team of scientists in the United States has made a hopeful discovery that could alter the lives of thousands of preterm babies who are given life-saving intestinal surgery but subsequently develop serious liver disease. Researchers at Washington University School of Medicine in St Louis have created a novel investigational medication that may preserve the liver and enhance nutrition in patients who have had significant amounts of their small intestine surgically removed. 

The findings, published on March 6 in the journal Gastroenterology, are based on laboratory studies in mice and suggest that the molecule may one day help prevent liver failure in individuals with short bowel syndrome, a dangerous illness that frequently occurs after major intestinal surgery. 

When intestines get sick or die, doctors undertake drastic small bowel resections. The treatment is frequently performed on premature neonates suffering from necrotising enterocolitis, a life-threatening infection that destroys parts of the intestines. Although removing the diseased intestine can save the infant's life, the surgery shortens the digestive tube significantly. 

Simply put, the body struggles to absorb enough food and nutrients. Even if patients eat normally, their shorter intestines cannot process the food adequately. Many youngsters rely on long-term intravenous feeding, which delivers nutrition directly into the bloodstream via a vein. 

However, this treatment has a high cost. According to studies, up to 15% of people who undergo small intestinal resection develop severe liver damage. Over time, the liver scars (a process known as 'fibrosis'), which can lead to liver failure and the need for a transplant. 

"Our goal is to advance a therapeutic drug capable of preserving liver function and reducing the need for liver transplants in people who have undergone small bowel surgery," said Gwendalyn Randolph, PhD, the study's principal author and professor of immunology at Washington University. "This study offers a promising pathway for developing such a treatment." 

Previous research by the same team discovered that following intestinal resection, toxic chemicals produced by gut bacteria can move directly to the liver and cause damage. Researchers also discovered that HDL, popularly known as "good cholesterol," can operate as a protective shield, inhibiting these dangerous chemicals. 

Building on that knowledge, the researchers concentrated on drugs that activate a biological switch known as the liver X receptor, allowing the body to manufacture more HDL. Earlier versions of such medications had a wide-ranging effect and were associated with severe adverse effects, such as liver damage and increased risk of cardiovascular events. 

To address this issue, the scientists developed a "gut-restricted" molecule, which means the medicine remains in the digestive tract rather than circulating throughout the body. Bahaa Elgendy, PhD, a medicinal chemist, synthesised the new chemical, WUSTL0717, for the study. 

When administered orally to mice who had undergone intestinal surgery, the medication stayed primarily within the intestines. The treated mice had better nutrient absorption and regained weight faster than untreated mice. 

Most notably, their livers had significantly less scarring. Scientists discovered lower levels of collagen, a major component of scar tissue, as well as reduced activity of fibrosis-related genes. 

"Our future goal is to create the next generation of tissue-specific therapies that preserve therapeutic benefit while reducing unintended systemic effects," he stated. 

Experts believe the study is especially important for children with short bowel syndrome, who face ongoing medical issues. 

"The absence of therapies for patients with short bowel syndrome has profound implications for their long-term health," stated Colin A. Martin, MD, a paediatric surgeon and research co-author. "These preclinical findings represent a crucial leap forward in our goal of developing a treatment that safeguards liver function and improves nutrient absorption." 

The researchers have already filed a patent for the molecule and intend to do additional tests to see how the medicine works alongside long-term IV (intravenous) feeding, which can stress the liver. 

Although the treatment is still in the early stages of development, scientists believe it opens the door to protecting the liver by targeting the gut, providing new hope for vulnerable premature babies who survive life-saving surgery only to face another life-threatening illness later in childhood.