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New drug protects liver after intestinal surgery and boosts nutrient absorption

A new gut-focused drug could help prevent liver failure after life-saving intestinal surgery.

Date:

March 18, 2026

Source:

WashU Medicine

Summary:

A risky but often lifesaving surgery that removes damaged parts of the small intestine can leave patients facing a new threat: serious liver damage with no available treatment. Now, scientists have developed a promising compound that works directly in the gut to shield the liver and improve how the body absorbs nutrients. In mouse studies, the drug boosted weight gain, reduced harmful liver scarring, and avoided side effects by staying confined to the intestines.

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FULL STORY

Scientists have created a gut-targeted drug that protects the liver after major intestinal surgery. In early tests, it improved nutrient absorption and reduced liver damage—offering hope where no treatments currently exist. Credit: Shutterstock

When sections of the small intestine become diseased or die, surgeons often must remove the damaged tissue. This procedure, known as a radical small bowel resection, can save lives. However, it comes with a major downside. Many patients later develop serious liver problems, including long-term damage or even liver failure that may require a transplant. Currently, no medications exist to prevent or treat this complication, which affects up to 15% of patients after surgery.

Researchers at Washington University School of Medicine in St. Louis have developed a new compound and tested it in mice. Their findings suggest the drug may protect the liver while also improving the body's ability to absorb nutrients after surgery. Importantly, the compound works only within the gastrointestinal tract, which may help avoid unwanted side effects elsewhere in the body.

The study is published March 6 in Gastroenterology.

"Our goal is to advance a therapeutic drug capable of preserving liver function and mitigating the necessity for liver transplants in people who've undergone small bowel surgery," said Gwendalyn Randolph, PhD, the study's senior author and the Emil R. Unanue Distinguished Professor of Immunology in the WashU Medicine Department of Pathology & Immunology. "This study offers a promising pathway for developing such a treatment."

Short Bowel Syndrome and Long-Term Risks

Patients who undergo small bowel resection include premature infants with necrotizing enterocolitis, a severe intestinal disease that requires removal of damaged tissue. After surgery, many develop short bowel syndrome, a condition in which the shortened intestine struggles to absorb nutrients effectively.

Children with this condition often depend on long-term intravenous feeding through a pump. While necessary, this approach can further strain the liver. As a result, these patients face a high risk of liver disease and may eventually need a transplant.

Gut Bacteria, "Good" Cholesterol, and Liver Protection

The late Brad Warner, MD, a pediatric surgeon and researcher at WashU Medicine, focused much of his work on improving outcomes for children with short bowel syndrome. In a 2021 study conducted with Randolph, researchers discovered that substances produced by gut bacteria can travel to the liver after surgery and cause damage.

They also found that high-density lipoprotein, or HDL, often called "good" cholesterol, can help protect the liver by blocking these harmful substances.

Targeting the Gut Without Whole-Body Side Effects

Building on these findings, the research team turned to a class of drugs known as liver X receptor agonists, which increase HDL production in the liver and intestines. Earlier versions of these drugs affected the entire body and caused serious side effects.

To address this issue, the scientists tested a "gut-restricted" version designed to act only in the intestines. The compound, originally identified by a pharmaceutical company but never brought to market, was synthesized for this study by Bahaa Elgendy, PhD, an associate professor of anesthesiology at WashU Medicine and a co-author with expertise in medicinal chemistry.

When given orally to mice, the compound, called WUSTL0717, remained in the intestines rather than spreading throughout the body.

Improved Nutrient Absorption and Reduced Weight Loss

The researchers evaluated whether WUSTL0717 could counteract the severe weight loss that often follows small bowel resection. Mice treated with the drug three weeks after surgery showed improved nutrient absorption and gained more weight compared to untreated mice.

Reduced Liver Scarring and Healthier Liver Function

The team also found that the compound protected the liver from fibrosis, a buildup of scar tissue that interferes with normal function. Treated mice had lower levels of collagen, a major component of scar tissue, than untreated mice or those that underwent a