Researchers from Johns Hopkins Children's Center say they have identified a gene pathway involving the mineral zinc in mice that may someday point the way to using zinc-based supplements to directly help people with a rare disorder called short bowel syndrome (SBS), reports ScienceDaily.

The findings, published in Nature Communications, help advance efforts toward more effective, potential treatment regimens for both children and adults with the debilitating condition.

SBS, which affects 10,000-20,000 adults and children in the United States, is marked by damage to and shortening of the small intestine. While in rare cases, children can be born with SBS, it is more often a complication of conditions such as necrotizing enterocolitis—a disease that affects the intestines of premature infants.

Children with SBS have a reduced ability to absorb nutrients from the diet, often require intravenous nutritional support, and experience significant complications including malnutrition, dehydration, unintentional weight loss and death. Treatment and management approaches—including special diets, surgical procedures and, occasionally, small bowel transplants, are only partially effective, and often result in side effects including infection and extended hospital stays.

"Short bowel syndrome is a huge problem, and has a great impact on patients who experience this condition and their families," says David Hackam, surgeon-in-chief and co-director of Johns Hopkins Children's Center and senior author of the study. Their study was designed, he said, to identify whether there may be new treatment options for patients with this disease. Surprisingly, they identified a previously unrecognized role for zinc, to protect and even grow what bowel remains in people with SBS.

The researchers used a mouse model to simulate SBS and observed the natural adaptation of the intestines, where the small hair-like structures became longer in an attempt to improve the absorption of nutrients.

That natural adaptation alone, however, was not enough for complete recovery. The team identified the specific gene pathways responsible for this adaptation and used human stem cells in mice to reproduce the condition of the human gut. Using single-cell RNA sequencing, they found that certain genes, specifically SLC39A4 and SLC39A5, which help transport zinc in the body, were significantly more active in mice with SBS. This allowed us to propose a theory that the addition of zinc can contribute to the treatment of the disease.

A high-zinc diet led to improved survival rates, weight maintenance and improved bowel function in mice compared to a control group.

The researchers examined also human tissue samples and confirmed elevated levels of zinc transporter genes in patients with SBS.

Their research findings suggest that zinc supplementation may be used as a therapeutic strategy, although further studies are needed to determine the safety and efficacy of this treatment method.

Hackam and his colleagues emphasize that additional experiments, including clinical ones, are needed to confirm the role of zinc in the treatment of SBS in humans. But if successful, zinc supplementation could considerably improve the quality of life of thousands of people suffering from this disorder.