A remarkable new study by undergraduates at the University of Virginia may help explain recurrences of Crohn’s disease in children and may open the door to new ways to treat or cure this devastating disease.
Crohn’s disease is an inflammation of the digestive tract that can be debilitating and potentially life-threatening. Symptoms include abdominal pain, weakness, fatigue, and malnutrition, which occur because the body is unable to absorb nutrients. Although Crohn’s disease is most common in adults, it affects tens of thousands of children in the United States alone. Many of these children struggle to attend school, causing major disruptions to their lives and childhoods. These children may suffer from stunted growth and delayed puberty, and may need to have parts of their intestines surgically removed.
New UVA research suggests why children with relapsing Crohn’s disease may experience repeated relapses even after they appear to have recovered. Working with Dr. Chelsea Murray at the UVA School of Medicine, undergraduate student Rebecca Pierce found that children with relapsing Crohn’s disease continue to experience disruption of their microbiome — the collection of microorganisms that live in the gut — even after treatment has successfully suppressed inflammation.
The relationship between gut microbiota dysbiosis and inflammation in Crohn’s disease has been a long-standing question. Leveraging a pediatric cohort study from the University of Virginia, Rebecca has shown that gut microbiota dysbiosis exists even when intestinal inflammation is suppressed. Our study suggests that persistent microbial imbalance may be an important factor in the course of the disease in children.”
Chelsea Murray, University of Virginia School of Medicine and Department of Infectious Diseases and Global Health
This insight could be key to helping doctors develop ways to better treat or even cure Crohn’s disease, said Dr. Ningjiun Jang, a senior scientist in Murray’s lab who also mentored Pierce. “Currently, most treatments for Crohn’s disease are focused on managing symptoms, which usually means taking a variety of medications to address inflammation and promote healing,” Dr. Jang said. “But these are not cures, meaning patients need to continue taking these medications to prevent relapses. In our study, we found that although symptoms were alleviated, the bacterial composition in the gut did not return to normal, which may be why these patients relapse.”
Crohn’s disease in children
Because Crohn’s disease is most common in adults, most research has focused on adult patients, but the new UVA findings shed important light on Crohn’s disease in children.
The researchers hypothesized that children with recurrent Crohn’s disease have persistent inflammation along with changes in the composition of bacteria and other microbes in their gut. As scientists increasingly recognize the importance of these microbes in maintaining health, disruptions to the microbiome are thought to be a major cause of disease.
Pierce, now a medical student at Georgetown University, and his colleagues compared biopsy samples taken from the intestines of children with Crohn’s disease in remission with samples from a control group of children with no signs of Crohn’s disease. The researchers found a big difference: The children with Crohn’s disease showed a significant reduction in bacteria, including: Streptococcus others, Oribaterium. (Oribaterium It has been linked to gut microbiota disruption. Additionally, the researchers observed significant changes in immune cells, including increased numbers of CD4+ T cells, which play a key role in inflammation.
Perhaps counterintuitively, children with Crohn’s disease also had a stronger barrier of epithelial cells lining the intestine, suggesting that existing treatments for Crohn’s disease, while effective, don’t fully address the underlying problems that cause the disease, the researchers say.
“We found persistent microbial imbalances and subtle inflammatory changes even in a cohort of pediatric Crohn’s disease patients in remission,” Pierce said. “Current treatments focus on treating the clinical symptoms that may predispose patients to relapse. Our study suggests that incorporating therapies that target the underlying causes of gut dysbiosis may reduce relapses and improve treatment.”
The researchers note that that could lead to new and better treatments for both children and adults with Crohn’s disease. For example, doctors might try to restore balance to the microbiome by using fecal transplants or administering a customized cocktail of healthy microbes to replace those lost.
“Our study suggests that restoring the bacterial composition to normal may prevent relapse and cure Crohn’s disease in these patients,” Jiang said.
Murray noted that this new discovery was made possible by the University of Virginia’s culture of collaboration.
“Clinical research is key to improving children’s health,” Murray said. “Rebecca’s work has brought together experts in infectious diseases, pediatric gastroenterology and bioinformatics to address diseases in pediatric patients at the University of Virginia, and we are pleased to continue this collaborative model.”
Understanding the microbiome to prevent, treat and cure disease is a priority for the University of Virginia’s Trans-University Microbiome Initiative (TUMI), which brings together researchers from across the university to advance this cutting-edge field of biomedical research.
The survey results have been published
Marie and her team published their findings on Crohn’s disease in the journal Nature. Scientific ReportsThis article is open access and free to read. The research team includes Pierce, Yang, Pankaj Kumar, Jeremy Middleton, William A. Petrie, and Murray. Petrie is a consultant for TECHLAB Inc. and Murray is a consultant for Merck Inc.
This research was supported by the Bill & Melinda Gates Foundation grant OP1136759.
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University of Virginia Health System
Journal References:
Pierce, R. etc (2024) Persistent abnormalities in duodenal microbiota in pediatric Crohn’s disease patients with controlled inflammation after resolution. Scientific Reportsdoi.org/10.1038/s41598-024-63299-y.