Faecalibacterium prausnitzii bacteria, Crohn's disease
Credit: Kateryna Kon/Science Photo Library/Getty Images

An undergraduate researcher from the University of Virginia (UVA) has discovered why children with relapsing Crohn’s disease suffer from repeated bouts of symptoms even after they have appeared to recover. The discovery showed that children with relapsing Crohn’s had a persistent disruption of their microbiomes even after their inflammation symptoms had been controlled by treatment.

The research, by undergraduate Rebecca Pierce, with guidance from Chelsea Marie, PhD, of the UVA School of Medicine appears in the Nature journal Scientific Reports.

“The relationship between dysbiosis and inflammation is a long-standing question in Crohn’s disease. Pierce leveraged a pediatric cohort at UVA to show dysbiosis was present even when gut inflammation was controlled,” said Marie, who is also of UVA division of infectious diseases and international health. “Our study suggests that persistent microbial imbalances might be an important factor in the disease course in children.”

Ning-Jiun Jan, PhD, a senior scientist working in the Marie lab, who mentored Pierce during her research said the new findings could provide a key for helping develop better treatments for the debilitating disease and perhaps even provide a route for curing it.

“Currently, the main goal of most Crohn’s disease treatments is to manage symptoms,” Jan said. “This usually means taking different drugs to address inflammation and encourage healing. However, these are not cures, meaning these drugs need to be taken continuously to prevent relapse. Our study found that though the symptoms have been alleviated the bacterial composition in their guts did not return to normal, which may be why these patients relapse.”

For this study, Pierce, who is now enrolled as a medical student at Georgetown University, and collaborators collected biopsy samples from the intestines of children with Crohn’s who were in remission and from children with no signs of Crohn’s as the control group. Comparison of the microbiomes showed significant differences between the Crohn’s group and healthy controls, with the Crohn’s cohort showing much lower levels of bacteria such as Streptococcus, while others such as Oribacterium—which has previously been lined to gut microbiome disruptions—were increased. There were also notable changes in immune cells of the Crohn’s group, notably an increase in the number of CD4+ T cells, which play a role in inflammation.

The researchers also found that the Crohn’s children exhibited stronger epithelial cell barriers lining their intestines, which suggests that existing treatments are providing some level of therapeutic effect, while not necessarily treating the underlying issues that drive the disease.

“Even in our cohort of pediatric Crohn’s patients in remission, we detected persistent microbial imbalances and subtle inflammatory changes,” Pierce noted. “Current therapeutics have focused on treating clinical symptoms which can leave patients vulnerable to relapse. Our work suggests that incorporating therapies that target the root causes of dysbiosis could lead to improved treatments with fewer relapses.”

These findings suggest that a possible new treatment route for Crohn’s disease could target restoring balance in a patient’s microbiome using fecal transplants or via “cocktails” of healthy microbes tailored to replace those that have been lost due to the disease.

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