A recent study indicates that stimulating the vagus nerve in mice with colitis can alleviate stress-induced symptoms of inflammatory bowel disease (IBD) by influencing SUMOylation, a cellular immune response that promotes gut inflammation.
Researchers from Duke University School of Medicine have discovered that engaging the nervous system may help lessen gut inflammation associated with inflammatory bowel disease (IBD).
The study, led by Luis Ulloa, PhD, and Wei Yang, PhD, highlights how electric stimulation of the vagus nerve, which serves as a vital link between the brain and gut, can address inflammation connected to stress that exacerbates IBD symptoms.
As published in Science Translational Medicine, the research demonstrated that stimulating the vagus nerve in stressed mice suffering from colitis, a type of IBD, decreased inflammation, improved symptoms, and increased survival rates. By activating the parasympathetic nervous system, the researchers found that inflammation could be mitigated by inhibiting SUMOylation, a process that modulates immune responses.
By altering SUMOylation—either through vagus nerve stimulation or the use of SUMOylation inhibitors—new avenues for IBD treatment that target inflammation directly could potentially be realized, rather than just focusing on symptom relief.
Starting in 2022, Duke researchers, supported by the National Institutes of Health, examined whether vagus nerve stimulation could influence SUMOylation to ignite a natural anti-inflammatory response, thereby helping to cool down immune system reactions and reduce inflammation.
This recent study is the first to indicate that manipulating specific variants of SUMOylation can thwart the harmful influx of immune cells that provoke gut inflammation. Ayman Youssef, MD, the first author and a former Duke scholar, evaluated data showing that hindering SUMOylation through genetic or pharmacological methods significantly slowed down disease progression in mouse models.
“A surprising aspect of this study is that blocking SUMOylation seems to replicate the favorable outcomes of vagal stimulation, leading to better clinical symptoms of colitis,” noted Yang, a professor of anesthesiology and associate professor of neurology at Duke School of Medicine.
The prevalence of IBD has surged, with cases rising by 50% over the past 15 years. Researchers are working diligently to decrease inflammation-triggering cells in the intestines and enhance treatment options for the approximately 7 million individuals affected globally.
IBD comprises two main forms: ulcerative colitis, which targets the colon, and Crohn’s disease, which can cause inflammation throughout any section of the digestive system. Both conditions can disrupt daily life and may result in severe complications, such as colon perforation, cancer, and early death.
While current anti-inflammatory treatments provide some relief, they often have limitations; patients can develop a diminished response to these therapies over time, face relapses, and endure considerable side effects.
Researchers have long recognized that stress substantially aggravates IBD symptoms, with some describing ulcerative colitis as psychosomatic.
“Stimulating the vagus nerve countered the impacts of stress and restored a healthy physiological balance,” remarked Ulloa, leading researcher and corresponding author of the study. “Numerous relaxation practices, such as deep breathing and meditation, aim to enhance the parasympathetic system, where the vagus nerve plays a crucial role in organ relaxation.”
“Although earlier research has indicated a potential role for the vagus nerve, our findings illustrate that its effects are mediated through the regulation of SUMOylation,” he said.
Ulloa cautions that responses may vary among patients, and applying laboratory findings in clinical settings could yield differing results or no positive effect at all. This method, termed “bioelectronic medicine,” is part of a developing field examining nerve stimulation as a treatment avenue for various inflammatory disorders, including rheumatoid arthritis and Crohn’s disease.
Additional Contributors: Ata Ur Rehman, Mohamed Elebasy, Jatin Roper of Duke School of Medicine; Shehzad Z. Sheikh from the University of North Carolina at Chapel Hill; and Jorn Karhausen from Duke and Humanitas Research Hospital.
Financial backing for the study was provided by the NIH National Center for Complementary and Integrative Health (AT011387), National Institute of Diabetes, Digestive and Kidney Diseases (P01DK094779, 1R01DK104828, and P30-DK034987), along with the Helmsley Charitable Trust.
