Stimulating the vagus nerve to combat intestinal inflammation in IBD

Summary: Researchers have found that stimulating the vagus nerve can reduce intestinal inflammation and improve outcomes in inflammatory bowel disease (IBD). The study reveals how electrical stimulation of this brain-gut nerve influences SUMOylation, a cellular process that drives immune responses, to alleviate symptoms and promote healing.

This approach offers hope for therapies directly targeting inflammation, circumventing the limitations of current treatments. With cases of IBD on the rise, this breakthrough suggests that bioelectronic medicine could be a game-changer in the management of this chronic disease.

Key facts:

• Stimulating the vagus nerve in stressed mice with colitis reduced inflammation, improved symptoms and increased survival rates.
• Targeting SUMOylation, a process involved in immune regulation, mimics the effects of nerve stimulation to reduce intestinal inflammation.
• Cases of IBD have increased by 50% over the past 15 years, affecting nearly 7 million people worldwide.

Source: Duke University

Researchers at Duke University School of Medicine have discovered that harnessing the nervous system could help reduce intestinal inflammation that causes inflammatory bowel disease (IBD).

A new study led by Luis Ulloa, PhD, and Wei Yang, PhD, reveals how electrical stimulation of the vagus nerve, a major nerve connecting the brain and gut, can combat stress-related inflammation that worsens symptoms of IBD. The study highlights the role of the brain in gut health.

Published in Scientific translational medicineDuke is looking to stimulate the vagus nerve in stressed mice with colitis, a form of IBD, which significantly reduced inflammation, alleviated symptoms and improved survival rates.

By mobilizing the parasympathetic nervous system, the team observed that inflammation could be attenuated by controlling SUMOylation, a cellular process that shapes the immune response.

Modulating SUMOylation, either through vagal nerve stimulation or treatment with a SUMOylation inhibitor, could open the door to IBD therapies focused on direct management of inflammation, rather than relief symptoms.

In 2022, Duke researchers, supported by the National Institutes of Health, began studying whether vagus nerve stimulation could affect SUMOylation and trigger a natural anti-inflammatory response that calms immune responses and reduces inflammation.

The new study is the first to show that targeting specific forms of SUMOylation could prevent the harmful influx of immune cells that can trigger intestinal inflammation.

The first study’s author and former Duke researcher, Ayman Youssef, MD, an autonomous biology researcher at Vanderbilt Medical Center, analyzed data identifying that inhibition of SUMOylation, through genetic or drug approaches, significantly slowed disease progression in mouse models.

“A surprising finding from this study is that inhibition of SUMOylation appears to mimic the beneficial effects of vagal stimulation, leading to improvement in clinical symptoms of colitis,” said Yang, professor of anesthesiology and associate professor of neurology at the Duke School of Medicine.

IBD cases are exploding: a 50% increase in the last 15 years. Scientists are stepping up efforts to reduce inflammation-causing cells in the intestines and improve treatment options for nearly 7 million affected people worldwide.

IBD includes two main types: ulcerative colitis, which affects the colon, and Crohn’s disease, which can inflame any part of the digestive tract. These two pathologies disrupt life and can lead to serious complications such as colon perforation, cancer and even early mortality.

Current anti-inflammatory treatments provide relief, but are often insufficient, as patients can lose their response to these medications over time, experience relapses, and experience significant side effects.

Researchers have long noted that stress plays a significant role in exacerbating IBD symptoms, and some have even described ulcerative colitis as psychosomatic.

“Stimulation of the vagus nerve neutralized the effects of stress and restored a balanced and healthy physiological state,” said Ulloa, an anesthesiology researcher at Duke and corresponding author of the study.

“Many relaxation techniques, such as deep breathing and meditation, are designed to enhance the parasympathetic system, with the vagus nerve playing a central role in relaxing most of our organs.

“Although previous studies have suggested the role of the vagus nerve, our study demonstrates that its effect is through the regulation of SUMOylation,” he said.

Ulloa cautions that not all patients may respond the same way and that translating the results of laboratory studies into the clinical setting could lead to variable results or even no benefit. The approach, called “bioelectronic medicine,” is part of an emerging field in which nerve stimulation is being explored to treat a variety of inflammatory conditions ranging from rheumatoid arthritis to Crohn’s disease.

Additional authors: Ata Ur Rehman, Mohamed Elebasy, Jatin Roper of Duke School of Medicine; Shehzad Z. Sheikh of the University of North Carolina Chapel Hill and Jorn Karhausen of the Duke and Humanitas Research Hospital.

Funding: Funding for the study was provided by the NIH National Center for Complementary and Integrative Health (AT011387), the National Institute of Diabetes, Digestive and Kidney Diseases (P01DK094779, 1R01DK104828, and P30-DK034987), and the Helmsley Charitable Trust.

About this neurotechnology and IBD research news

Author: Shantell M. Kirkendoll
Source: Duke University
Contact: Shantell M. Kirkendoll – Duke University
Picture: Image is credited to Neuroscience News

Original research: The results will appear in Scientific translational medicine