Duke University School of Medicine researchers have found that harnessing the nervous system could help reduce intestinal inflammation that drives inflammatory bowel disease (IBD). A new study led by Luis Ulloa, PhD, and Wei Yang, PhD, shows how electrical stimulation of the vagus nerve – a major nerve that connects the brain and gut – can combat the stress-induced inflammation that exacerbates IBD symptoms.
Vagus Nerve Stimulation Reduces Intestinal Inflammation by Modulating the Immune Response
The study, published in Science Translational Medicine, showed that stimulating the vagus nerve in stressed mice with colitis, a form of IBD, reduced inflammation, improved symptoms and increased survival. By activating the parasympathetic nervous system, the team observed that inflammation can be alleviated by inhibiting SUMOylation, a cellular process that influences the immune response. Modulation of SUMOylation – either through stimulation of the vagus nerve or treatment with a SUMOylation inhibitor – could pave the way for IBD therapies that focus on directly treating inflammation rather than just alleviating symptoms.
In 2022, with support from the National Institutes of Health, Duke University researchers began investigating whether stimulating the vagus nerve 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 study’s first author and former Duke University research fellow, Dr. Ayman Youssef, a clinical associate in autonomy at Vanderbilt Medical Center, analyzed data showing that inhibiting SUMOylation through genetic or drug approaches dramatically slowed disease progression in mouse models.”A surprising finding of this study is that inhibition of SUMOylation appears to mimic the beneficial effects of vagal stimulation, leading to improvement in the clinical symptoms of colitis,” said Yang, professor of anesthesiology and associate professor of neurology at Duke School of Medicine.
“Bioelectronic Medicine” is Part of an Emerging Field of Research
Cases of IBD are increasing rapidly – by 50% in the last 15 years. Scientists are increasingly working to reduce inflammation-causing cells in the gut and improve treatment options for the nearly 7 million people affected worldwide. IBD comprises two main types: Ulcerative colitis, which affects the colon, and Crohn’s disease, a disease that can inflame any part of the digestive tract. Both diseases affect lives and can lead to serious complications such as bowel perforations, cancer and even premature mortality. While current anti-inflammatory treatments provide relief, they often fall short as patients stop responding to these medications over time, suffer 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. By stimulating the vagus nerve, the effects of stress were neutralized, according to researchers, and a balanced and healthy physiological state was restored. Many relaxation techniques, such as deep breathing and meditation, are designed to strengthen the parasympathetic system, with the vagus nerve playing a central role in relaxing most of our organs.
Although previous studies have pointed to the role of the vagus nerve, this study shows that its effect is mediated through the regulation of SUMOylation. However, the researchers caution that not all patients may respond in the same way, and that translating the results of laboratory studies to clinical situations could lead to different results or no benefit at all. The approach, known as “bioelectronic medicine”, is part of an emerging field of research exploring nerve stimulation to treat a range of inflammatory diseases from rheumatoid arthritis to Crohn’s disease.