A new study reveals how electrical stimulation of the vagus nerve-a major nerve connecting the brain and gut-may combat the stress-related inflammation that worsens inflammatory bowel disease symptoms. Published in Science Translational Medicine, the study showed that vagus nerve stimulation in stressed mice with colitis, a form of inflammatory bowel disease, reduced inflammation, improved symptoms, and boosted survival rates. By engaging the parasympathetic nervous system, the team observed that inflammation could be eased by inhibiting SUMOylation, a cellular process that shapes immune response.
Modulating SUMOylation—either through vagal nerve stimulation or treatment with a SUMOylation inhibitor—could open the door to inflammatory bowel disease therapies that focus on managing inflammation directly, rather than alleviating symptoms.
The new study shows that targeting specific forms of SUMOylation could prevent the harmful influx of immune cells that can trigger gut inflammation. Researchers analyzed data identifying that inhibiting SUMOylation, through genetic or drug-based approaches, dramatically slowed disease progression in mouse models.
Current anti-inflammatory treatments bring relief but often fall short, as patients can lose their response 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.
“Stimulating the vagus nerve neutralized the effects of stress and restored a balanced and healthy physiologic state,” said Ulloa, a Duke researcher, the leading and corresponding author of the study. “Many relaxation techniques, like 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.
Reference: Ayman Youssef et al.,Vagal stimulation ameliorates murine colitis by regulating SUMOylation.Sci. Transl. Med.16,eadl2184(2024).DOI:10.1126/scitranslmed.adl2184
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