Gut Neurons and Immune-Regulating Molecules Combat Inflammation

Recent research from Weill Cornell Medicine reveals that neurons within the gut, part of the enteric nervous system often called the "second brain," produce a molecule that is crucial in modulating the body's immune response during inflammation. This discovery highlights a previously underappreciated neuro-immune communication pathway that influences intestinal health.

The enteric nervous system, composed of hundreds of millions of neurons, orchestrates vital gut functions including digestion, nutrient absorption, and blood flow regulation. While its role in fundamental physiological processes is well understood, its involvement in controlling inflammatory responses has remained less clear.

In the study published in Nature Immunology, scientists focused on group 2 innate lymphoid cells (ILC2s), immune cells residing in the gut lining that contribute to tissue repair and healing. They found that these cells can receive signals from neurons through a molecule called adrenomedullin 2 (ADM2). The production of ADM2 by gut neurons was shown to expand the population of ILC2s and promote tissue protection.

Applying ADM2 in preclinical models resulted in a reduction of inflammation and a boost in tissue healing, suggesting potential for therapeutic interventions. Conversely, impairing ADM2 signaling worsened inflammation, emphasizing the molecule’s protective role.

Further analysis of human tissues from patients with inflammatory bowel disease (IBD) revealed elevated levels of ADM2 compared to healthy controls. Human ILC2s exposed to ADM2 produced higher levels of amphiregulin, a growth factor involved in tissue repair, indicating that this neuro-immune pathway is relevant in human disease.

Lead researcher Dr. Jazib Uddin emphasized the significance of these findings, noting that the enteric nervous system’s role in resolving intestinal inflammation has historically been overlooked. He described the potential for neuro-immune interactions to serve as novel targets for treating bowel diseases.

The study also included translational research involving blood and tissue samples, confirming that the neuro-immune dialogue observed in mice is active in humans. Dr. David Artis, senior author and director of the Jill Roberts Institute for Research in Inflammatory Bowel Disease, highlighted that understanding how the immune and nervous systems communicate could pave the way for innovative therapies that modulate inflammation and promote healing via the enteric nervous system.

This research opens exciting possibilities for developing new treatments for inflammatory bowel disease and other gut-related inflammatory disorders, focusing on the neuro-immune interface as a promising therapeutic target.

source: https://medicalxpress.com/news/2025-08-gut-neurons-body-inflammation-immune.html