Enteric neurons across sites and perturbations. Credit: Science (2025). DOI: 10.1126/science.adr3545

The enteric nervous system (ENS) is a vast network of nerves built into the walls of the intestine. While it is well known for its role in regulating digestion and the movement of food through the intestine, researchers are learning that its influence extends much further.

Ramnik Xavier, MD, Ph.D., of the Department of Molecular Biology at Massachusetts General Hospital, is the senior author of a paper published in Science, “Regional encoding of enteric nervous system responses to microbiota and type 2 inflammation,” that adds to accumulating evidence showing that the ENS works closely with the immune system to help the body respond to bacteria, parasites and allergens.

Far from serving only as the gut’s control center for digestion and movement, the ENS also plays a key role in how the body maintains balance and protects itself from harm.

The gastrointestinal tract is constantly challenged by changes driven by the microbiota, pathogens and the immune system. However, scientists still know little about how the network of nerves in the gut that comprises the ENS responds to these shifting conditions, partly because it has been hard to study these neurons in detail.

To address this, the researchers investigated mouse models with distinct, carefully selected gut microbiomes and others exposed to allergens or parasitic infections. In each case, the team profiled the ENS across different regions of the intestine to define its responses to these conditions.

The researchers used a special type of mouse model with a fluorescent tagging system that made the nuclei of enteric neurons glow. This allowed them to identify and sort neurons from the rest of the gut tissue and study the nuclei of these cells one-by-one to understand their genetic activity.

This approach enabled the investigators to see which genes were active in each cell—in fact, they detected over 6,000 genes per neuron, on average, including lowly expressed genes that can be hard to detect with standard methods.

Additionally, to investigate how these neurons adapt to different conditions, the team used a viral tool to delete specific genes of interest. This process helped to get a clearer picture of which genes control how neurons behave and respond.

Study findings

By studying gene activity in individual neurons of the gut, the team uncovered two main patterns that reveal how diverse and adaptable the ENS is. One group of sensory neurons showed large variations in cell numbers across sites and conditions.

These sensory neurons stood out for their specialized communication, including response signals to many immune molecules produced during allergic responses or parasitic infection. Another group, the motor neurons that control gut movement, showed more gradual shifts in the genes they expressed across different conditions while maintaining stable numbers.

Strikingly, these patterns were seen across very different conditions—from allergy to parasitic infection to germ-free states—suggesting that the gut’s nervous system coordinates its activity to keep the intestine in balance, no matter the challenge.

Together, these findings create the most detailed roadmap to date of how the gut’s nervous system responds to different environmental challenges. The study shows that changes in the activity of enteric neurons are closely linked to how the intestine functions, connecting cellular behavior to broader gut physiology.

By revealing these connections, the researchers say they have laid the foundation for future research into how the ENS supports gut health, as well as what happens when that balance is disrupted in disease.

By charting how enteric neurons change during inflammation, the team now aims to explore if, and how, the gut’s nervous system can directly influence inflammatory responses. To advance therapeutic progress, they will also study patient samples and laboratory-grown gut models to determine how these findings apply to humans.

Last, but not least, because enteric neurons also communicate with other nerves that connect to the brain—influencing appetite, food intake and more—understanding how inflammation-related changes in the ENS affect these wider nerve networks could reveal more about the gut’s role in overall health and disease.

More information: Peng Tan et al, Regional encoding of enteric nervous system responses to microbiota and type 2 inflammation, Science (2025). DOI: 10.1126/science.adr3545

Citation: Researchers map how gut neurons respond to bacteria, parasites and food allergies (2025, October 31) retrieved 31 October 2025 from https://medicalxpress.com/news/2025-10-gut-neurons-bacteria-parasites-food.html

This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.