Early source of irritable bowel syndrome discovered

June 14, 2018, Michigan State University
Early source of irritable bowel syndrome discovered
NK2R (green) and enteric glial (blue) are keys to achieving “intestinal happiness.” Credit: Michigan State University

Michigan State University scientists have identified an early cause of intestinal inflammation, one of the first stages of inflammatory bowel disease and irritable bowel syndrome, which afflict around 11 percent of the world's population.

The discovery, featured in the current issue of Cellular and Molecular Gastroenterology and Hepatology, points to communication between sensory in the gut and a class of non-neuronal cells – enteric glia – as the culprits.

"The gut has its own brain and that has more neurons in the intestines than in the spinal cord. Within your intestines lies a 'second brain' called the enteric nervous system," said Brian Gulbransen, MSU neuroscientist and the study's senior author. "The enteric nervous system is an exceedingly complex network of neural circuits that programs a diverse array of gut patterns and is responsible for controlling most gastrointestinal functions."

Accompanying the neurons in this second brain are enteric glia, which are responsible for regulating inflammation. The disruption of neural circuits in the gut by inflammation is considered an important factor in the development of and .

The research team pinpointed that before the first hints of intestinal pain or rumblings, specific molecular changes spark the discomfort. Tachykinins, peptides that are keys to pain transmission and intestinal contractions, drive enteric neuroinflammation.

The gut's major source of tachykinins are enteric neurons. Tachykinins drive neuroinflammation in the gut through a "multicellular cascade" of enteric neurons, bead-like TRPV1-positive nerve fibers and enteric glia.

Early source of irritable bowel syndrome discovered
MSU scientists have identified an early cause of intestinal inflammation, one of the first stages of inflammatory bowel disease and irritable bowel syndrome, which afflict around 11 percent of the world?s population. Credit: Michigan State University

Gulbransen's team revealed that glial cells, once thought to be supporting cells, are active signaling cells involved in much of the cross-talk that happens in the gut. The key is isolating a single voice rather than stifling the entire cacophony, Gulbransen said.

"Post inflammation, there are still many angry glial cells. Because they've amped up their signaling, they make you, and your gut, more sensitive," Gulbransen said. "We hope we can turn them back to happy glia, reduce the sensitivity and return gut function to normal."

One of those single voices – the key to intestinal happiness – is NK2R, a receptor that's a critical mechanism in driving neuron-to-glia signaling. The team is just starting to understand the genes involved and inventorying what's being activated and what's not. But NK2R is proving promising.

"By blocking the receptor with GR 159897, which is a known NK2 receptor antagonist drug, it disconnected the signaling between neurons and glia," he said. "It proved to be quite effective in accelerating recovery from inflammation."

This foundation could lead to more targets that could be treated with drugs that would reset the sensitivity of these neurons.

MSU scientists, including Ninotchska Delvalle, Christine Dharshika, Wilmarie Morales-Soto, David Fried and Lukas Gaudette, all contributed to this study.

Explore further: Understanding the architecture of our 'second brain'

Related Stories

Understanding the architecture of our 'second brain'

May 19, 2017
Scientists have made an important step in understanding the organisation of nerve cells embedded within the gut that control its function - a discovery that could give insight into the origin of common gastrointestinal diseases, ...

Lower levels of antioxidants may lessen damage from colitis

September 29, 2017
A new study finds that lowering the levels of an antioxidant in the colon has an unexpectedly positive effect on gastrointestinal (GI) inflammation. The paper is published ahead of print in the American Journal of Physiology—Gastrointestinal ...

'Second brain' neurons keep colon moving

May 29, 2018
Millions of neurons in the gastrointestinal tract coordinate their activity to generate the muscle contractions that propel waste through the last leg of the digestive system, according to a study of isolated mouse colons ...

A gut feeling about neural stem cells

February 1, 2013
Proper function of the digestive system requires coordinated contraction of the muscle in the wall of the intestinal tract, regulated by the enteric nervous system. Damage or loss of these neurons can result in intestinal ...

Small molecule protects the nervous system's support cells from excessive stimulation

October 5, 2017
Glutamate is the primary excitatory neurotransmitter of the central nervous system, in excess it causes cells to become overexcited, which contributes to neuron death in neurodegenerative disease. Now, a study of flies led ...

Recommended for you

Breakthrough treatment for crippling jaw disease created

June 20, 2018
A first-ever tissue implant to safely treat a common jaw defect, known as temporomandibular joint dysfunction, has been successfully tested by UCI-led researchers in a large animal model, according to new findings.

New flu vaccine only a little better than traditional shot

June 20, 2018
A newer kind of flu vaccine only worked a little bit better in seniors this past winter than traditional shots, the government reported Wednesday.

Blood signature could improve early tuberculosis diagnosis

June 19, 2018
A gene signature in the bloodstream could reveal whether someone is going to develop active tuberculosis (TB) disease months before symptoms begin. Such a signature has now been developed by a team led by the Francis Crick ...

Scientists uncover a factor important for Zika virus host species restriction

June 19, 2018
Princeton University researchers Qiang Ding, Alexander Ploss, and colleagues have identified one of the mechanisms by which Zika virus (ZIKV) circumvents immune control to replicate in human cells. The paper detailing this ...

Toothpaste and hand wash may contribute to antibiotic resistance

June 19, 2018
A common ingredient in toothpaste and hand wash could be contributing to antibiotic resistance, according to University of Queensland research.

Children's immune system could hold the key to preventing sepsis

June 19, 2018
Children's immune systems could hold the key to preventing life-threatening infections and sepsis, a new study has revealed.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.