Immune system's balancing act keeps bowel disease in check

October 2, 2018, Walter and Eliza Hall Institute of Medical Research
Immune system's balancing act keeps bowel disease in check
Dr Alan Yu and Associate Professor Seth Masters. Credit: Walter and Eliza Hall Institute of Medical Research

Australian researchers have uncovered clues in the immune system that reveal how the balance of 'good' gut bacteria is maintained. The information could help in the prevention and treatment of inflammatory bowel disease (IBD).

The study, published in the journal Nature Communications, showed that the increased presence of a protein responsible for sensing infection – called NLRP1 – meant there were fewer and anti-inflammatory molecules in the gut, leading to higher levels of inflammation and an increased risk of IBD.

The research was led by Associate Professor Seth Masters, Dr. Tracy Putoczki and Dr. Alan Yu from the Walter and Eliza Hall Institute, in collaboration with researchers at University of Melbourne's Bio21 Institute in Melbourne and a team led by Dr. Graham Radford-Smith from QIMR Berghofer Medical Research Institute in Queensland.

Getting to the bottom of IBD

The cause of IBD, which includes Crohn's disease and ulcerative colitis, is not well understood. A better understanding could improve treatment options and the quality of life for patients, who often experience chronic and debilitating symptoms.

Associate Professor Masters said while it was known that the immune system could defend the gut from bad bacteria, its role in maintaining 'good' bacteria wasn't appreciated until now.

"We have uncovered the immune system's ability to regulate good through the immune sensor NLRP1. Good bacteria are important because they help to produce butyrate – a molecule that dampens inflammation in the body. So understanding how the balance of good bacteria is maintained could one day help to inform preventions and treatments for inflammatory diseases like IBD," he said.

Clues to a cause

Associate Professor Masters said the researchers had discovered the significance of NLRP1 by analysing donated bowel biopsies from patients with IBD, as well as in preclinical models in the laboratory.

"We consistently observed that higher levels of NLRP1 in inflamed areas of the bowel correlated with lower levels of good bacteria and increased inflammation," he said. "And in cases where we genetically deleted NLRP1, levels of inflammation went down.

"Too much NLRP1 leads to an overproduction of a signalling molecule called IL-18 that tells the body to mount a protective response against the threat of colonisation by bad bacteria – but as a consequence the good bacteria and their anti-inflammatory products are also lost. Inflammation occurs as part of this process so when too much IL-18 is produced, inflammation can continue unchecked and cause significant damage to the gastrointestinal tract," he said.

Keeping a healthy balance

The exact triggers for the increase in NLRP1 were unclear but Associate Professor Masters said the new findings enabled researchers to continue along a promising track towards resolving such questions.

"While we don't know exactly what the genetic, microbial or environmental triggers for NLRP1 are, it is clear that faulty regulation of NLRP1 is an underlying cause of IBD.

"Following on from the clues in our study, it may be possible to develop a drug that inhibits IL-18 or targets NLRP1 to block any unchecked inflammation. It's all about helping the immune system keep up the balancing act between all the factors that are constantly interacting to fight disease and promote wellbeing.

"By stopping overproduction of NLRP1 or IL-18 in patients with IBD we may be able boost the number of good and anti-inflammatory properties in the gut and help to prevent or fight the damaging effects of too much ," he said.

Explore further: Genetic malfunction causes hyperactive inflammation and cancer susceptibility

More information: Hazel Tye et al. NLRP1 restricts butyrate producing commensals to exacerbate inflammatory bowel disease, Nature Communications (2018). DOI: 10.1038/s41467-018-06125-0

Related Stories

Genetic malfunction causes hyperactive inflammation and cancer susceptibility

May 17, 2017
Mutations in an immune gene underlie two inflammatory skin diseases, according to research led by A*STAR scientists. These findings reveal a mechanism that could control inflammation and offer routes to investigate it further.

'Sensor' protein could help fight against obesity and diabetes

October 22, 2015
Melbourne researchers have identified an internal 'sensor' that helps fight obesity by instructing cells to burn their fat stores. The finding could play a major role in the fight against obesity and metabolic diseases, including ...

How good bacteria can help keep a gut healthy

July 3, 2018
New research reveals a cellular mechanism by which good bacteria can help the gut stay healthy. The study, which appears in the journal Immunity, shows that good bacteria, or the microbiota, interact with both the epithelial ...

'Good' bacteria is potential solution to unchecked inflammation seen in bowel diseases

March 13, 2017
Beneficial bacteria may be the key to helping to reverse a cycle of gut inflammation seen in certain inflammatory bowel diseases, University of North Carolina Lineberger Comprehensive Cancer Center researchers have found.

Immune system kill switch could be target for chemotherapy and infection recovery

December 6, 2012
Researchers have discovered an immune system 'kill switch' that destroys blood stem cells when the body is under severe stress, such as that induced by chemotherapy and systemic infections.

Recommended for you

Some brain tumors may respond to immunotherapy, new study suggests

December 10, 2018
Immunotherapy has proved effective in treating a number of cancers, but brain tumors have remained stubbornly resistant. Now, a new study suggests that a slow-growing brain tumor arising in patients affected by neurofibromatosis ...

A code for reprogramming immune sentinels

December 10, 2018
For the first time, a research team at Lund University in Sweden has successfully reprogrammed mouse and human skin cells into immune cells called dendritic cells. The process is quick and effective, representing a pioneering ...

Major breakthrough in quest for cancer vaccine

December 6, 2018
The idea of a cancer vaccine is something researchers have been working on for over 50 years, but until recently they were never able to prove exactly how such a vaccine would work.

Newly identified T cells could play a role in cancer and other diseases

December 6, 2018
Researchers from the UCLA Jonsson Comprehensive Cancer Center and the La Jolla Institute for Immunology have identified a new type of T cell called a phospholipid-reactive T cell that is able to recognize phospholipids, the ...

Classifying brain microglia: Which are good and which are bad?

December 6, 2018
Microglia are known to be important to brain function. The immune cells have been found to protect the brain from injury and infection and are critical during brain development, helping circuits wire properly. They also seem ...

Memory B cells in the lung may be important for more effective influenza vaccinations

December 5, 2018
Seasonal influenza vaccines are typically less than 50 percent effective, according to Centers for Disease Control and Prevention studies. Research at the University of Alabama at Birmingham, published this week in Nature ...

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.