Novel molecules to combat asthma and covid-related lung diseases discovered

January 25, 2021

A study designed to study how the immune system impacts gut bacteria - has led to the extraordinary discovery of two molecules that can not only provide profound protection in experimental models of asthma but can also substantially reduce the severity of an attack.

Neither of these molecules, one of which is already commercially available as a dietary supplement, were previously known to have an effect on asthma - and they also appear, from animal studies, to have a role in treating the respiratory illness that is prevalent, and often fatal, in people with serious COVID-19.

The researchers aim to test one of the molecules in a clinical trial in 2021 in asthmatics.

As further evidence that these two molecules could potentially protect against asthma the Monash University researchers found, through studying the literature, that these metabolites are present in higher amounts in two studies of children without asthma compared to those with the disease, according to Professor Benjamin Marsland from the Monash University Central Clinical School, whose paper is published today in Nature Immunology.

Asthma is one of the most common major non-communicable diseases and it impacts 300 million people globally. The global asthma treatment market size stood at over $18 billion US in 2019.

The team led by VESKI innovation fellow, Professor Marsland, wanted to understand how the immune system impacts the gut microbiome. While it is known that gut bacteria have an effect on the immune system, "how the immune system influences the gut microbiome has to date been under studied," he said.

Studying a mouse that had a limited immune system, consisting of a single type of antibody, the researchers found the gut microbiome was changed. By transferring these gut bacteria into 'normal' mice they could identify which bacteria had an impact on the mouse immune system.

In what was an enormous surprise the researchers found that the production of a particular gut bacteria by-product, called p-cresol sulfate (PCS), led to a "profound and striking protection against asthma." Part of the serendipity of the finding is that Professor Marsland's area of expertise is in the immunology of asthma, though he suspects this metabolite may have a role in other inflammatory diseases.

The researchers found that the PCS was produced by enhanced bacterial metabolism of L-tyrosine; a well-known amino acid found in dietary supplements aimed at improving attention and alertness.

"We found that giving mice either L-tyrosine or PCS, provided significant protection against lung inflammation. PCS travels all the way from the gut, to the lungs, and acts on epithelial cells lining the airways to prevent the allergic asthma response"

The researchers also tested the metabolites in animal models of acute respiratory distress syndrome (ARDS), and found it to be protective. ARDS is a common killer of people with serious COVID-19.

While L-tyrosine has a long history of use in the clinic, as mentioned in dietary supplements, its potential use as a therapy could be fast tracked into clinical trials because it is known to be safe. Professor Marsland commented "It's very important that a thorough clinical study is performed in order to determine whether L-tyrosine is effective in people with asthma, and for us to determine what is the correct dose and treatment regime."

PCS however is known to be in high levels in people with chronic kidney disease and it's suspected to be toxic because of these patient's inability to clear it. The research group has started developing a form of PCS that is a potent protector against asthma without the potential toxic side effects.

More importantly the scientists have found that inhaling PCS provides a direct protective effect against lung inflammation, opening the way for a novel inhaled preventive therapy.
-end-


Monash University

Related Asthma Articles from Brightsurf:

Breastfeeding and risks of allergies and asthma
In an Acta Paediatrica study, exclusive breastfeeding for the first 3 months was linked with a lower risk of respiratory allergies and asthma when children reached 6 years of age.

Researchers make asthma breakthrough
Researchers from Trinity College Dublin have made a breakthrough that may eventually lead to improved therapeutic options for people living with asthma.

Physics vs. asthma
A research team from the MIPT Center for Molecular Mechanisms of Aging and Age-Related Diseases has collaborated with colleagues from the U.S., Canada, France, and Germany to determine the spatial structure of the CysLT1 receptor.

New knowledge on the development of asthma
Researchers at Karolinska Institutet in Sweden have studied which genes are expressed in overactive immune cells in mice with asthma-like inflammation of the airways.

Eating fish may help prevent asthma
A scientist from James Cook University in Australia says an innovative study has revealed new evidence that eating fish can help prevent asthma.

Academic performance of urban children with asthma worse than peers without asthma
A new study published in Annals of Allergy, Asthma and Immunology shows urban children with poorly controlled asthma, particularly those who are ethnic minorities, also suffer academically.

Asthma Controller Step Down Yardstick -- treatment guidance for when asthma improves
The focus for asthma treatment is often stepping up treatment, but clinicians need to know how to step down therapy when symptoms improve.

Asthma management tools improve asthma control and reduce hospital visits
A set of comprehensive asthma management tools helps decrease asthma-related visits to the emergency department, urgent care or hospital and improves patients' asthma control.

Asthma linked to infertility but not among women taking regular asthma preventers
Women with asthma who only use short-acting asthma relievers take longer to become pregnant than other women, according to research published in the European Respiratory Journal.

What are the best ways to diagnose and manage asthma?
A team of experts from The University of Texas Medical Branch at Galveston examined the current information available from many different sources on diagnosing and managing mild to moderate asthma in adults and summarized them.

Read More: Asthma News and Asthma Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.