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Centenary Institute - Medical Research
Centenary Institute - Medical Research

Gut microbiome link to deadly lung disease

Research led by the Centenary Institute, the University of Technology Sydney and the University of Queensland has shown for the first time a link between chronic obstructive pulmonary disease (COPD), an often fatal lung condition, and the gut microbiome.

The findings, published in the high impact science journal ‘Nature Communications’, suggest that the gut may be helpful in diagnosing COPD and may also be a potential source of new therapeutic targets to help treat the chronic respiratory disorder.

“It’s already known that the lung microbiome is a contributing factor in COPD,” said Professor Phil Hansbro (pictured), senior author of the study and Director of the Centenary UTS Centre for Inflammation.

“We wanted to see if the gut environment was also somehow involved–to determine whether the gut could act as a reliable indicator of COPD or if it was connected in some way to the development of the disease.”

In the study, the researchers compared the microbiome and metabolite profiles of stool samples from COPD patients with healthy individuals. Revealed were significant differences between the two groups.

COPD patients exhibited increased levels of the bacteria Streptococcus and Lachnospiraceae in their stool samples. Also identified in individuals with COPD was a unique metabolite signature–formed by the chemical by-products of the metabolic process.

“Our research indicates that the gut of COPD patients is notably different from healthy individuals,” said first author on the paper Dr Kate Bowerman, University of Queensland.

“This suggests that stool sampling and analysis could be used to non-invasively diagnose and monitor for COPD,” she said.

The study’s researchers believe that the altered gut microbiome found in COPD patients could also support the gut as a potential target for new treatments.

“The ‘gut-lung axis’ describes the common immune system of the lung and gastrointestinal tract. This means that activity in the gut can impact activity in the lung. Our COPD findings suggest that the gut microbiome should now also be considered when looking for new therapeutic targets to help treat lung disease,” said Professor Hansbro.

COPD, a life threatening inflammatory disorder of the lungs, is the third most common cause of death globally. More than 3 million lives are lost every year to COPD.

Researchers involved in the study were affiliated with The University of Queensland, Hunter Medical Research Institute, University of Newcastle, The Prince Charles Hospital, Centenary Institute and University of Technology Sydney.

Publication: Disease-associated gut microbiome and metabolome changes in patients with chronic obstructive pulmonary disease.

Read more about our COPD related medical research here.

Anti-inflammatory benefits from gut bacteria found in fish and humans

Researchers at the Centenary Institute have found that sensitivity of the immune system to ‘good’ gut bacteria is present in zebrafish, proving that the ability of an animal to benefit from good gut bugs is evolutionarily conserved whether you walk or swim.

The study, published in the science journal ‘Gut Microbes’, was an international effort led by Centenary Institute researchers with collaborators from the Duke University School of Medicine, USA and Macquarie University, Sydney.

Using transparent zebrafish embryos, the researchers found that zebrafish inflammatory immune cells are calmed by the addition of butyrate. Butyrate is an important ‘short chain fatty acid’ molecule that is produced when good bacteria ferment dietary fibre in the gut–it’s widely touted as a treatment for a range of inflammatory diseases in humans.

“We found that butyrate treatment on zebrafish reduced inflammatory markers on important immune cells called macrophages (a type of white blood cell) that are the generals of the immune system and that help fight inflammatory diseases,” said Dr Pradeep Cholan (pictured right), lead author of the study and research officer in the Immune-Vascular Interactions Laboratory in the Centenary Institute’s Tuberculosis Research Program.

“From an evolutionary perspective, the fact that zebrafish neutrophils (another type of white blood cell) use the same receptor as human neutrophils to ‘sense’ butyrate and activate anti-inflammatory benefits, is yet another example of co-evolution between animals and their gut bacteria for mutual benefit,” said senior author of the study Dr Stefan Oehlers (pictured left), Head of the Centenary Institute Immune-Vascular Interactions Laboratory and also affiliated with the Discipline of Immunology and Infectious Diseases at the University of Sydney.

This study underpins a wider body of research at the Centenary Institute using transparent zebrafish embryos to analyse the interactions between animals and their gut bacteria during inflammatory disease states.

“We have been excellent at using zebrafish to find ‘bad’ bacteria that cause or worsen diseases in people, but here we show that these tiny fish could contribute to the finding of ‘good’ bugs or prebiotics that act like a natural ibuprofen,” said Dr Oehlers.

The research was funded by the NHMRC, the NSW Health Early-Mid Career Fellowships Scheme and the University of Sydney.

Publication: Conserved anti-inflammatory effects and sensing of butyrate in zebrafish.

Read the full media release here.

Professor Phil Hansbro on 60 Minutes

Professor Phil Hansbro, Director of the Centenary UTS Centre for Inflammation has featured on the current affairs program 60 Minutes, explaining his critical research on bushfire smoke, its impact on the health of Australians and how his work could potentially lead to new prevention and treatment strategies.

“What we’re trying to do is to work out the important effects of bushfire smoke on your health and how it potentially affects different people in different ways– such as healthy people, people with asthma and emphysema, older people and those who are pregnant and their offspring,” said Professor Hansbro.

“Once we have this knowledge, we can then evaluate possible prevention and treatment measures including use of new anti-inflammatory drugs that may be able to help alleviate the effects of excessive smoke inhalation,” he said.

The full 60 Minutes story, titled ‘The Big Smoke’, can be accessed online (in two parts) via the Nine Network’s website.

A short video of Professor Hansbro on 60 Minutes can also be accessed on Twitter.

Prime 7 News interviews Professor Phil Hansbro

Professor Phil Hansbro, Deputy Director at the Centenary Institute and Director of the Centenary UTS Centre for Inflammation has been interviewed by Prime7 News on his new study that will be focused on exploring the health impacts of people’s exposure to bushfire smoke.

The study, a collaboration between the Centenary Institute and the University of Technology Sydney (UTS), will assess how bushfire smoke affects the airways, lungs and other organs and will determine what the long-term consequences of this exposure could be.

Click here to view the Prime7 news story online.

Click here to find out more about Professor Hansbro and his respiratory and inflammation based research.

COVID-19 research targets human enzymes

Centenary Institute researchers have examined the critical role of human enzymes and the coronavirus in a newly published scientific review article that explores potential strategies for COVID-19 disease treatment and management.

The review article published in the prestigious ‘Journal of Diabetes’, seeks to explain how the human enzyme dipeptidyl peptidase (DPP4), which is a driver of diabetes severity, could be exacerbating COVID-19.

“COVID-19 is more severe in people who have type 2 diabetes, obesity and related chronic diseases,” says Professor Mark Gorrell (Head of the Centenary Institute Liver Enzymes in Metabolism and Inflammation Program) and senior author of the review article.

“We also see more DPP4 made in people with diabetes, obesity and related chronic diseases. Drugs that target DPP4 enzyme activity are regularly taken by many people for type 2 diabetes. Such drugs may have immune system and cardioprotective effects that could be beneficial in COVID-19 cases,” he says.

The review article notes that DPP4, which is known to be the key receptor for the MERS-coronavirus (Middle East respiratory syndrome) might also be an additional or alternate port of entry for SARS-CoV-2 into human cells.

“COVID-19 is caused by the SARS-CoV-2 coronavirus, which is similar to SARS-CoV and MERS-CoV. Each of these viruses attach to and enter human cells by binding to specific human enzymes,” says Professor Gorrell.

“Recent research suggests that SARS-CoV-2 can bind to both DPP4 and the ACE2 enzyme and so have two ways to infect our lungs and gut. Once we fully understand this process, we may be able to develop a drug that can help disrupt this viral activity,” he says.

Professor Gorrell, an expert in human proteases (enzymes that break down proteins) has recently launched a new research program in response to the growing COVID-19 pandemic.

“TMPRSS2 (Transmembrane protease, serine 2) is essential for SARS-CoV and SARS-CoV-2 infection. This protease activates the viral protein on the coronavirus necessary for virus cell entry at the start of viral infection in the human body,” he says.

“We are looking to develop a selective TMPRSS2 inhibitor that is both effective and very safe using our expertise and a unique drug screening approach. The successful development of such an inhibitor could be utilised as a novel therapy for both past and current, and possibly future, SARS-CoV coronaviruses.”

“I’m optimistic that our research will contribute meaningfully to the global COVID-19 health response,” he says.

Read the full media release here.

Further Information on the Centenary Institute’s coronavirus activity can be found here.