Strategic Research Centre: Restoring balance in the gut for less inflammation in the lungs

Find out how Professor Daniel Peckham at the University of Leeds and a team of experts from around the world are looking for the link between the balance of bacteria in the gut of a person with cystic fibrosis and the degree of lung inflammation they experience during an infection.

Here’s a simple summary of the work – read on for more detail.



When we talk about bacteria, it’s usually bad news. However, this Strategic Research Centre is investigating the benefits of a healthy balance of good bacteria!



You have many different species of bacteria in your gut, which help to digest your food. The number and type of each species present seems to have an impact on the health of many parts of the human body. Various factors can affect these bacteria, including the use of antibiotics (such as those used to treat lung infections), as well as the levels of chemicals called ‘short chain fatty acids’ present in the gut. These are produced when certain types of fibre in your food are broken down by the bacteria. 



This research aims to investigate exactly how levels of short chain fatty acids and antibiotics affect the bacteria in the gut of people with CF, and if this has any effect on inflammation in the lungs, as well as looking at options for amending the diet of people with CF to help return the range of gut bacteria present to a healthy balance.



Now for the scientific detail!

Background

The human gut contains billions of bacteria from hundreds of species; the collection of species is referred to as the gut 'microbiome'. The right combination of bacteria is essential for maintaining health, and changes in the species present can influence lung inflammation. In animal studies this occurs through the production of chemicals called ‘short chain fatty acids’ (SCFAs) by particular gut bacteria that break down fibre in the diet. SCFAs affect immune cells and influence inflammation and lung damage.  



In cystic fibrosis (CF), the gut microbiome is severely disturbed due to the effect of the presence of abnormal CFTR protein, antibiotic use, diet and proton pump inhibitors (a treatment for acid reflux). Increasing SCFAs and altering the gut microbiome could have the potential to reduce lung inflammation and improving lung health. 

How it will work

Led by Professor Daniel Peckham, University of Leeds, this SRC will study the relationship between decline in lung function, gut microbiome and gut SCFA levels in people with CF, and, using a murine model, will investigate the influence of SCFAs on lung responses during infection. The influence of antibiotics and SCFAs on the CF gut microbiome will be explored, using a novel human gut model, and analysis of the effect of SCFAs on immune cells. A study to examine the effect of adding SCFAs and/or fermentable fibre to the diet on inflammation in the lungs.



There is a real clinical need to evaluate the influence of diet and antibiotics on the CF gut microbiome, and determine how these changes influence inflammation in the lung and rest of the body. This collaborative research is topical, highly relevant to people with CF and gives centres of excellence the opportunity to share their knowledge and expertise with each other. 

What are the aims?

This research group will seek to:

• Gather a better understanding of the gut microbiome and SCFA levels in patients with CF;  
• Understand the influence of antibiotics, diet (particularly fermentable fibre), and SCFAs and other metabolites on gut microbiome in mouse and human gut models;   
• Work out what influence SCFAs have on lung responses in a mouse model; 
• Determine the mechanisms by which bacterial products on CF macrophages and neutrophils and their bone marrow precursors at an epigenetic, transcriptional, and functional level.

Lead Principal Investigator (PI): Professor Daniel Peckham (University of Leeds)

Co-PIs: 

• Professor Andres Floto (University of Cambridge)
• Professor Benjamin Marsland (Monash University, Melbourne, Australia)
• Dr Jeffrey Barrett (Wellcome Trust Sanger Institute)
• Dr Helen White (Leeds Beckett University)
• Professor Mark Wilcox (University of Leeds)
• Professor David Jayne (University of Leeds)

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