Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Macrophages treated with the short-chain fatty acid butyrate – a by-product of dietary fibre breakdown - are better equipped to fight bacteria in the gut, report researchers from the Kennedy Institute and the Translational Gastroenterology Unit. These findings could lead to new strategies to restore gut health in inflammatory bowel disease (IBD).

The research, published in Immunity, shows that macrophages produce more bacteria-busting antimicrobial peptides and clear bacteria faster if treated with butyrate during their development. And when mice were fed butyrate, the animals became more resistant to intestinal infection. 

Butyrate is a naturally occurring short-chain fatty acid produced by gut microbes as they break down dietary fibre. Although previous studies have linked butyrate to gut health, this is the first report to show that butyrate can increase immunity against harmful bacteria in the intestine.

“Importantly, butyrate bolsters macrophage antimicrobial activity without inducing inflammation.” says Kennedy Director Professor Fiona Powrie, who co-led the study together with Professor Holm Uhlig, a Principal Investigator at the Translational Gastroenterology Unit, Oxford.

Fiona adds, “This is particularly exciting in the context of IBD where the butyrate pathway could be targeted to promote beneficial macrophage responses and re-establish homeostasis”.

IBD are chronic painful diseases, which include conditions such as Crohn’s disease and ulcerative colitis, affecting approximately 5 million people worldwide. Defective antimicrobial responses are thought to contribute to IBD, and high numbers of inflammation-promoting macrophages in the gut are linked to severe disease.

Speaking of the research, Holm said “Since the level of butyrate in the gut of patients depends on diet as well as specific members of the microbiota that can metabolise plant fibres into butyrate, this study is potentially not only relevant for treatment but also for understanding how prevention or maintenance of remission can be achieved”.

The team found that butyrate re-wired the metabolism of developing macrophages and activated a distinct set of genes to drive the accumulation of non-inflammatory antimicrobial macrophages.  They went on to show that butyrate mediates these effects by restraining the activity of enzyme histone deacetylase 3 (HDAC3). 

The researchers are now examining intestinal macrophages isolated from IBD patients to understand whether defects in metabolic signalling contribute to the development of disease. 

The ongoing collaboration between the Powrie and Uhlig laboratories is part of a wider partnership between the Kennedy Institute, the Translational Gastroenterology Unit and the MRC Weatherall Institute of Molecular Medicine within the NIHR Oxford Biomedical Research Centre (BRC) Gastroenterology and Mucosal Immunity Theme, which ultimately seeks to drive new therapies and personalised medicine approaches for inflammatory gastrointestinal and skin diseases into the clinic.

The work was funded by the Wellcome Trust, the BBSRC, the Helmsley Charitable Trust, and the Crohn’s & Colitis Foundation, with contribution from the BRC Gastrointestinal biobank supported by the NIHR BRC. 

Similar stories

Furniss Group paper wins journal award

Editors at the Journal of Hand Surgery have recognised the Furniss Group with an award for the best paper published in the Journal in 2022. The Editor’s Award recognises research with scientific importance, outstanding study stringency, and a high academic standard.

NIHR Fellowships awarded to NDORMS researchers

Congratulations to Eileen Morrow and Mae Chester-Jones who have received NIHR Doctoral Fellowships

ORUK Early Career Research Fellowship awarded to NDORMS researcher

Congratulations to Jack Tu who has been awarded an Orthopaedic Research UK Early Career Research Fellowship to explore the cause of knee pain after total knee replacement.

OCTRU - delivering answers to important clinical questions

The Oxford Clinical Trials Research Unit (OCTRU) has received NIHR benchmarking results and offers excellent value for money according to the report

Unhelpful thoughts about fracture symptoms hinder recovery

The importance of mindsets and feelings about fracture symptoms have been shown to be a key factor in recovery of musculoskeletal conditions.

Fat tissues can play a protective role against inflammation in the intestine

A new study in The EMBO Journal has revealed how fat tissues might provide a protective role in intestinal inflammation opening new lines of research into the treatment of inflammatory bowel diseases.