Is there a link between the gut microbiome and Behçet syndrome?
Research details
- Type of funding: Clinical Fellowship
- Grant Holder: Dr Liying Low
- Institute: University of Birmingham
- Region: West Midlands
- Start date: November 2016
- End Date: June 2022
- Priority: Causes
- Eye Category: Ocular inflammatory
Overview
Behçet syndrome is a very serious condition that causes swelling (inflammation) and ulcers a various parts of the body. It can lead to blindness and early death. We don’t yet know the specific cause but Dr Low has found that people with Behçet syndrome have more bacterial toxins in their blood samples than people without the condition. These toxins aren’t usually found in the blood. They can only get there via the gut, if the lining of the gut isn’t working as it should. This might be a sign that something is going on in the community of microbes and bacteria that live in the body. Together these are called the microbiome.
New technology means researchers have recently been able to start studying the microbiome. The gut microbiome has been shown to be important for a healthy immune system (the body’s defence against infection). And changes to the gut microbiome can send the immune system into overdrive, leading to inflammation. Gut microbes have also been shown to cause inflammation in the eye.
So in this project Dr Low is looking for changes in the gut microbiome from stool samples from Behçet syndrome patients compared to healthy volunteers. She is also comparing patients with and without a gene called HLA-B*51, which is linked to increased risk of Behçet. Results from the study will help us understand the links between genes and the environment, and whether changing the gut microbiome might be a good approach to treating Beçhet syndrome.-
Scientific summary
Characterising host-microbiome interactions in Behçet’s Disease
Behçet's Disease (BD) is a devastating inflammatory condition of unknown cause, typically occurring
in young adults, leading to blindness and premature death. The pathogenesis of BD is poorly understood. The gut microbiota has been shown to be important in the development of a healthy immune system, and changes in the gut microbiota are associated with inflammation. The fellowship, therefore, aims to investigate the relationship between immune responses, host genotype and gut microbiome profile that may contribute to the clinical manifestations in patients with Behçet’s disease (BD).
The key goals are:
- In vivo study: Characterising the profile of the gut microbiome using 16S rRNA (V4) amplicon sequencing of faecal samples from patients with BD and compare this to age-and gender-matched healthy and disease controls.
- In vitro study: Determining the effects of the gut microbiome and HLA-genotype on the immune responses in BD. To determine the immunostimulatory effects of BD gut microbiota, Dr Low will compare the changes in peripheral blood mononuclear cell (PBMC) surface antigen expression and cytokine production of PBMCs isolated from healthy volunteers when stimulated by faecal samples from patients with BD and healthy controls respectively. To determine whether these effects are influenced by human genetic variation, she will compare the immune responses of PBMCs isolated from HLA-B51+, HLA-B51- BD patients, HLA-B51+ and HLA-B51- healthy volunteers respectively when stimulated by BD gut microbiota.