mattbrownkclacuk Treating axial spondyloarthritis via the gut microbiome What evidence is there for a role of diet and the gut in arthritis Human migration studies Genetics Gut microbiome profiling studies ID: 935144
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Matt Brown, Director, GSTT and KCL NIHR BRC
matt.brown@kcl.ac.uk
Treating axial spondyloarthritis via the gut microbiome
Slide2What evidence is there for a role of diet and the gut in arthritis
Human migration studies
Genetics
Gut microbiome profiling studies
Animal studies
Therapeutic trials
Slide3Gut Infections and SpondyloarthritisBacterial dysentery is a common trigger of reactive arthritis
AS and inflammatory bowel disease commonly occur togetherIBD is thought to be caused by bacteria driving inflammation in the wall of the intestineInflammation in the small intestine is common in AS, and correlates with disease activity.In B27-transgenic rat modelRemains disease free in germ-free environmentArthritis in this model can be prevented using Lactobacillus rhamnosus
as a probiotic.
Slide4AS and RA are rare in West Africa despite some ethnic groups having at least moderate HLA-B27 and HLA-DR4 frequencies.
The descendants of these West Africans living in the United States have much higher incidences of these diseases.
Urbanised Black Africans also have higher prevalences of these diseases.
Migration studies confirm AS risk is environmentally determined
Slide5Li et al, Genes
Immun, 2017Genetic studies show that many of the genes driving AS operate in the gut
Slide6Thomas, Ruutu. Arthritis Rheum, 2012.
Slide7The bacteria found in the gut of AS patients are different from those found in unaffected people
Using 16S sequencing on terminal
ileal biopsies, AS cases can be distinguished based on the microbial profile from healthy controls.
AS cases have higher abundances of Lachnospiraceae (P=0.001),Ruminococcaceae (P=0.012)Rikenellaceae (P=0.004)
Porphyromonadaceae (P=0.001)Bacteroidaceae (P=0.001)Decreases were noted in:
Veillonellaceae (P=0.01)Prevotellaceae (P=0.004)Costello et al., Arthritis Rheumatol, 2014
Slide8Slide9In the absence of disease, HLA-B27 influences the bacteria found in the gut
Permanova = 0.04All samples Stool
Permanova
= 2x10
-4
Asquith et al, Arthritis Rheum, 2019.
Slide10Successful treatment of AS normalises stool microbiome
Yin et al, Ann Rheum Dis, 2019.
Slide11Leaky Gut allows bacteria into the body
Slide12Bacteria are seen invading the gut mucosa in AS patients (A-C) but not healthy controls (D).
The extent of bacterial invasion correlates with the number of inflammatory cells in the gut mucosa (E)
This is associated with higher serum LPS levels in AS patients.
Slide13Gut bacteria produce toxins or fewer protective compounds
Slide14Untreated AS patients carry fewer ‘protective’ bacteria
Yin et al, Ann Rheum Dis, 2019.
Slide15Gut bacteria trick immune system by looking like parts of body
Slide16AS patients T-cells are reacting to gut bacteria
HLA-B27 operates to present foreign ‘antigens’ to part of the immune system called ‘CD8 T-cells’
Everyone has ~1 billion different T-cells in their body.
We found a specific T-cell type that was present in 18/37 (49%) AS patients but only 2/19 HLA-B27 healthy people.This T-cell type had been identified before…
In a patient with reactive arthritis caused by bacterial dysentery…
Slide17Slide18Treatment Options
Slide19Slide20Slide21Clinical Trial of FMT in
AxSpA
Slide22Clinical Trial of FMT in
AxSpA
Slide23Research Team