Evidence Of a Microbial Signature In The Intestinal Microbiome In Ankylosing Spondylitis.

Costello, Mary-Ellen, Ciccia, Francesco, Gardiner, Brooke, Marshall, Mhairi, Willner, Dana, Kenna, Tony, Triolo, Giovanni and Brown, Matthew A. (2013). Evidence Of a Microbial Signature In The Intestinal Microbiome In Ankylosing Spondylitis.. In: Abstract Supplement 2013 Annual Meeting. 77th Annual Meeting of the American College of Rheumatology / 48th Annual Meeting of the Association of Rheumatology Health Professionals, San Diego CA, United States, (S1066-S1067). 25-30 October 2013. doi:10.1002/art.38216


Author Costello, Mary-Ellen
Ciccia, Francesco
Gardiner, Brooke
Marshall, Mhairi
Willner, Dana
Kenna, Tony
Triolo, Giovanni
Brown, Matthew A.
Title of paper Evidence Of a Microbial Signature In The Intestinal Microbiome In Ankylosing Spondylitis.
Conference name 77th Annual Meeting of the American College of Rheumatology / 48th Annual Meeting of the Association of Rheumatology Health Professionals
Conference location San Diego CA, United States
Conference dates 25-30 October 2013
Proceedings title Abstract Supplement 2013 Annual Meeting   Check publisher's open access policy
Journal name Arthritis and Rheumatism   Check publisher's open access policy
Place of Publication Hoboken, NJ United States
Publisher John Wiley and Sons
Publication Year 2013
Year available 2013
Sub-type Published abstract
DOI 10.1002/art.38216
Open Access Status
ISSN 0004-3591
1529-0131
2326-5205
Volume 65
Issue S10
Start page S1066
End page S1067
Total pages 2
Language eng
Formatted Abstract/Summary
Background/Purpose:
Ankylosing spondylitis (AS) occurs in genetically predisposed individuals exposed to an unknown but likely ubiquitous environmental trigger. In both AS and Crohn’s disease (CD) interplay between host genetic factors and largely undefined environmental factors, most likely involving the gut microbiome, are thought to drive the disease. To date, no comprehensive characterization of intestinal microbiota in AS patients has been performed. Our objective was to characterize the intestinal microbiome of newly diagnosed TNF-antagonist naïve AS cases using next generation sequencing and to determine if the AS gut carries a distinct microbial signature. To explore the effect of host genotype on microbiome composition we also characterized the intestinal microbiome in stools of mice with knockouts of two major AS-susceptibility genes, ERAP and IL23R, in comparison with wild-type controls.

Methods:
Terminal ileal (TI) biopsies from patients with AS, CD and healthy controls (HC) and mouse faecal samples were profiled using culture-independent high-throughput next generation sequencing of the 16S rRNA gene on an Illumina MiSeq.

Results:
Our results show the TI microbial communities of AS patients differ significantly and are more diverse than the intestinal microbial communities from those with CD and HC. The AS microbial community is characterized by higher abundance of five families of bacteria, Lachnospiraceae, Veillonellaceae, Prevotellaceae, Ruminococcusaceae and Porphyromonadaceae. Increased abundances of the families Lachnospiraceae and Prevotellaceae have been strongly associated with colitis and CD. TI microbial composition was found to correlate with disease status (P=<0.001) and greater differences were observed between disease groups than within disease groups. In mice, absence of either ERAP or IL23R alone was sufficient to significantly alter the microbiome. Absence of ERAP and IL23R caused an increase a member of the Rikenellaceae family bacteria, Rikenella Alistipes spp., compared to wild type controls (P=0.001). Rikenella Alistipes spp. is an indicator species found to be driving the AS TI microbiome signature (P=0.001). In the IL23R -/- mice, there was an increase in the genus Parabacteroides (P=0.023) (Porphyromonadaceae family). No clustering of mouse stool microbiome was noted in relationship to the cage mice were raised in, confirming that these differences are driven by the mouse genotype and not local environmental effects. In our AS cohort we also see an increase the same genus of bacteria.

Conclusion:
AS case microbiomes are different from those of CD and HC, and knockout mouse studies show that AS-associated genes shape the intestinal microbiome. This is consistent with models for AS in which genetic effects lead to changes in the gut microbiome which in turn cause immunological effects which lead to AS.
Q-Index Code EX
Q-Index Status Provisional Code
Institutional Status UQ
Additional Notes DOI is for abstracts published on pages S1-S1331

Document type: Conference Paper
Collection: UQ Diamantina Institute Publications
 
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