Session Type: Abstract Submissions (ACR)
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.
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.
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.
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.
M. E. Costello,
M. A. Brown,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/evidence-of-a-microbial-signature-in-the-intestinal-microbiome-in-ankylosing-spondylitis/