Background/Purpose: Nearly 8% of patients with spondyloarthritis (SpA) manifest symptoms that are compatible with active inflammatory bowel disease (IBD), despite not having any previous diagnosis of chronic intestinal pathologies. It is well established that the microbiome plays an important role in immunity, and there is growing evidence showing that intestinal dysbiosis of microbial communities is associated with different immune-mediated diseases. This association is particularly notable in IBD, which is characterized by aberrant microbiome communities and can also be treated by restoring homeostasis through fecal microbiota transplants. We therefore hypothesize that the gut microbiome could be a determining factor in the etiology of psoriatic arthritis (PsA), a type of SpA, and a potential modulator of co-occurrence with intestinal inflammation.

Methods: As part of the EISER study, we selected a subset of 196 subjects diagnosed with with axial, periferic or mixed forms of PsA, who had no prior diagnosis of IBD or other chronic intestinal pathologies. The presence of subclinical and clinical IBD was evaluated at time of enrollment. Subjects with fecal calprotectin (CP) levels less than 80µg/g of fecal matter were considered negative for IBD. For patients with CP levels of 80 µg/g or higher, IBD was diagnosed based on colonoscopy and histological analysis of biopsies collected during the procedure. Capsule endoscopy was performed on those patients with a negative colonoscopy result for additional confirmation. Stool samples were collected from all participants, and microbial DNA was extracted for shotgun metagenomic sequencing using the Illumina HiSeq platform. Sequenced data was processed using MetaPhlAn 4 to estimate microbial composition and HUMAnN 2 to annotate bacterial pathways.

Results: Twenty-five out of 196 subjects in our cohort (12.75%) had subclinical IBD (sIBD), two of whom (1.02% of total) were confirmed to have clinical IBD (cIBD). The use of proton-pump inhibitors (PPI) resulted in significant differences in overall beta diversity (PERMANOVA, p < 0.008). The levels of fecal CP were significantly correlated with the abundance of multiple species within the Streptococcus genus and with Rothia mucilaginosa. Patients with sIBD had lower abundance of Dialister,Barnesiella spp and Eubacterium rectale, and higher abundance of taxa including Blautia spp, Prevotella copri and Roseburia compared with non sIBD patients. These findings were further confirmed in the two cIBD patients.

Conclusion: Microbiome composition was impacted by the use of PPIs, in agreement with previous reports. Bacteria typically found in the oral cavity were significantly correlated with CP levels, suggesting a potential role for oral taxa in pro-inflammatory responses in PsA patients. We identified taxa differentially enriched in sIBD patients consistent with patterns observed in the two patients with confirmed IBD diagnosis, suggesting a potential role for these taxa as biomarkers. Further analysis will evaluate differences in microbial pathways associated with disease groups and medications, as well as the relation between gut microbiome composition, function and blood proteomic biomarkers.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-eiser-study-identifying-microbial-factors-associated-with-subclinical-gut-inflammation-in-spondyloarthritis-patients/