Abstract

Spondyloarthritis (SpA) pathophysiology remains largely unknown. While the association with genetic factors has been established for decades, the influence of gut microbiota is only an emerging direction of research. Despite the remarkable efficacy of anti-TNF-α treatments, non-responders are frequent and no predictive factors of patient outcome have been identified. Our objective was to investigate the modifications of intestinal microbiota composition in patients suffering from SpA three months after an anti-TNF-α treatment. We performed 16S rDNA sequencing of 38 stool samples from 19 spondyloarthritis patients before and three months after anti-TNF-α treatment onset. SpA activity was assessed at each time using ASDAS and BASDAI scores. Some modifications of the microbiota composition were observed after three months of anti-TNF-α treatment, but no specific taxon was modified, whatever the clinical response. We identified a particular taxonomic node before anti-TNF-α treatment that can predict the clinical response as a biomarker, with a higher proportion of Burkholderiales order in future responder patients. This study suggests a cross-influence between anti-TNF-α treatment and intestinal microbiota. If its results are confirmed on larger groups of patients, it may pave the way to the development of predictive tests suitable for clinical practices.

Highlights

  • Associated with a persistent intestinal inflammation[10]

  • Nine patients were referred by Cochin Hospital and nine by Bordeaux Hospital; 13 men and 5 women presented with axial Ankylosing Spondylitis (N = 3) or axial and peripheral Ankylosing Spondylitis (N = 15)

  • We focused on the two subgroups of patients - those strongly responding to anti-TNF-α treatment (R, Δ Ankylosing Spondylitis Disease Activity Score (ASDAS) ≥2, n = 5) and those showing no response (NR, Δ ASDAS ≤1, n = 8) and we looked for the microbiota composition at M0 that could be predictive of the treatment outcome

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Summary

Introduction

Associated with a persistent intestinal inflammation[10]. These data suggest a close physiopathological link between gut inflammation and SpA, the recent demonstration of the crucial role of the gut microbiota in IBD raising the same query in SpA11. Costello et al studied terminal ileal biopsies obtained during colonoscopy in nine ankylosing spondylitis (AS) patients and nine controls They observed an increase in Lachnospiraceae, Veillonellaceae, Prophyromonadaceae and Bacteroidaceae and a decrease in Ruminococcaceae and Rikenellaceae in patients compared with healthy control subjects[13]. Concerning SpA, Tito et al performed investigation of bacterial composition from ileal and colonic biopsies from 27 SpA patients[15] They found different microbial profiles associated with the status of inflammation in the tissue and observed positive correlation between abundance of Dialister sp. The most commonly accepted hypothesis is that, by acting on host immune cells, they down-regulate the inflammatory cascade leading to clinical symptoms[21] In this context, the aim of our study was to investigate the modification of the intestinal microbiota three months after the introduction of an anti-TNF-α treatment and to look for a relationship between the characteristics of the microbiota composition at M0 and the clinical response to treatment

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