Microbiota Composition May Predict Anti-Tnf Alpha Response in Spondyloarthritis Patients: an Exploratory Study

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.

Shotgun metagenomics reveals an enrichment of potentially cross-reactive bacterial epitopes in ankylosing spondylitis patients, as well as the effects of TNFi therapy and the host’s genotype upon microbiome composition

“…Previous study of RA patients before and after synthetic disease-modifying anti-rheumatic drug treatment revealed moderate differences in the gut microbiota composition, with the perturbed microbial composition being party restored following treatment 72 . Similarly, analysis of spondylarthrosis patients before and after TNFi therapy also revealed modest differences in microbial composition yet no specific taxon was found to be modulated, likely due to sample size 73 . Utilising a larger sample size, we confirmed that TNFi therapy was correlated with a restoration of the perturbed microbial composition, and additionally identified several notable bacterial species modulated by treatment.…”

“…There has also been suggestive evidence reported that the gut microbiome is associated with differences in AS disease activity 17 . In addition, one study compared SpA patients’ stool samples before and three months after TNF-inhibitor (TNFi) treatment onset 18 . Although modest changes were found in microbiome alpha-diversity measures after TNFi treatment, no changes in specific bacterial taxa were observed.…”

Interleukin‐17 Inhibition in Spondyloarthritis Is Associated With Subclinical Gut Microbiome Perturbations and a Distinctive Interleukin‐25–Driven Intestinal Inflammation

“…In axial SpA, patients who improved with TNFi had a stable microbiome, which was less prone to perturbations with treatment. Additionally, patients who responded to TNFi tended to have higher taxa diversity prior to treatment .…”

Emerging Insights on the Interaction Between Anticancer and Immunosuppressant Drugs and Intestinal Microbiota in Pediatric Patients

“…Before anti‐TNF administration, a higher proportion of Burkholderiales (Proteobacteria) in future responder patients was identified by this study. This suggests an interaction between anti‐TNF treatment and intestinal microbiota even if further studies are needed …”

“…This suggests an interaction between anti-TNF treatment and intestinal microbiota even if further studies are needed. 94 A recent study, also performed in adult patients with rheumatoid arthritis, enrolled 42 patients divided according to current therapy: 11 patients were naïve to immunosuppressants, 11 patients were receiving methotrexate, 10 patients were receiving the anti-TNF agent etanercept, and 10 patients were receiving etancercept plus methotrexate. Ten healthy subjects were used as controls.…”