Estudio de microbiota fecal revela disbiosis específica en espondiloartritis, según subtipo, actividad de la enfermedad y tratamiento

Abstract

Introduction: Variability in microbiome composition and metabolic competence affects clinical activity and inflammatory status in spondyloarthritis-SpA.

Aim: To compare the diversity and composition of the gastrointestinal microbiome of patients with SpA.

Methods: MiSeq sequencing of the V3-V4 region of the 16S ribosomal RNA gene was performed on DNA isolated from stool. Patients with concurrent SpA and IBD were excluded.  Differences were assessed for richness and diversity indices by QIIME 2™. Differences between means > 0.2% with a p-value < 0.05 were assumed significant. Institutional ethics committee endorsement.

Results: 69 individuals included, 49 with SpA (ankylosing spondylitis-AS 72.9%, psoriatic arthritis-PsA 18.8%, reactive arthritis-ReA 8.3%) 5 positive controls-dysbiosis and 15 controls-eubiosis. Conventional treatment in 42.9%, anti-IL-17 16.3% and anti-TNF 40.8%.

By subtype, statistically significant differences in favour of AS were found for the diversity indices.  AS vs PsA there was a difference in favour of AS for Clostridium clostridioforme (p=0.002), Gemmiger formicilis (p=0.009), Roseburia inulivorans (p=0.008) and Lachnospira pectinoschiza. AS vs ReA there was a difference in favour of AS for L. pectinoschiza (p=0.009), Ruminococcus callidus (p=0.006), Clostridium ruminantium (p=0.031); G. formicilis (p=0.034). Diversity and richness showed differences in patients with high activity for Simpson's and Pielou's indices. In high activity, lower enrichment of Bacteroides eggerthii (p= 0.0003), C. ruminantium (p= 0.026) and Alistipes putredinis (p= 0.035) was found. The number of ASV was higher in the anti-IL-17 vs conventional group (p=0.025) and a trend between anti-IL-17 vs anti-TNF (p=0.09). In anti-TNF there was a lower proportion for C. clostridioforme (p=0.023), G. formicilis (p=0.030) and R. callidus (p= 0.003). In anti IL-17, Alistipes indistinctus (p= 0.012) was decreased.

Conclusions: There are differences in microbial diversity for SpA subtypes. The level of disease activity is plausible to influence the composition of the faecal microbiota. Anti-TNFα treatment may influence the microbiome environment favouring restoration of the gut microbiota, while anti-IL-17 may maintain an inflammatory environment.