Clinical Significance of Gut Microbiota Community Types for Long-term Response to Fecal Microbiota Transplantation in Patients with Psoriatic Arthritis.

Abstract

OBJECTIVE Fecal microbiota transplantation (FMT) holds promises as a beneficial supplement to methotrexate in patients with psoriatic arthritis (PsA). We therefore investigated how gut bacterial signatures in patients and donor strain engraftment associated with long-term response to FMT. METHODS This exploratory study is based on the FLORA trial cohort encompassing 31 patients with moderate-to-high PsA disease activity and four FMT donors. Out of fifteen patients receiving one single-donor FMT, thirteen were included in the per-protocol (PP) population. Stool samples were collected before and after FMT (week 4, 12, and 26). We performed shotgun metagenomics to characterize gut microbiota features. RESULTS At baseline, 17 patients (55%) had a gut microbiota community type dominated by the Bacteroides genus (B-type) while 14 (45%) had a Prevotella-driven community type (P-type). The B- and P-type patients did not differ in disease activity nor demographics, but the B-type had a significantly higher species diversity compared to the P-type (P=0.005). In the PP population, five out of seven B-type patients vs none out of six P-type patients (P=0.021) achieved a long-term clinical beneficial response at week 26. Bacterial strain richness increased significantly from baseline to week 4 and 26 in B-type (P=0.016), but not in P-type, patients. Eighteen engrafted strains persisted only in B-type recipients by week 26, including a Bacteroides clarus strain, which demonstrated a negative effect size regarding arthritis pain and the patients' global assessment of disease. CONCLUSION Recipients with a Bacteroides-dominated community structure were more likely to achieve long-term beneficial response following one FMT.