Profiling miRNA in Systemic Lupus Erythematosus Patients Adhering to a Mediterranean Diet: An Interventional Pilot Study

<b>Background/Objectives</b>: To analyze possible epigenetic changes (miRNA) in systemic lupus erythematosus (SLE) patients on a Mediterranean diet (MD) supplemented with extra virgin olive oil (EVOO). <b>Methods</b>: Fifteen SLE patients with medium/high MD adherence were randomized into an intervention group (IG) (daily supplementation of 40 mL of EVOO for 24 weeks) or to a control group (CG). miRNA profiles from blood peripheral cells were analyzed pre-/post-intervention using next-generation sequencing. Differential expression analysis was performed by DESeq2 in R to determine changes in the log2FC. Functional enrichment analysis was performed using GeneCodis 4. <b>Results</b>: EVOO supplementation resulted in changes in the expression of 16 miRNAs in the IG. Compared to the CG, two miRNAs showed upregulation (miR-451a, miR-1307-5p) while five showed downregulation (miR-193b-50, miR-134-5p, miR1287-5p, miR-124-3p, miR-654-3p). miR-124-3p, which has been proposed to be an SLE biomarker, showed the lowest relative expression after EVOO supplementation (L2FC -3.36; <i>p_unadj</i> = 0.025), whereas miR-1307-5p (L2FC 1.115 <i>p_unadj</i> = 0.02) and miR-451a (L2FC 0.77 <i>p_unadj</i> = 0.036) showed the highest relative abundance. The functional enrichment analysis showed that Th1 and Th2 cell differentiation and the complement/coagulation cascades were among the top ten most significantly enriched pathways. <b>Conclusions</b>: Our data suggest that MD supplementation with EVOO leads to changes in the profile of miRNAs in SLE patients, potentially impacting disease pathogenesis. Further research is needed to validate these preliminary findings and the mechanisms by which EVOO modifies miRNA expression in the context of this disease.