Disturbed gut virome with potent interferonogenic property in systemic lupus erythematosus

Abstract

Accumulating evidence suggests an essential role of disturbed gut microbiota in the etiopathogenesis of systemic lupus erythematosus (SLE), but it remains unclear as to gut virome. In this study, fecal virus-like particles (VLPs) isolated from 76 non-treated SLE patients and 75 healthy controls were subjected to gut virome profiling. The proportion of bacteriophages was significantly elevated in the SLE gut, and the altered viral taxa were correlated with clinical parameters. Gut virome and bacteriome were closely associated with each other in SLE patients. The combination of gut viral and bacterial markers displayed better performance in distinguishing SLE patients from healthy controls. Further, VLPs from non-treated SLE patients promoted interferon-α production in an epithelial cell line and human immune cells. Intriguingly, the interferon-stimulatory capacity diminished in VLPs from post-treated SLE patients. Our findings may shed novel insights into SLE pathogenesis. Further in-depth understanding of gut virome might help develop future biomarkers and therapeutics for SLE patients.