An increasing number of studies have provided strong evidence that gut microbiota interact with the immune system and stimulate various mechanisms involved in the pathogenesis of auto-immune diseases such as Systemic Lupus Erythematosus (SLE). Indeed, gut microbiota could be a source of diagnostic and prognostic biomarkers but also hold the promise to discover novel therapeutic strategies. Thus far, specific SLE microbial signatures have not yet been clearly identified with alteration patterns that may vary between human and animal studies. In this study, a comparative analysis of a clinically well-characterized cohort of adult patients with SLE showed reduced biodiversity, a lower Firmicutes/Bacteroidetes (F/B) ratio, and six differentially abundant taxa compared with healthy controls. An unsupervised clustering of patients with SLE patients identified a subgroup of patients with a stronger alteration of their gut microbiota. Interestingly, this clustering was strongly correlated with the disease activity assessed with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score (p = 0.03, odd ratio = 15) and the identification of specific alterations involving the F/B ratio and some different taxa. Then, the gut microbiota of pristane-induced lupus and control mice were analyzed for comparison with our human data. Among the six differentially abundant taxa of the human disease signature, five were common with our murine model. Finally, an exhaustive cross-species comparison between our data and previous human and murine SLE studies revealed a core-set of gut microbiome species that might constitute biomarker panels relevant for future validation studies.

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease driven by complex interactions between genetics and environmental factors. SLE is characterised by breaking self-immune tolerance and autoantibody production that triggers inflammation and damage of multiple organs. Given the highly heterogeneous nature of SLE, the treatments currently used are still not satisfactory with considerable side effects, and the development of new therapies is a major health issue for better patient management. In this context, mouse models significantly contribute to our knowledge of the pathogenesis of SLE and are an invaluable tool for testing novel therapeutic targets. Here, we discuss the role of the most used SLE mouse models and their contribution to therapeutic improvement. Considering the complexity of developing targeted therapies for SLE, adjuvant therapies are also increasingly proposed. Indeed, murine and human studies have recently revealed that gut microbiota is a potential target and holds great promises for successful new SLE therapies. However, the mechanisms of gut microbiota dysbiosis in SLE remain unclear to date. In this review, we propose an inventory of existing studies investigating the relationship between gut microbiota dysbiosis and SLE to establish microbiome signature that may serve as a potential biomarker of the disease and its severity as well as a new potential therapy target. This approach may open new possibilities for early diagnosis, prevention and therapeutic perspectives of SLE based on gut microbiome.