Gut microbiota in systemic lupus erythematosus patients and lupus mouse model: a cross species comparative analysis for biomarker discovery

Abstract

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.

Longitudinal gut microbiome analyses and blooms of pathogenic strains during lupus disease flares

“…In other diseases, at most only infrequent concordance between specific host-associated micro-organisms and pathology has been reported 26. By contrast, evidence of RG expansions in patients with active SLE, and especially LN, has now been found in three US cohorts along with cross-sectional surveys of serum IgG anti-LG studies,7 a Scandinavian cohort,27 a large untreated cohort in China28 and a French cohort 29. The linkage between RG and SLE is also remarkable as RG bloom-associated disease flares occurred in individuals of diverse race and ethnicity (online supplemental table S1).…”

Microbiome dynamics in rheumatic diseases

“…Additionally, there exists a correlation between gut microbiome disruptions and the severity of SLE. Toumi et al [13 ]. Similar to RA, the researchers identified seven marker strains in the intestines of SLE patients, known to be associated with oral inflammation, hinting at the potential oral microbiome origin of the enriched bacteria in SLE patients [27].…”

“…Additionally, there exists a correlation between gut microbiome disruptions and the severity of SLE. Toumi et al [13 ▪ ] conducted an unsupervised clustering analysis of intestinal microbiota composition in SLE patients and identified two main clusters. Cluster 2 was enriched in patients with active SLE, characterized by significantly higher SLEDAI scores [13 ▪ ].…”

“…Toumi et al [13 ▪ ] conducted an unsupervised clustering analysis of intestinal microbiota composition in SLE patients and identified two main clusters. Cluster 2 was enriched in patients with active SLE, characterized by significantly higher SLEDAI scores [13 ▪ ]. Similar to RA, the researchers identified seven marker strains in the intestines of SLE patients, known to be associated with oral inflammation, hinting at the potential oral microbiome origin of the enriched bacteria in SLE patients [27].…”

Progress on the regulation of intestinal flora in rheumatic immune diseases

“…Recent data shows that the global prevalence of SLE is increasing during these years. Analysis of US Medicare data indicates that the age-and sex-adjusted prevalence of SLE was 0.301% in 2009 and rose to 0.367% by 2016 (REF 9) [4]. SLE would cause organic brain syndrome and may seriously affect patients' fertility.…”