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Abstract
Systemic lupus erythematosus (SLE), often considered the prototype of autoimmune diseases, is characterized by over-activation of the autoimmune system with abnormal functions of innate and adaptive immune cells and the production of a large number of autoantibodies against nuclear components. Given the highly complex and heterogeneous nature of SLE, the pathogenesis of this disease remains incompletely understood and is presumed to involve both genetic and environmental factors. Currently, disturbance of the gut microbiota has emerged as a novel player involved in the pathogenesis of SLE. With in-depth research, the understanding of the intestinal bacteria-host interaction in SLE is much more comprehensive. Recent years have also seen an increase in metabolomics studies in SLE with the attempt to identify potential biomarkers for diagnosis or disease activity monitoring. An intricate relationship between gut microbiome changes and metabolic alterations could help explain the mechanisms by which gut bacteria play roles in the pathogenesis of SLE. Here, we review the role of microbiota dysbiosis in the aetiology of SLE and how intestinal microbiota interact with the host metabolism axis. A proposed treatment strategy for SLE based on gut microbiome (GM) regulation is also discussed in this review. Increasing our understanding of gut microbiota and their function in lupus will provide us with novel opportunities to develop effective and precise diagnostic strategies and to explore potential microbiota-based treatments for patients with lupus.
Highlights
Systemic lupus erythematosus (SLE) is one of the most common systematic autoimmune diseases
When 5, 10 or 30% of SLE gut microbiota were replaced with the same proportions of Bifidobacterium bifidum LMG13195 (Bb) or a mixture of two Clostridia strains (CI: Ruminococcus obeum DSM25238 and Blautia coccoides DSM935), which are known for Treg-inducing effects, Bb and CI significantly reduced CD4+ lymphocyte over-activation and Th17/Th1 balance, respectively [124]
Some recent studies have identified several pathobionts and pathways that are related to local or systemic inflammation processes and immune system dysregulation in animal lupus models (Table 2), it remains to be determined how consistent they are among different patient populations and which microbial antigens drive immune intolerance to produce several lupus-related autoantibodies
Summary
Systemic lupus erythematosus (SLE) is one of the most common systematic autoimmune diseases. It predominantly affects women of childbearing age and targets a diverse array of organs, including the skin, joints, kidney, lung, heart, and gastrointestinal tract, among others. Changing the profile of metabolites is another important way in which gut bacteria affect host immune homeostasis. We aim to compile the available advances in understanding how gut microbiota functionally affect the development of various autoantibodies and how bacteria-derived metabolites contribute to inflammation and the interaction between intestinal microbiota and medication in the pathogenesis of SLE. We present evidence- or hypothesis-based perspectives for new therapeutic strategies for SLE
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