Gut Microbiome and Metabolites in Systemic Lupus Erythematosus: Link, Mechanisms and Intervention

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.

Gut Microbiota Dysbiosis in Systemic Lupus Erythematosus: Novel Insights into Mechanisms and Promising Therapeutic Strategies

“…Previous studies have shown that HSD could activate DCs and induce the production of pathogenic T Helper 17 (Th17) cells through the p38/MAPK-STAT1 signaling pathway, resulting in gut microbiota dysbiosis, hypertension and autoimmune progression (37)(38)(39). Moreover, gut microbiota dysbiosis may induced immune system imbalance and aggravates SLE (40). There are other potential mechanisms underlying for the role of gut microbiota dysbiosis in SLE, which we will elaborate on the following aspects.…”

“…At present, the study of intestinal bacteria intervention in the treatment of SLE is still in its infancy, but it can learn from other dysbacteriosis-associated diseases and predict future regimens in the treatment of SLE. As described in a recent review ( 40 ), probiotics/prebiotic therapy are currently practical approaches for ameliorating intestinal dysbacteriosis to treat SLE. Probiotics and prebiotics can induce differentiation of Treg cells, improve Th17/Th1 imbalance, and reduce the production of autoantibodies, thereby reducing the severity of lupus ( 40 ).…”

“…As described in a recent review ( 40 ), probiotics/prebiotic therapy are currently practical approaches for ameliorating intestinal dysbacteriosis to treat SLE. Probiotics and prebiotics can induce differentiation of Treg cells, improve Th17/Th1 imbalance, and reduce the production of autoantibodies, thereby reducing the severity of lupus ( 40 ). Nevertheless, the efficacy of probiotics/prebiotic in the treatment of SLE remains unclear and has not been confirmed by clinical trials.…”

Microbiota-Derived Propionate Modulates Megakaryopoiesis and Platelet Function

“…Last, as for pSS the involvement of the gut microbiota along with SCFAs was well reviewed by Zhang et al. ( 42 ) this further suggested the general potential benefit of C3 supplementation on autoimmune diseases via modulation of megakaryocytes. A direct role of megakaryocytes in the susceptibility of arthritis was shown by a study on IgG-mediated arthritis in different mouse models of kit-insufficiency.…”

Human Microbiome in Children, at the Crossroad of Social Determinants of Health and Personalized Medicine

“…The diagnostic and therapeutic potential of SCAs is being explored in different settings, from allergies to autoimmune disorders such as systemic lupus erythematosus [ 48 ]. In addition, SCFAs and other microbiota-derived metabolites such as lipopolysaccharides, beta-cresol, and bacterial toxins in blood and urine are being explored as diagnostic tools and for early intervention in autism spectrum disorder [ 49 ].…”