Antibiotics ameliorate lupus-like symptoms in mice

Abstract

Gut microbiota and the immune system interact to maintain tissue homeostasis, but whether this interaction is involved in the pathogenesis of systemic lupus erythematosus (SLE) is unclear. Here we report that oral antibiotics given during active disease removed harmful bacteria from the gut microbiota and attenuated SLE-like disease in lupus-prone mice. Using MRL/lpr mice, we showed that antibiotics given after disease onset ameliorated systemic autoimmunity and kidney histopathology. They decreased IL-17-producing cells and increased the level of circulating IL-10. In addition, antibiotics removed Lachnospiraceae and increased the relative abundance of Lactobacillus spp., two groups of bacteria previously shown to be associated with deteriorated or improved symptoms in MRL/lpr mice, respectively. Moreover, we showed that the attenuated disease phenotype could be recapitulated with a single antibiotic vancomycin, which reshaped the gut microbiota and changed microbial functional pathways in a time-dependent manner. Furthermore, vancomycin treatment increased the barrier function of the intestinal epithelium, thus preventing the translocation of lipopolysaccharide, a cell wall component of Gram-negative Proteobacteria and known inducer of lupus in mice, into the circulation. These results suggest that mixed antibiotics or a single antibiotic vancomycin ameliorate SLE-like disease in MRL/lpr mice by changing the composition of gut microbiota.

A Diet-Sensitive Commensal Lactobacillus Strain Mediates TLR7-Dependent Systemic Autoimmunity

“…were associated with more severe disease whereas they were reduced as disease is controlled with dexamethasone (Luo et al, 2017). The microbiota of MRL/lpr mice, on the other hand, were described to be depleted of Lactobacillaceae and a mix of Lactobacillus strains improved outcomes in this lupus model (Mu et al, 2017b, 2017a; Zhang et al, 2014). These studies did not include gnotobiotic experiments or define which strain mediates the observed effects, making a causal relationship difficult to establish.…”

The microbiome in autoimmune diseases

“…Mu et al . showed that the administration of oral antibiotics in lupus‐prone MRL/lpr mice improve the disease by decreasing inflammatory cytokines (i.e. IL‐17) and increasing IL‐10, a cytokine with anti‐inflammatory activity.…”

“…Despite pharmacological drugs and the use of antibiotics that produce a negative impact on gut microbiota, there is a great deal of evidence that autoimmune diseases can be treated with antibiotics. Mu et al [111] showed that the administration of oral antibiotics in lupusprone MRL/lpr mice improve the disease by decreasing inflammatory cytokines (i.e. IL-17) and increasing IL-10, a cytokine with anti-inflammatory activity.…”

Lactobacillus fermentum CECT5716: a novel alternative for the prevention of vascular disorders in a mouse model of systemic lupus erythematosus

“…Importantly, treatments improving lupus symptoms in lupus MRL/lpr mice restored gut colonization of Lactobacillus spp. and decreased that of Lachnospiraceae (10,11).…”

“…In addition, antibiotic treatment initiated postdisease onset, ameliorated lupus-like symptoms that significantly altered the composition of gut microbiota, and, most notably, increased the relative abundance of Lactobacillus spp. (11). Recently, Mardani et al (12) showed that the administration of the probiotics Lactobacillus delbrueckii or Lactobacillus rhamnosus to a pristane-induced SLE mouse model was able to prevent the initiation or the progression of the SLE disease.…”