Gut Microbiota in Human Systemic Lupus Erythematosus and a Mouse Model of Lupus

Abstract

Gut microbiota dysbiosis has been observed in a number of autoimmune diseases. However, the role of the gut microbiota in systemic lupus erythematosus (SLE), a prototypical autoimmune disease characterized by persistent inflammation in multiple organs of the body, remains elusive. Here we report the dynamics of the gut microbiota in a murine lupus model, NZB/W F1, as well as intestinal dysbiosis in a small group of SLE patients with active disease. The composition of the gut microbiota changed markedly before and after the onset of lupus disease in NZB/W F1 mice, with greater diversity and increased representation of several bacterial species as lupus progressed from the predisease stage to the diseased stage. However, we did not control for age and the cage effect. Using dexamethasone as an intervention to treat SLE-like signs, we also found that a greater abundance of a group of lactobacilli (for which a species assignment could not be made) in the gut microbiota might be correlated with more severe disease in NZB/W F1 mice. Results of the human study suggest that, compared to control subjects without immune-mediated diseases, SLE patients with active lupus disease possessed an altered gut microbiota that differed in several particular bacterial species (within the genera and and an unnamed genus in the family ) and was less diverse, with increased representation of Gram-negative bacteria. The/ ratios did not differ between the SLE microbiota and the non-SLE microbiota in our human cohort. SLE is a complex autoimmune disease with no known cure. Dysbiosis of the gut microbiota has been reported for both mice and humans with SLE. In this emerging field, however, more studies are required to delineate the roles of the gut microbiota in different lupus-prone mouse models and people with diverse manifestations of SLE. Here, we report changes in the gut microbiota in NZB/W F1 lupus-prone mice and a group of SLE patients with active disease.

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

“…Our results in gut microbiota composition are consistent with the relative higher abundance of a group of Lactobacilli found in the gut microbiota of NZBWF1 mice associated with deteriorated disease (8). However, these authors did not compare the fecal microbiota between NZBWF1 mice and a control mouse strain.…”

“…Gut microbiota might trigger symptoms and progression of some autoimmune diseases (6). A disbalance in gut microbiota populations in SLE patients was described, characterized by a significantly lower Firmicutes/ Bacteroidetes (F/B) ratio (6,7), a lower diversity of gut microbiota, and changes in several bacterial species, in particular, an increased representation of Gram-negative bacteria consistent with an increased serum level of LPS (8). In lupus-prone Murphy Roths Large (MLR)/Mp-Faslpr (lpr) mice, it has been described that the dynamics of microbiota play a critical role in lupus pathogenesis (9).…”

“…In these female mice, endothelial dysfunction occurs before high blood pressure (BP), which is not dependent on glomerulonephritis (15). Recent studies showed that the composition of gut microbiota changed markedly from before to after the onset of lupus disease in these SLE mice (8). Moreover, Lactobacillus paracasei GMNL-32, L. reuteri GMNL-89, and L. reuteri GMNL-263 significantly increased serum antioxidant activity in NZB/W F1 mice, reduced proinflammatory cytokine levels, and attenuated hepatic TLR (4,5,7,9) and MyD88 signaling, which suggests that these specific Lactobacillus strains can be used as part of a comprehensive treatment of SLE patients (18).…”

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

“…In this study, Lactobacillus spp. 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).…”

Metabolic determinants of lupus pathogenesis

“…142 Fecal metabolomics may be important considering increasing reports of altered SLE fecal microbiomes both in patients and murine models of lupus. [143][144][145][146][147][148][149] Pathway analyses of serum metabolite profiles also suggested an altered gut microbial metabolism in SLE patients compared to HCs, 135,150 including an increase in total free fatty acids (FFAs) and short-chain fatty acids (SCFAs) synthesized by bacteria. 146 Additionally, disrupted metabolic pathways were found in the urine of SLE patients compared to HCs including amino acid, TCA cycle, and purine/pyrimidine metabolism.…”