Disease ⇒ Systemic lupus erythematosus {40000134} Record Keys Type:Disease Parent:[ ] Definition:Systemic lupus erythematosus Details Initialisation date:2020-09-13 Other Terms:SLE , Lupus LinksWickipediaMerck Manual Meta Information MedDra ID:10042945 MedDra Level:pt ICD:[ ] Category:Rheumatology, Immunology Zone:[ ] Mechanism:[ ] Notes: - Mice with lupus had decreased amounts of Lactobacillus. - The lupus mice had a "leaky gut" a condition that affects the intestinal lining. - Addition of Lactobacillus to the diet only affected female mice and not males. (1) - Women diagnosed with SLE had roughly five times more gut bacteria known as Ruminococcus gnavus. - New treatments could also be used to promote growth of Bacteroides uniformis, bacteria thought to hinder growth of R. gnavus in the gut and whose numbers decreased by as much as fourfold in study participants with lupus when compared to those without the disease. - Women diagnosed with SLE had roughly five times more gut bacteria known as Ruminococcus gnavus, than 17 women of similar ages and racial backgrounds who did not have the disease and were healthy. - Disease "flares," which can range from instances of skin rash and joint pain to severe kidney dysfunction requiring dialysis, closely tracked major increases in R. gnavus bacterial growth in the gut, alongside the presence in blood samples of immune proteins called antibodies, specifically shaped to attach to the bacteria. Study participants with kidney flares had especially high levels of antibodies to R. gnavus. - Strong immune antibody reactions to R. gnavus in the blood because the gut lining prevents the bacterium from escaping to other parts of the body. Researchers say this suggests that small pieces of the bacteria, known as antigens, must have "leaked" into the gut to trigger the immune reaction. (3) Shared Reference Notes [1.1] - Many Lupus patients have little or no detectable perturbations in representation of the #Lachnospiraceae family or abundance of #Ruminococcus gnavus species overtime. - Vancomycin-treated mice showed an increase in #Lactobacillus animalis in the gut, whereas there was a depletion in the total gut bacterial load. - Oral administration of L. animalis led to an exacerbation of lupus postpartum consisting of worsened splenomegaly and proteinuria while this did not affect the course of the disease in mice that were not pregnant or lactating. - L. animalis acted by inhibiting the serum enzyme indoleamine 2,3-dioxygenase alongside a differential production of immunosuppressive and pro-inflammatory mediators in the postpartum period. - The enriched L. animalis was involved in the vancomycin-driven effects on decreased T regulatory cells and increased pro-inflammatory cytokines. [1.2] - Anti-RG antibodies correlated directly with SLEDAI score and antinative DNA levels, but inversely with C3 and C4. - Intestinal expansions of #Ruminococcus gnavus were directly proportional to overall disease activity and most pronounced in those with lupus nephritis. - Lupus faecal samples displayed increases in sIgA-coated #Ruminococcus gnavus bacteria. - Patients with lupus nephritis displayed elevated serum IgG predominantly to #Ruminococcus gnavus strain-restricted cell wall lipoglycan antigens. [1.3] [1.4] - Bacilli and Lactobacillales were positively correlated with the risk of SLE. - Bacillales, Coprobacter and Lachnospira were negatively correlated with SLE risk. - Bacilli, Lactobacillales, and Eggerthella were risk factors for SLE. - Bacillales and Coprobacter served as protective factors for SLE. - Ruminiclostridium was negatively associated with SLE. - Actinobacteria might reduce the SLE risk. [1.5] - The SLE-enriched genera, including Bacteroides, were positively correlated with several SLE-enriched metabolites, including #Olopatadine. - The SLE-depleted genera, such as Pseudomonas, were negatively correlated to SLE-depleted cytokines, including interleukin-8. - Megamonas and Phocaeicola were negatively correlated with serum complement component 3, and Streptococcus was positively correlated with IgG. - #Olopatadine, were more abundant in SLE patients. #Olopatadine appears to have significant anti-inflammatory activity, and inhibits histamine release from mast cells. Thus, the increase of #Olopatadine in urine might play a potential protective role for SLE patients. [1.6] - after #Staphylococcus aureus was epicutaneously applied on NfkbizΔK5 mice, NfkbizΔK5 mice developed SLE-associated autoantibodies, anti-dsDNA antibodies, anti-Sm antibodies, and glomerulonephritis with IgG deposition. - This staphylococcal skin colonization promoted caspase-mediated keratinocyte apoptosis and neutrophil activation, inducing the interleukin-23 (IL-23)/IL-17 immune response by activating dendritic cells and T cells. - the subcutaneous administration of anti–IL-23p19 and anti–IL-17A antibodies alleviated the systemic autoimmune response. [1.7] [#Colorectal cancer, #Crohn’s disease] [#Bacteriophage, #Western-style diet] - the abundance of a class of crAss-like phages, a group of related viruses that includes some of the most abundant viruses of the human gut, were higher in populations with non-westernized dietary habits - several types of crAss-like phages were present at decreased levels in people with #Rheumatoid Arthritis, systemic lupus erythematosus, #Ulcerative Colitis and Crohn disease, and at increased levels in people with colon cancer. [1.8] - Acidic Water associated with #Turicibacter spp., which is frequently found in active lupus disease, and all-trans #Retinoic acid in #Bacteroidetes associated with renal pathology. [#Flavonoid, #Polyphenols] - dietary polyphenol as dihydrochalcones and flavanones affected the gut microbiome and ameliorated lupus disease activity. - dietary flavones increased #Blautia (family: Lachnospiraceae), and that often found in active lupus diseases. - in Mice > #Resistant Starch (RS), #Retinoic acid (RA) or all-trans #Retinoic acid (tRA), and acidic water (AW) had influenced the gut microbiome, leading to an improved lupus development. [1.9] [#Ruminococcus gnavus] - Expansions of only the anaerobic commensal, Ruminococcus (#Blautia) gnavus (RG) occurred at times of high-disease activity, and were detected in almost half of patients during lupus nephritis (LN) disease flares. [#Ruminococcus gnavus] - SLE > The cell membrane-associated lipoglycans share conserved structural features documented by mass spectroscopy, and highly immunogenic repetitive antigenic-determinants, recognised by high-level serum IgG2 antibodies, that spontaneously arose, concurrent with RG blooms and lupus flares. - SLE > The abundance of #Acholeplasma, #Capnocytophaga and #Leptotrichia were negatively correlated with SLEDAI score, and the abundance of #Bacteroides, #Ruminococcus and #Akkermansia had an inverse correlation with the serum levels of complement C3 - #Actinobacteria, #Bacillales, #Coprobacter and #Lachnospira were inversely correlated with the risk of SLE, and #Bacilli, Eggertella and #Lactobacillales might be the risk factors of SLE. - peptide “DGQFCM” mimicking human Fas antigen from #Akkermansia muciniphila specifically binds to the IgG produced by memory B cells from lupus patients - #Bacteroides fragilis treatment restored the Th17/Treg balance and ameliorated the lupus activity of MRL/lpr mice - Patients with SLE produce autoantibodies against Ro60 which is an evolutionarily conserved RNA binding protein, and the antibody against Ro60 is the most common and earliest preclinical anti-nuclear antibody. - bacteria expressing Ro60 orthologs was present in the skin, oral, and gut of both lupus patients and healthy controls. - colonization of germ-free mice with #Bacteroides thetaiotaomicron containing Ro60 ortholog caused T and B cell responses against human Ro60 and glomerular immune complex deposition - SLE patients displayed higher serum levels of #IL-2 and #IL-6. - The abundance of #Roseburia and #Faecalibacterium was inversely correlated with #IL-6, the abundance of #Roseburia had a negative correlation with #IL-2, and the abundance of #Bacteroides had a positive correlation with #IL-2. - SLE > the abundance of #Bacteroidetes was positively correlated with glomerular pathological scores. - #Bifidobacterium can maintain the balance of Treg/Th17/Th1 by suppressing the excessive activation of CD4+ lymphocytes in SLE patients - In SLE patients, increased fecal albumin and #Calprotectin were found in the stool sample - SLE > increased abundance of genera #Candidatus saccharimonas, #Desulfovibrio, #Odoribacter and #Roseburia in mice treated with HCMVpp65 peptide is significantly correlated with lupus-like effects including enhanced levels of creatinine, proteinuria, glomerular damage and anti-dsDNA antibodies. - increased abundance in #Enterobacteriaceae and #Enterococcaceae and decreased abundance in #Ruminococcaceae in the gut microbiota of patients with SLE. [#Enterococcus gallinarum] SLE > higher titers of anti-E. gallinarum IgG in patients were significantly correlated with the presence of anti-Ribosomal P, anti-dsDNA and anti-Sm autoantibodies. - E. gallinarum was detected in the mesenteric veins, mesenteric lymph nodes (MLN), spleen, and liver of (NZW × BXSB)F1 hybrid mice. - E. gallinarum was detected in liver biopsy samples from both lupus patients and autoimmune hepatitis patients. - Th17 cells were induced in the small intestinal lamina propria and mesenteric lymph nodes of C57BL/6 mice monocolonized with E. gallinarum. - The induction of Th17 and autoantibodies by E. gallinarum was eliminated by the administration of a selective AhR antagonist, which indicates that E. gallinarum promotes autoimmunity by AhR signaling. - the presence of E. gallinarum upregulated Enpp3, which can increase the number of plasmacytoid dendritic cells (pDCs). Both murine hepatocytes and human hepatocytes induced type I interferon under the stimulation of E. gallinarum. [#Enterococcus gallinarum] - Anti-β2GP1 antibody is also a diagnostic index for SLE. - β2GP1 ortholog expressed by E. gallinarum was found to induce anti-β2GP1 antibody - #Lactobacillaceae significantly decreased and #Lachnospiraceae significantly increased in lupus-prone MRL/lpr mice. - Increased intestinal abundance of #Lactobacillaceae was associated with improvement of lupus symptoms, while increased colonization of #Lachnospiraceae was associated with disease progression - #Lactobacillus treatment decreased #IL-6 and increased #IL-10 production in the gut contributing to an anti-inflammatory environment. - Environmental factors including ultraviolet #Light, silica exposure, cigarette smoking, viral and bacterial infections, and sex hormones are involved in the pathogenesis of SLE. [#Limosilactobacillus (Lactobacillus) reuteri] - SLE > abundance of Lactobacill. reuteri increased in TLR7.1 Tg mice and Lactobacill. reuteri colonization exacerbated systemic autoimmunity under specific-pathogen-free and gnotobiotic conditions. - β2GPI-reactive memory CD4+ memory T cell clones and APS-derived β2GPI autoantibody cross-reacted with mimotopes expressed by a gut commensal #Roseburia intestinalis. - oral gavage of (NZW x BXSB)F1 mice with #Roseburia intestinalis led to increased anti-human β2GPI IgG autoantibodies and thrombotic events. - #Ruminococcus gnavus (RG) showed a mean 5-fold overabundance in lupus patients compared with healthy controls. And patients with high disease activity and especially lupus nephritis showed the greatest expansion of RG. - anti-RG antibodies were directly correlated with anti-DNA levels and SLEDAI scores, while they were negatively correlated with C3 and C4. - Patients with active nephritis including Class III and IV exhibited the highest levels of anti-RG strain restricted antibodies in serum. - #Ruminococcus gnavus (RG) strains from lupus patients, and found that lupus-derived RG strains enhanced intestinal permeability, elevated serum levels of zonulin which is a regulator of tight junction formation between cells forming the intestinal barrier, and translocated to mesenteric lymph nodes. - The level of intestinal permeability induced by RG has a significant correlation with anti-native DNA autoantibodies and serum IgG anti RG cell-wall lipoglycan antibodies. - antigen in #Ruminococcus gnavus strain CC55_001C could cross-react with anti-dsDNA antibodies. - The genus #Streptococcus was associated with the lupus activity [1.11] [1.12] - #Lactobacillus fermentum CECT5716 or #Bifidobacterium breve CECT7263 prevented #Hypertension and endothelial dysfunction in a mouse lupus model induced by TLR-7 activation. [1.13] [#antiphospholipid syndrome] - In mice, intake of a #Ginger extract (either by oral gavage or mixed with chow) reduced NETosis in models of APS and lupus. - This was accompanied by a decrease in disease-relevant phenotypes, including thrombosis in the setting of APS and autoantibody formation in the setting of lupus [#antiphospholipid syndrome] [#Antimicrobial peptides, #Gingerols] - 6-gingerol, the most abundant bioactive phytochemical in #Ginger root, inhibited neutrophil phosphodiesterase (PDE) activity, boosting intracellular cyclic AMP (cAMP) levels and thereby counteracting neutrophil hyperactivity in mouse models of APS and lupus [1.14] [#Diabetes Type 1, #Hashimoto’s thyroiditis, #Psoriasis, #Sjögren syndrome ] Patients with psoriatic disease had a significantly higher risk of #Crohn’s disease , #Ulcerative Colitis, systemic lupus erythematosus, #Rheumatoid Arthritis, #Ankylosing spondylitis , #Alopecia areata, and type 1 diabetes. - the risk of #Graves’ disease, Hashimoto’s disease, Sjögren’s syndrome, and #Systemic sclerosis was not significantly different between the groups. [1.15] [#Rheumatoid Arthritis] - #Ruminococcus gnavus was associated with lupus nephritis, RA and #Spondyloarthritis. [1.16] - SLE patients have intestinal flora imbalance. It is characterized by a significant decrease in #Firmicutes/#Bacteroidetes ratio, a decrease in intestinal flora diversity, an increase in the number of Gram-negative bacteria, and an increase in serum #Lipopolysaccharide (LPS) [#Lactobacillus delbrueckii] - Compound probiotics (#Lactobacillus rhamnosus and Lactobacillus del brueckii) prophylactically fed SLE model mice for 2 months, the levels of related autoantibodies and the frequency of Th1 and Th17 cells in the spleen were decreased; meanwhile, the serum pro-inflammatory factors #IL-17 and IFN-γ levels decreased [1.17] - X-chromosome inactivation (XCI), the epigenetic mechanism ensuring the silencing of one X in females, the noncoding RNA Xist, in female mice. - This resulted in reactivation of genes on the inactive X, including members of the Toll-like receptor 7 (TLR7) signaling pathway, in monocyte/macrophages and dendritic and B cells > LupusReferences Notes[ ]
