Query: neuropsychiatric systemic lupus erythematosus gut microbiota

title: Shared gut, but distinct oral microbiota composition in primary Sjogren's syndrome and systemic lupus erythematosus.
abstract: Alterations in the microbiota composition of the gastro intestinal tract are suspected to be involved in the etiopathogenesis of two closely related systemic inflammatory autoimmune diseases: primary Sjogren's syndrome (pSS) and systemic lupus erythematosus (SLE) Our objective was to assess whether alterations in gut and oral microbiota compositions are specific for pSS and SLE.  16S ribosomal RNA gene sequencing was performed on fecal samples from 39 pSS patients, 30 SLE patients and 965 individuals from the general population, as well as on buccal swab and oral washing samples from the same pSS and SLE patients. Alpha diversity, beta diversity and relative abundance of individual bacteria were used as outcome measures. Multivariate analyses were performed to test associations between individual bacteria and disease phenotype, taking age, sex, body mass index, proton pump inhibitor use and sequencing depth into account as possible confounding factors.  Fecal microbiota composition from pSS and SLE patients differed significantly from population controls, but not between pSS and SLE. pSS and SLE patients were characterized by lower bacterial richness, lower Firmicutes/Bacteroidetes ratio and higher relative abundance of Bacteroides species in fecal samples compared with population controls. Oral microbiota composition differed significantly between pSS patients and SLE patients, which could partially be explained by oral dryness in pSS patients.  pSS and SLE patients share similar alterations in gut microbiota composition, distinguishing patients from individuals in the general population, while oral microbiota composition shows disease specific differences between pSS and SLE patients.

title: Gut microbiota promote the inflammatory response in the pathogenesis of systemic lupus erythematosus
abstract: ObjectivesSystemic lupus erythematosus (SLE) is a chronic autoimmune disease whose onset and progression are affected by genetic and environmental factors. The purpose of this study is to identify the influence of gut microbiota in the pathogenesis of SLE, and to investigate the mechanism involved.MethodsFecal microbiota from C57/BL6 mice and SLE prone mice were examined using next generation sequencing (NGS) Germ free mice were given fecal microbiota transplantation (FMT) and their gut microbiome and gene expression in recipients' colons were examined by NGS. The anti double stranded DNA (anti dsDNA) antibodies in recipients were determined using an enzyme linked immunosorbent assay (ELISA) The immune cell profiles of mice were analyzed by flow cytometry at the 3rd week after FMT, and the expression of genes associated with SLE after FMT was determined using quantitative real time PCR (qRT PCR).ResultsThe fecal microbiota of SLE mice had lower community richness and diversity than healthy mice. Fecal microbiota of recipient mice were similar to their donors. Fecal microbiome from SLE mice could lead to a significant increase of anti dsDNA antibodies and promote the immune response in recipient mice. Our results also indicated that fecal microbiome from SLE mice resulted in significant changes in the distribution of immune cells and upregulated expression of certain lupus susceptibility genes.ConclusionsSLE is associated with alterations of gut microbiota. Fecal microbiome from SLE mice can induce the production of anti dsDNA antibodies in germ free mice and stimulate the inflammatory response, and alter the expression of SLE susceptibility genes in these mice.

title: Alteration in gut microbiota is associated with dysregulation of cytokines and glucocorticoid therapy in systemic lupus erythematosus
abstract: A growing corpus of evidence implicates the involvement of the commensal microbiota and immune cytokines in the initiation and progression of systemic lupus erythematosus (SLE) Glucocorticoids have been widely used in the treatment of SLE patients, however, glucocorticoid treatment carries a higher risk of other diseases. Using the 16S rRNA technique, we investigated the differences between the gut microbiota associated with the immune cytokines of SLE and relevant glucocorticoid treatment in a female cohort of 20 healthy control subjects (HC) 17 subjects with SLE (SLE G) and 20 SLE patients having undergone glucocorticoid treatment (SLE+G) We observed that the diversity and structure of the microbial community in SLE+G patients were significantly changed compared to that of SLE G patients, whereas the gut microbial community of the SLE+G group showed a similarity with the HC group, which implicate that the shift in the gut microbiome could represent a return to homeostasis. Furthermore, the up regulations of immune cytokines in SLE G were identified as closely related to gut dysbiosis, which indicates that the overrepresented genera in SLE patients may play roles in regulating expression level of these immune cytokines. This associated analysis of gut microbiota, glucocorticoid therapy, and immune factors might provide novel and insightful clues revealing the pathogenesis of SLE patients.

title: 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 Odoribacter and Blautia and an unnamed genus in the family Rikenellaceae) and was less diverse, with increased representation of Gram negative bacteria. The Firmicutes/Bacteroidetes 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.

title: The gut microbiota: a possible factor influencing systemic lupus erythematosus
abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown cause. In recent years, with the emergence of microbiome research, changes in the gut microbiota composition have been correlated with a variety of autoimmune disorders, and several mechanisms linking these together have been suggested, including the hygiene theory, immune system activation and hormonal effects. It has therefore been suggested that gut microbiota may play a role in SLE. In this review, we summarize recent findings on the SLE related microbiota compositions in both humans and rodents. Evidence linking microbiome with SLE opens a new avenue in researching the cause of SLE as well as improved future treatments. Recent findings Although two studies found a lower Firmicutes/Bacteroidetes ratio in SLE patients vs. controls, there were inconsistencies regarding significant differences in the abundance of specific genera or species. Studies of mouse disease models have shown some correlations between microbial compositions and disease states, also indicating differences between males and females.  Current data support an association between microbiota composition and SLE. Further research is needed to fully unravel this connection, potentially shedding light on mechanisms in SLE development and on the female bias of the disease, improving diagnosis and treatment.

title: Th17 responses and natural IgM antibodies are related to gut microbiota composition in systemic lupus erythematosus patients
abstract: Intestinal dysbiosis, characterized by a reduced Firmicutes/Bacteroidetes ratio, has been reported in systemic lupus erythematosus (SLE) patients. In this study, in vitro cultures revealed that microbiota isolated from SLE patient stool samples (SLE M) promoted lymphocyte activation and Th17 differentiation from naive CD4+ lymphocytes to a greater extent than healthy control microbiota. Enrichment of SLE M with Treg inducing bacteria showed that a mixture of two Clostridia strains significantly reduced the Th17/Th1 balance, whereas Bifidobacterium bifidum supplementation prevented CD4+ lymphocyte over activation, thus supporting a possible therapeutic benefit of probiotics containing Treg inducer strains in order to restore the Treg/Th17/Th1 imbalance present in SLE. In fact, ex vivo analyses of patient samples showed enlarged Th17 and Foxp3+ IL 17+ populations, suggesting a possible Treg Th17 trans differentiation. Moreover, analyses of fecal microbiota revealed a negative correlation between IL 17+ populations and Firmicutes in healthy controls, whereas in SLE this phylum correlated directly with serum levels of IFNg, a Th1 cytokine slightly reduced in patients. Finally, the frequency of Synergistetes, positively correlated with the Firmicutes/Bacteroidetes ratio in healthy controls, tended to be reduced in patients when anti dsDNA titers were increased and showed a strong negative correlation with IL 6 serum levels and correlated positively with protective natural IgM antibodies against phosphorylcholine.

title: 354 A comparative analysis of gut microbiota between systemic lupus erythematosus patients and non autoimmune controls: a single centrecenter cohort experience
abstract: Systemic lupus erythematosus (SLE) is the prototypical systemic autoimmune disease, and is characterised by hyperactive immune cells and antibody production. Change in gut microbiota is associated with autoimmune diseases in animal and humans models.We hypothesised that similar changes would be seen in patients with lupus, and may be future therapeutic targets.  21 patients with SLE and 12 controls with no autoimmune disease were enrolled. Stool samples obtained, homogenised and the cells lysed with 0.1 mm sterile zirconia beads and a bead beater. The DNA was extracted; V4 region of 16S rRNA gene was amplified using PCR. The purified amplicons were sequenced bi directionally. High quality reads with Phred score of =20 were obtained by using Quantitative Insights into Microbial Ecology. Chimeric sequences were identified with USEARCH and removed from analysis. Taxonomy was assigned by using a naive Bayes classifier trained with the Greengenes taxonomy.  In the SLE patients, Proteobacteria phylum was up regulated. The Lachnospiraceae family was not significantly different based on 16S rRNA sequencing. It was however significantly up regulated on quantitative PCR analysis. The genera of Blautia, Dorea and, Ruminococcus in the Lachnospiraceae family were also significantly up regulated in the lupus. The bacterial family of Erysipelotrichaceae was also significantly up regulated. Rikenellaceae, Odoribacteraceae, Christensenellaceae and Peptococcaceae families were all significantly down regulated in Lupus.  There were significant changes in gut microbiota between SLE and the control patients. The findings are similar to those reported in animal and human models with lupus and other autoimmune diseases.

title: Blood brain barrier disruption and neuroinflammation as pathophysiological mechanisms of the diffuse manifestations of neuropsychiatric systemic lupus erythematosus.
abstract: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease that can involve nervous system commitment known as neuropsychiatric systemic lupus erythematosus (NPSLE) The diagnostic of NPSLE is complex because the symptoms range from focal symptoms (e.g. strokes, thrombotic events) to diffuse disorders affecting cognition, mood and level of consciousness (e.g. acute confusional state, psychosis) Both type of manifestations of NPSLE differ in their pathological mechanisms. The focus of this review will be on the mechanisms that lead to the blood brain barrier (BBB) disruption and to the neuroinflammation related with the diffuse manifestations of NPSLE.

title: Cerebral blood flow abnormalities in neuropsychiatric systemic lupus erythematosus
abstract: To investigate the clinical characteristics, imaging changes and early diagnostic methods of neuropsychiatric systemic lupus erythematosus (NPSLE)  Thirty five SLE patients, of which 16 had overt neuropsychiatric symptoms, underwent examination for multiple autoantibodies, including anti double stranded DNA (anti dsDNA) antibody, anti nucleosome antibody, anti cardiac phospholipid antibody (aCL) IgG, aCL IgM, anti b2 glycoprotein I antibody and anti ribosomal P antibody, and the SLEDAI score of every patient was recorded. All patients further received neuropsychological tests, including the Mini Mental State Examination, the Self Rating Anxiety Scale and the Self Rating Depression Scale. Imaging examination using 3D arterial spin labeling was performed on 3.0 T MRI scanners. After processing the 3D arterial spin labeling image, the cerebral blood flow map was obtained and the cerebral blood flow value was calculated.  The values of anti dsDNA, anti nucleosome antibody, aCL IgG and anti b2 glycoprotein I antibodies were significantly higher in the NPSLE group than those in the SLE group. The SLEDAI scores of the NPSLE group were significantly higher than those of the SLE group. There were no significant differences between the NPSLE group and the SLE group in the directional ability, memory, attention, numeracy, recall ability or language ability scores on the Mini Mental State Examination scale. Furthermore, there were no symptoms of anxiety or depression in any of the patients, according to the Self Rating Anxiety Scale and Self Rating Depression Scale. In the 35 patients with SLE, decreases in blood perfusion were seen in some areas, and were unilateral and asymmetrically distributed. There was obvious asymmetry between sides in areas including the frontal lobe, temporal lobe, parietal lobe and occipital lobe. The incidence of perfusion decreases in frontal lobe in the NPSLE group was significantly higher than in the SLE group.  Neurological lesions in SLE patients can be detected by arterial spin labeling. Cerebral blood flow abnormalities may be helpful for the early diagnosis of neurological lesions in NPSLE.

title: Utility of osteopontin in cerebrospinal fluid as a diagnostic marker for neuropsychiatric systemic lupus erythematosus
abstract: The whole protein of osteopontin (OPN full) and its cleaved form (OPN N half) are involved in the immune response and the migration of immune cells to an inflammatory lesion. We have reported that serum OPN full and urine OPN N half are elevated in lupus nephritis (LN) Neuropsychiatric systemic lupus erythematosus (NPSLE) is a refractory complication of SLE. To investigate whether OPN full and OPN N half could serve as diagnostic markers for NPSLE, and to elucidate their role in NPSLE pathogenesis, the concentrations of OPN full and OPN N half in cerebrospinal fluid (CSF) were measured in NPSLE and non NPSLE patients. We found that the concentration of OPN full in the CSF was significantly higher in NPSLE than in non NPSLE, and it decreased after treatment. When the cutoff value of OPN full in CSF was set to 963.4 ng/ml, the sensitivity and specificity for the diagnosis of NPSLE were 70% and 100% respectively. The correlation analysis of OPN full, OPN N half and various cytokines/chemokines suggested that the cytokines/chemokines could be divided into two clusters: cluster A, which contains OPN full and cluster B, which contains interleukin 6. OPN full in CSF could be a novel diagnostic marker for NPSLE.