scholarly journals The bladder microbiome, metabolome, cytokines, and phenotypes in patients with systemic lupus erythematosus

2022 ◽  
Author(s):  
Fengping Liu ◽  
Jingjie Du ◽  
Qixiao Zhai ◽  
Jialin Hu ◽  
Aaron W. Miller ◽  
...  

Background and aims: Emerging studies reveal a unique bacterial community in the human bladder, with alteration of composition associated to disease states. Systemic lupus erythematosus (SLE) is a complex autoimmune disease that is characterized by frequent impairment of the kidney. Here, we explored the bladder microbiome, metabolome, and cytokine profiles in SLE patients, as well as correlations between microbiome and metabolome, cytokines, and disease profiles. Methods and materials: We recruited a cohort of 50 SLE patients and 50 individually matched asymptomatic controls. We used transurethral catheterization to collect urine samples, 16S rRNA gene sequencing to profile bladder microbiomes, and LC-MS/MS to perform untargeted metabolomic profiling. Results: Compared to controls, SLE patients possessed a unique bladder microbial community and increased alpha diversity. These differences were accompanied by differences in urinary metabolomes, cytokines, and patients’ disease profiles. 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 IL-8. Alteration of the bladder microbiome was associated with disease profile. For example, the genera Megamonas and Phocaeicola were negatively correlated with serum complement C3, and Streptococcus was positively correlated with IgG. Conclusions: Our present study reveals associations between the bladder microbiome and the urinary metabolome, cytokines, and disease phenotypes. Our results could help identify biomarkers for SLE.

Lupus ◽  
2018 ◽  
Vol 27 (13) ◽  
pp. 2057-2068 ◽  
Author(s):  
Z-J Yin ◽  
B-M Ju ◽  
L Zhu ◽  
N Hu ◽  
J Luo ◽  
...  

Objective The increment of CD4+CD25−Foxp3+T cells has been reported in systemic lupus erythematosus (SLE) patients. However, the exact identity of this T cell subset is still unclear. Thus, we analyzed CD4+CD25−Foxp3+T cells and Treg cells (CD4+CD25+Foxp3+ T cells) in a large sample of Chinese SLE patients in different disease states. Methods A total of 280 SLE patients and 38 healthy volunteers were enrolled, which included 21 patients with untreated new-onset lupus (UNOL), 13 patients with drug withdrawal more than 6 months and 246 patients with treatments. Phenotypic and functional analysis of peripheral blood CD4+CD25−Foxp3+ T cells and Treg cells were performed by flow cytometry. The correlation of CD4+CD25−Foxp3+T cells and Treg cells with disease activity, clinical indicators and organ involvement were analyzed. Results CD4+CD25−Foxp3+ T cells and Treg cells were significantly increased in SLE patients and showed significantly positive correlations with disease activity. CD4+CD25−Foxp3+ T cells were significantly increased in patients with skin and hematologic involvement as well as arthritis. Diverse changes between CD4+CD25−Foxp3+ T cells and Treg cells when faced with different medications, especially HCQ and MMF. CD4+CD25−Foxp3+ T cells expressed more IFN-γ and less CTLA-4 than CD4+CD25+Foxp3+ T cells, which were similar to CD4+CD25+Foxp3− T cells, and expressed similar IL-17, ICOS and Helios to CD4+CD25+Foxp3+ T cells. The synthesis capacity of IL-10 of CD4+CD25−Foxp3+ T cells and the expression of GITR on CD4+CD25−Foxp3+ T cells were between CD4+CD25+Foxp3+ and CD4+CD25+Foxp3− T cells. Conclusions Our results indicate that increased CD4+CD25−Foxp3+ T cells in lupus patients, which combined the features of suppression and pro-inflammatory, may serve as a biomarker for disease activity and organ involvement in SLE.


2016 ◽  
Vol 26 (6) ◽  
pp. 914-922 ◽  
Author(s):  
Bei Yan ◽  
Jia Huang ◽  
Chunmei Zhang ◽  
Xin Hu ◽  
Ming Gao ◽  
...  

2018 ◽  
Vol 45 (6) ◽  
pp. 827-834 ◽  
Author(s):  
Thomas C. Raissi ◽  
Carly Hewson ◽  
Janet E. Pope

Objective.Patients with systemic lupus erythematosus (SLE) frequently undergo repeat testing for antibodies against extractable nuclear antigens (anti-ENA), but it is not known whether this is necessary or cost-effective. This study characterized the frequencies of changes in anti-ENA, anti–dsDNA, and complement C3 and C4 upon repeat testing.Methods.Chart review was done at one site of 130 patients with SLE enrolled in the 1000 Canadian Faces of Lupus prospective registry with annual antibody and complement testing. We determined the frequency of seroconversion (changes) on the next test and over the entire followup given 1 or multiple consistent results, and the cost to detect these changes.Results.Overall, 89.4% of patients had no changes in anti-ENA screening results from the first available test, 3.3% changed from negative to positive, and 7.3% from positive to negative. Following a single anti-ENA test, 3.9% of negative tests changed to positive and 4.2% of positive changed to negative on the next test. After multiple consistent tests, the frequencies of changes progressively declined. No changes from the first test were observed in anti-dsDNA, C3, and C4 in 60.8%, 83.3%, and 75.4% of patients, respectively. After 2 consistent anti-ENA tests, the cost to detect 1 change was above US$2000.Conclusion.Anti-ENA results change infrequently, especially following 1 or more negative tests. The high cost and lack of evidence that changes affect management suggest that repeating anti-ENA tests routinely is unnecessary. Anti-dsDNA and complements change more frequently after an abnormal result, but less after a normal value.


2018 ◽  
Vol 10 (02) ◽  
pp. 232-236 ◽  
Author(s):  
Parisa Afzali ◽  
Anna Isaeian ◽  
Peyman Sadeghi ◽  
Bobak Moazzami ◽  
Nima Parvaneh ◽  
...  

Abstract BACKGROUND: Pediatric-onset systemic lupus erythematosus (pSLE) accounts for about 10%-20% of all patients with SLE. Deficiencies in early complement components of the classical pathway are the strong genetic risk factor for the development of SLE. In this study, clinical and laboratory manifestations of both complement-deficient and normal complement pSLE patients were compared. MATERIALS AND METHODS: To investigate clinical and immunological manifestations of pSLE in Iran, 36 consecutive pSLE patients (onset before 18 years) who were followed up over a period of 2 years, were studied. Complement C1q and C2 levels were measured using radial immunodifusion assay and complement C3 and C4 levels were measured using nephelometry. Medical records were retrospectively evaluated from patient database of Children Medical Center Hospital. Data were assessed through descriptive analysis (confidence interval = 95%), paired t-test, and Pearson correlation test. RESULTS: Twenty-one patients (58%) had at least one component of complement deficiency. Ten patients (27%) had low C1q level, 11 patients (30.5%) had low C2, nine patients (25%) had low C3, and four patients (11%) had low C4 level. Serum level of complement in pSLE was significantly lower than the control group, except C4 (P = 0.005). The low C1q patients had an earlier age of onset of disease (P < 0.0001). The cutaneous manifestations were more frequent and much more severe in pSLE with low complement (100% vs. 73%). The frequency of renal and musculoskeletal symptoms was equal, but renal morbidity was more common in pSLE with low complement. Positivity for anti-ds-DNA was less common in pSLE with low complement (71% vs. 86%). CONCLUSION: In pSLE patients with early disease onset and more aggressive SLE manifestations and negative anti-ds-DNA test, complement deficiency should be considered.


2020 ◽  
Vol 87 (3) ◽  
pp. 360-363
Author(s):  
Diego Araújo Frazilio ◽  
Otávio Guilherme Gonçalves de Almeida ◽  
Carlos Augusto Fernandes de Oliveira ◽  
Sarah Hwa In Lee ◽  
Carlos Humberto Corassin ◽  
...  

AbstractFor this research communication, 90 samples of a Brazilian dairy were combined into four groups (raw material, final product, food-contact and non-food contact surfaces) and analyzed by metataxonomics based on 16S rRNA gene sequencing. The results showed high alpha-diversity indexes for final product and non-food contact surfaces but, overall, beta-diversity indexes were low. The samples were separated in two main clusters, and the core microbiota was composed by Macrococcus, Alkaliphilus, Vagococcus, Lactobacillus, Marinilactibacillus, Streptococcus, Lysinibacillus, Staphylococcus, Clostridium, Halomonas, Lactococcus, Enterococcus, Bacillus and Psychrobacter. These results highlight that rare taxa occur in dairies, and this may aid the development of strategies for food protection.


2018 ◽  
Vol 77 (12) ◽  
pp. 1810-1814 ◽  
Author(s):  
Lucas L van den Hoogen ◽  
Joël A G van Roon ◽  
Jorre S Mertens ◽  
Judith Wienke ◽  
Ana Pinheiro Lopes ◽  
...  

ObjectiveThe interferon (IFN) signature is related to disease activity and vascular disease in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) and represents a promising therapeutic target. Quantification of the IFN signature is currently performed by gene expression analysis, limiting its current applicability in clinical practice. Therefore, the objective of this study was to establish an easy to measure biomarker for the IFN signature.MethodsSerum levels of galectin-9, CXCL-10 (IP-10) and tumour necrosis factor receptor type II (TNF-RII) were measured in patients with SLE, SLE+APS and primary APS (PAPS) and healthy controls (n=148) after an initial screening of serum analytes in a smaller cohort (n=43). Analytes were correlated to measures of disease activity and the IFN signature. The performance of galectin-9, CXCL-10 and TNF-RII as biomarkers to detect the IFN signature was assessed by receiver operating characteristic curves.ResultsGalectin-9, CXCL-10 and TNF-RII were elevated in patients with SLE, SLE+APS and PAPS (p<0.05) and correlated with disease activity and tissue factor expression. Galectin-9 correlated stronger than CXCL-10 or TNF-RII with the IFN score (r=0.70, p<0.001) and was superior to CXCL-10 or TNF-RII in detecting the IFN signature (area under the curve (AUC) 0.86). Importantly, in patients with SLE(±APS), galectin-9 was also superior to anti-dsDNA antibody (AUC 0.70), or complement C3 (AUC 0.70) and C4 (AUC 0.78) levels in detecting the IFN signature.ConclusionGalectin-9 is a novel, easy to measure hence clinically applicable biomarker to detect the IFN signature in patients with systemic autoimmune diseases such as SLE and APS.


2020 ◽  
Vol 88 (12) ◽  
Author(s):  
Eric L. Brown ◽  
Heather T. Essigmann ◽  
Kristi L. Hoffman ◽  
Noah W. Palm ◽  
Sarah M. Gunter ◽  
...  

ABSTRACT Mucosal surfaces like those present in the lung, gut, and mouth interface with distinct external environments. These mucosal gateways are not only portals of entry for potential pathogens but also homes to microbial communities that impact host health. Secretory immunoglobulin A (SIgA) is the single most abundant acquired immune component secreted onto mucosal surfaces and, via the process of immune exclusion, shapes the architecture of these microbiomes. Not all microorganisms at mucosal surfaces are targeted by SIgA; therefore, a better understanding of the SIgA-coated fraction may identify the microbial constituents that stimulate host immune responses in the context of health and disease. Chronic diseases like type 2 diabetes are associated with altered microbial communities (dysbiosis) that in turn affect immune-mediated homeostasis. 16S rRNA gene sequencing of SIgA-coated/uncoated bacteria (IgA-Biome) was conducted on stool and saliva samples of normoglycemic participants and individuals with prediabetes or diabetes (n = 8/group). These analyses demonstrated shifts in relative abundance in the IgA-Biome profiles between normoglycemic, prediabetic, or diabetic samples distinct from that of the overall microbiome. Differences in IgA-Biome alpha diversity were apparent for both stool and saliva, while overarching bacterial community differences (beta diversity) were also observed in saliva. These data suggest that IgA-Biome analyses can be used to identify novel microbial signatures associated with diabetes and support the need for further studies exploring these communities. Ultimately, an understanding of the IgA-Biome may promote the development of novel strategies to restructure the microbiome as a means of preventing or treating diseases associated with dysbiosis at mucosal surfaces.


Animals ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 2125
Author(s):  
Limin Wei ◽  
Bo Zeng ◽  
Siyuan Zhang ◽  
Feng Li ◽  
Fanli Kong ◽  
...  

The gut microbiota coevolve with the host and can be stably transmitted to the offspring. Host genetics plays a crucial role in the composition and abundance of gut microbiota. Inbreeding can cause a decrease of the host’s genetic diversity and the heterozygosity. In this study, we used 16S rRNA gene sequencing to compare the differences of gut microbiota between the Diannan small-ear pig and Banna minipig inbred, aiming to understand the impact of inbreeding on the gut microbiota. Three dominant bacteria (Stenotrophlomonas, Streptococcus, and Lactobacillus) were steadily enriched in both the Diannan small-ear pig and Banna minipig inbred. After inbreeding, the gut microbiota alpha diversity and some potential probiotics (Bifidobacterium, Tricibacter, Ruminocaccae, Christensenellaceae, etc.) were significantly decreased, while the pathogenic Klebsiella bacteria was significantly increased. In addition, the predicted metagenomic analysis (PICRUSt2) indicated that several amino acid metabolisms (‘‘Valine, leucine, and isoleucine metabolism’’, ‘‘Phenylalanine, tyrosine, and tryptophan biosynthesis’’, ‘‘Histidine metabolism’’) were also markedly decreased after the inbreeding. Altogether our data reveal that host inbreeding altered the composition and the predicted function of the gut microbiome, which provides some data for the gut microbiota during inbreeding.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sebastian von Huth ◽  
Louise Bruun Thingholm ◽  
Corinna Bang ◽  
Malte C. Rühlemann ◽  
Andre Franke ◽  
...  

AbstractThe gut microbiota is recognized as having major impact in health and disease. Sample storage is an important aspect to obtain reliable results. Mostly recommended is immediate freezing, however, this is not always feasible. Faecal occult blood test (FOBT) papers are an appealing solution in such situations, and most studies find these to be applicable, showing no major changes within 7 days storage at room temperature (RT). As fieldwork often requires RT storage for longer periods, evaluation of this is warranted. We performed 16S rRNA gene sequencing of 19 paired faecal samples immediately frozen or kept five weeks and five months at RT on FOBT papers. Alpha-diversity evaluation revealed no effect of FOBT storage, and evaluation of beta-diversity showed that host explained 65% of community variation, while storage method explained 5%. Evaluation of community dispersion and the Firmicutes/Bacteroidetes ratio revealed a larger effect of storage time for fresh-frozen samples. Single taxa evaluation (order-to-genus level) showed significant alterations of four (of 37) genera after five weeks and five genera after five months. When comparing the two timepoints, alterations were only detectable for fresh-frozen samples. Our findings reveal that long term storage on FOBT papers is an applicable approach for microbiota research.


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