scholarly journals VSL#3 Probiotic Upregulates Intestinal Mucosal Alkaline Sphingomyelinase and Reduces Inflammation

2008 ◽  
Vol 22 (3) ◽  
pp. 237-242 ◽  
Author(s):  
Isaac Soo ◽  
Karen L Madsen ◽  
Qassim Tejpar ◽  
Beate C Sydora ◽  
Richard Sherbaniuk ◽  
...  

BACKGROUND: Alkaline sphingomyelinase, an enzyme found exclusively in bile and the intestinal brush border, hydrolyzes sphingomyelin into ceramide, sphingosine and sphingosine-1-phosphate, thereby inducing epithelial apoptosis. Reduced levels of alkaline sphingomyelinase have been found in premalignant and malignant intestinal epithelia and in ulcerative colitis tissue. Probiotic bacteria can be a source of sphingomyelinase.OBJECTIVE: To determine the effect of VSL#3 probiotic therapy on mucosal levels of alkaline sphingomyelinase, both in a mouse model of colitis and in patients with ulcerative colitis.METHODS: Interleukin-10 gene-deficient (IL10KO) and wild type control mice were treated with VSL#3 (109colony-forming units per day) for three weeks, after which alkaline sphingomyelinase activity was measured in ileal and colonic tissue. As well, 15 patients with ulcerative colitis were treated with VSL#3 (900 billion bacteria two times per day for five weeks). Alkaline sphingomyelinase activity was measured through biopsies and comparison of ulcerative colitis disease activity index scores obtained before and after treatment.RESULTS: Lowered alkaline sphingomyelinase levels were seen in the colon (P=0.02) and ileum (P=0.04) of IL10KO mice, as compared with controls. Treatment of these mice with VSL#3 resulted in upregulation of mucosal alkaline sphingomyelinase activity in both the colon (P=0.04) and the ileum (P=0.01). VSL#3 treatment of human patients who had ulcerative colitis decreased mean (± SEM) ulcerative colitis disease activity index scores from 5.3±1.8946 to 0.70±0.34 (P=0.02) and increased mucosal alkaline sphingomyelinase activity.CONCLUSION: Mucosal alkaline sphingomyelinase activity is reduced in the intestine of IL10KO mice with colitis and in humans with ulcerative colitis. VSL#3 probiotic therapy upregulates mucosal alkaline sphingomyelinase activity.

1990 ◽  
Vol 4 (7) ◽  
pp. 468-471 ◽  
Author(s):  
MG Robinson ◽  
DL Decktor

The efficacy of 4 g 5-aminosalicylic acid (5-ASA, mesalamine) enemas was assessed in 666 patients with distal ulcerative colitis. Patients were enrolled in an open-label compassionate use program. One 4 g 5-ASA enema was administered each night for a period of four weeks and the disease activity index was assessed at baseline and on days 14 and 28. On days 14 and 28, 78.0% and 88.1% of patients, respectively, demonstrated an improvement in disease activity index. The mean decline in disease activity index on day 14 was 40.7% (P=0.0001) and on day 28 it was 55.4% (P=0.0001). Efficacy was similar whether the disease was confined to or extended beyond 30 cm from the anus. There was no difference in efficacy in patients suffering their first episode of disease compared to patients suffering subsequent attacks. In conclusion, high dose 5-ASA enemas are a highly effective treatment for distal ulcerative colitis.


2018 ◽  
Vol 154 (6) ◽  
pp. S-587-S-588
Author(s):  
Steven Bots ◽  
Kim Nylund ◽  
Mark Löwenberg ◽  
Krisztina Gecse ◽  
Odd Helge Gilja ◽  
...  

2018 ◽  
Vol 56 (10) ◽  
pp. 1267-1275 ◽  
Author(s):  
Angelika Hüppe ◽  
Jana Langbrandtner ◽  
Winfried Häuser ◽  
Heiner Raspe ◽  
Bernd Bokemeyer

Abstract Introduction Assessment of disease activity in Crohn’s disease (CD) and ulcerative colitis (UC) is usually based on the physician’s evaluation of clinical symptoms, endoscopic findings, and biomarker analysis. The German Inflammatory Bowel Disease Activity Index for CD (GIBDICD) and UC (GIBDIUC) uses data from patient-reported questionnaires. It is unclear to what extent the GIBDI agrees with the physicians’ documented activity indices. Methods Data from 2 studies were reanalyzed. In both, gastroenterologists had documented disease activity in UC with the partial Mayo Score (pMS) and in CD with the Harvey Bradshaw Index (HBI). Patient-completed GIBDI questionnaires had also been assessed. The analysis sample consisted of 151 UC and 150 CD patients. Kappa coefficients were determined as agreement measurements. Results Rank correlations were 0.56 (pMS, GIBDIUC) and 0.57 (HBI, GIBDICD), with p < 0.001. The absolute agreement for 2 categories of disease activity (remission yes/no) was 74.2 % (UC) and 76.6 % (CD), and for 4 categories (none/mild/moderate/severe) 60.3 % (UC) and 61.9 % (CD). The kappa values ranged between 0.47 for UC (2 categories) and 0.58 for CD (4 categories). Discussion There is satisfactory agreement of GIBDI with the physician-documented disease activity indices. GIBDI can be used in health care research without access to assessments of medical practitioners. In clinical practice, the index offers a supplementary source of information.


2014 ◽  
Vol 51 (2) ◽  
pp. 107-112 ◽  
Author(s):  
Luiz Gustavo de OLIVEIRA ◽  
André Luiz da CUNHA ◽  
Amaury Caiafa DUARTE ◽  
Maria Christina Marques Nogueira CASTAÑON ◽  
Júlio Maria Fonseca CHEBLI ◽  
...  

ContextInflammatory bowel disease, including ulcerative colitis and Crohn’s disease, comprising a broad spectrum of diseases those have in common chronic inflammation of the gastrointestinal tract, histological alterations and an increased activity levels of certain enzymes, such as, metalloproteinases.ObjectivesEvaluate a possible correlation of disease activity index with the severity of colonic mucosal damage and increased activity of metalloproteinases in a model of ulcerative colitis induced by dextran sulfate sodium.MethodsColitis was induced by oral administration of 5% dextran sulfate sodium for seven days in this group (n=10), whereas control group (n=16) received water. Effects were analyzed daily by disease activity index. In the seventh day, animals were euthanized and hematological measurements, histological changes (hematoxylin and eosin and Alcian Blue staining), myeloperoxidase and metalloproteinase activities (MMP-2 and MMP-9) were determined.ResultsDextran sulfate sodium group showed elevated disease activity index and reduced hematological parameters. Induction of colitis caused tissue injury with loss of mucin and increased myeloperoxidase (P<0.001) and MMP-9 activities (45 fold) compared to the control group.ConclusionsIn this study, we observed a disease activity index correlation with the degree of histopathological changes after induction of colitis, and this result may be related mainly to the increased activity of MMP-9 and mieloperoxidase.


2009 ◽  
Vol 136 (5) ◽  
pp. A-161
Author(s):  
Dan Turner ◽  
Cynthia H. Seow ◽  
Mark S. Silverberg ◽  
Gordon R. Greenberg ◽  
Anne M. Griffiths ◽  
...  

2013 ◽  
Vol 40 (12) ◽  
pp. 2029-2037 ◽  
Author(s):  
Fei Xiao ◽  
Hai-Yu Zhang ◽  
Yi-Jun Liu ◽  
Ding Zhao ◽  
Yu-Xing Shan ◽  
...  

Objective.The role of follicular Th (TFH) cells remains unclear in the pathogenesis of ankylosing spondylitis (AS). Our study examined the frequency of different subsets of circulating CXCR5+CD4+ T cells in patients with AS before and after receiving therapy.Methods.Percentages of peripheral blood inducible costimulator (ICOS)+, programmed death 1 (PD-1)+, and interleukin 21 (IL-21)+ CXCR5+CD4+ T cells in 26 patients with AS and 12 healthy controls (HC) were examined by flow cytometry, and the disease activity of individual patients was measured by Bath AS Disease Activity Index (BASDAI). The concentrations of serum IL-21, IgG, IgA, IgM, and C-reactive protein (CRP) were examined and the values of erythrocyte sedimentation rate (ESR) were measured. The potential association among these measures was analyzed.Results.In comparison with that in HC, significantly increased percentages of CXCR5+CD4+, CXCR5+CD4+PD-1+, and CXCR5+CD4+IL-21+, but not CXCR5+CD4+ICOS+ and PD-1+ICOS+CXCR5+CD4+ T cells, and elevated concentrations of serum IL-21 were detected in patients with AS (p = 0.001, p = 0.012, p < 0.001, p = 0.233, p = 0.216, p < 0.001, respectively). Treatment with meloxicam, thalidomide, and etanercept for 1 month significantly reduced percentages of IL-21+CXCR5+CD4+ T cells and concentrations of serum IL-21 (p < 0.001, p < 0.001, respectively), accompanied by significantly minimized disease activity in drug responders, but not in the drug nonresponders. Further, percentages of IL-21+CXCR5+CD4+ T cells were positively correlated with BASDAI in patients (r = 0.6, p = 0.0012) and in the drug-responders 1 month after treatment (r = 0.68, p = 0.005), while the percentages of PD-1+CXCR5+CD4+ T cells were negatively correlated with BASDAI (r = −0.58, p = 0.0018).Conclusion.These data suggest that IL-21+CXCR5+CD4+ T cells may be associated with development of AS and that the frequency of IL-21+CXCR5+CD4+ T cells may be a biomarker for evaluation of disease activity and drug responses in patients with AS, particularly in drug-responding patients.


2019 ◽  
Vol 12 (1) ◽  
pp. 34-38
Author(s):  
Kourosh Masnadi Shirazi ◽  
Sima Khayati ◽  
Maryam Baradaran Binazir ◽  
Zeinab Nikniaz

BACKGROUND Introducing a non-invasive method for determining disease activity is important in patients with ulcerative colitis (UC). So in this study, we aimed to assess the association between disease activity index and microalbuminuria in patients with UC. METHODS In the present cross-sectional study, 84 patients with UC were selected. The disease activity was calculated by the partial Mayo clinic score. Microalbuminuria was assessed using the immunoturbidimetric method in a first-voided sample in the morning in two consecutive days and the mean of these two measurements was reported as urinary microalbumin level. Serum C reactive protein (CRP), erythrocyte sedimentation rate (ESR), and fecal calprotectin were measured respectively using conventional turbidimetric immunoassay, Westergren method, and ELISA methods. RESULTS The mean age of the participants was 40.01 ± 12.85 years, 60.8% of them were female and 53.5% had microalbuminuria. The frequency of microalbuminuria was significantly higher in patients with active compared with inactive inflammatory bowel disease (IBD). There were significant differences between the patients with active and inactive disease regarding CRP, ESR, and calprotectin (p < 0.001). Moreover, there was a strong correlation between microalbuminuria and CRP (r = 0.89, p < 0.001), ESR (r = 0.92, p < 0.001), and calprotectin (r = 0.91, p < 0.001). CONCLUSION Microalbuminuria could be used as a non-invasive marker of disease activity in patients with UC.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Xi-Ying Li ◽  
Yan-Ting Yang ◽  
Yue Zhao ◽  
Xie-He Kong ◽  
Guang Yang ◽  
...  

Background. Moxibustion has been recognized as an effective approach for ulcerative colitis, yet its mechanism is not clear. The research aimed to investigate the influence of moxibustion on the activation of NLRP3 inflammasome and its mechanism in treating ulcerative colitis by observing miR7/RNF183 inducing IκB α ubiquitination to regulate NF-κB signaling pathway in an ulcerative colitis rat model. Methods. An ulcerative colitis rat model was established by unlimited access to self-administration of 3.5% (w/v) dextran sulfate sodium solution. Mild moxibustion was applied to bilateral Tianshu points (ST25) in the moxa-stick moxibustion group; rats in the control group were intervened by intraperitoneal injection of ubiquitination inhibitor, MG132. The disease activity index was determined at the end of the intervention; colon injury was observed and scored after hematoxylin-eosin staining; the immunohistochemical method was adopted to detect the expressions of colonic IL-1β and NLRP3 proteins; Western blot determined the expressions of RNF183, IκB α, and NF-κB p65 proteins in the colon; the immunofluorescence test was used to observe the coexpression of IκB α/ubiquitin and IκB α/RNF183 proteins in the colon; immunoprecipitation assay was adopted to observe the interaction between IκB α and RNF183 proteins; and quantitative real-time polymerase chain reaction determined the expression of colonic miR7. Results. Moxibustion lowered the disease activity index, manifesting as restored colonic tissue and reduced inflammatory reaction, and decreased expression levels of NLRP3 and IL-1β proteins, compared with the model group. It also reduced colonic expression of NF-κB p65 protein, together with the increased level of IκB α protein and weaker expression levels of ubiquitin and RNF183 proteins and mRNAs and stronger expression of miR7. There were no significant differences between the moxa-stick moxibustion group and the control group except the expressions of RNF183 protein and mRNA and miR7. Conclusion. Moxibustion encourages the recovery of colon injury probably by regulating the expression of NLRP3 protein in ulcerative colitis rats through miR7/RNF183/NF-κB signaling pathway.


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