scholarly journals Colon epithelial barrier state in children with varios types of ulcerative colitis clinical forms

Author(s):  
M.F. Denisova ◽  
◽  
T.D. Zadorojna ◽  
N.Y. Bukulova ◽  
T.M. Archakova ◽  
...  

Purpose — analyse the state of the epithelial barrier of the colon in children with different clinical forms. Materials and methods. 42 children with acute chronic colitis were examined, including 28 with ulcerative colitis (14 with active total form, 14 with moderately active segmental); and 14 with chronic non-specific opaque colitis formed a comparison group. Laboratory methods were performed on all patients — hemogram, protein-gram, blood biochemistry, fecal calprotectin concentration; endoscopic examination with biopsy of all colon regions and histological examination of biopts. Results. The clinical manifestations of ulcerative colitis (UC) during the acute period were assessed by the Paediatric Activity Index (PUCAI) and depended on the localization and activity of the inflammatory process. The average for active colitis was found to be 50.2±1.8, moderate to 35.3±1.7, minimum to 24.1±1.2, but for children with total active inflammation 19 per cent of patients had the highest rates: 65, which corresponded to clinical signs of ulcerative colitis, accompanied by unidirectional changes of surface (dystrophic changes of epithelium, crypt deformation, reduced number of flax cells) and deep (diffuse inflammatory infiltration of its own plate, presence of crypt abscesses, cryptites, vascular dilation) structures of the mucous membrane of the large intestine, which are more pronounced in the active total forms of ulcerative colitis. The period of UC exacerbation is characterized by the violation of the epithelial barrier mucous membrane colon due to reduced mucus synthesis and changes in its biochemical properties, low secretory (MUC2) and membrane-associated (MUC4) expression Mucins, mainly in the active total forms of UC, loss of the regulatory effect of the club peptide on regeneration and protection of the mucous membrane of the intestine. Conclusions. Studies based on a pathogenetic approach to determining the cause of the exacerbation of the disease have shown evidence of a significant role in the epithelial barrier of the colon membrane, This is a significant addition to the known knowledge of ulcerative colitis pathogenesis in childhood. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of these Institutes. The informed consent of the patient was obtained for conducting the studies. The authors declare no conflicts of interests. Key words: ulcerative colitis, children, epithelial barrier, mucins, clubs.

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S38-S38
Author(s):  
Chen Sarbagili-Shabat ◽  
Lindsey Albenberg ◽  
Johan Van Limbergen ◽  
Dror Weiner ◽  
Michal Yaakov ◽  
...  

Abstract Background Newer strategies that target the microbiome may offer an alternative therapeutic approach for Ulcerative Colitis (UC). We developed a novel diet that targets changes in the microbiome and barrier function that have been reported in UC. The goal of the current study was to evaluate the efficacy of two sequential induction of remission strategies that target the microbiota: the novel diet termed the ulcerative colitis diet (UCD) and an antibiotics cocktail combination in dietary non responders. Methods This was a prospective, single arm, open label, pilot study in patients aged 8–19, with a pediatric UC activity index (PUCAI) scores >10 and ≤45 on stable maintenance therapy (5ASA or thiopurines). PUCAI score was assessed at week 3 and 6. Patients failing to enter remission or intolerant to dietary therapy could receive an open label 14-day course of Amoxycillin, Metronidazole and Doxycycline (AMD), and had PUCAI scored at day 21. Response was defined a decline in PUCAI ≥ 10 points, remission as PUCAI< 10. The primary endpoint was intention to treat (ITT) remission at week 6 with diet as the sole intervention. Results Twenty-three children mean age of 15.1±2.9 years were enrolled. Two patients (1 responder, 1 remission) withdrew by 3 weeks, four required additional therapy by week 3, all were considered failures by ITT. Mean PUCAI decreased at week 3 and 6 from 34.5±9.8 to 21.7±14.9 and 17.6±17.2 respectively (P=0.005, P=0.001) at ITT analysis including all patients. Sixteen out of twenty-three patients (69.6%) responded by week 6. Ten of twenty-three (43.5%) achieved remission by week 6, and nine (39.1%) had clinical remission at week 6. The median fecal calprotectin (FC) level decreased in patients (n=5) who achieved remission from 630 (IQR, 332–1586) μg/g at week 0 to 230 (75–1298) μg/g at week 6. Eight patients received treatment with antibiotics after failing diet, 4/8 (50.0%) subsequently entered remission. Conclusion A dietary intervention called the UC Diet appears to be effective for induction of remission in children with mild to moderate UC. Sequential use of diet, followed by antibiotic therapy in dietary non responders, needs further evaluation as a microbiome directed steroid sparing therapy in patient’s refractory to 5ASA and thiopurines.


Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3598
Author(s):  
Bridgette Wilson ◽  
Özge Eyice ◽  
Ioannis Koumoutsos ◽  
Miranda C. Lomer ◽  
Peter M. Irving ◽  
...  

Prebiotics may promote immune homeostasis and reduce sub-clinical inflammation in humans. This study investigated the effect of prebiotic galactooligosaccharide (GOS) supplementation in colonic inflammation. Seventeen patients with active ulcerative colitis (UC) consumed 2.8 g/d GOS for 6 weeks. At baseline and 6 weeks, gene expression (microarray), fecal calprotectin (ELISA), microbiota (16S rRNA), short-chain fatty acids (SCFAs; gas-liquid chromatography), and clinical outcomes (simple clinical colitis activity index (SCCAI), gastrointestinal symptom rating scale (GSRS), and Bristol stool form scale (BSFS)) were measured. Following prebiotics, clinical scores (SCCAI), fecal calprotectin, SCFAs, and pH were unchanged. Five genes were upregulated and two downregulated. Normal stool proportion (BSFS) increased (49% vs. 70%, p = 0.024), and the incidence (46% vs. 23%, p = 0.016) and severity (0.7 vs. 0.5, p = 0.048) of loose stool (GSRS), along with urgency (SCCAI) scores (1.0 vs. 0.5, p = 0.011), were reduced. In patients with a baseline SCCAI ≤2, prebiotics increased the relative abundance of Bifidobacterium from 1.65% (1.97) to 3.99% (5.37) (p = 0.046) and Christensenellaceae from 0.13% (0.33) to 0.31% (0.76) (p = 0.043). Prebiotics did not lower clinical scores or inflammation but normalized stools. Bifidobacterium and Christensenellaceae proportions only increased in patients with less active diseases, indicating that the prebiotic effect may depend on disease activity. A controlled study is required to validate these observations.


Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 523 ◽  
Author(s):  
Gionata Fiorino ◽  
Giacomo Carlo Sturniolo ◽  
Fabrizio Bossa ◽  
Andrea Cassinotti ◽  
Antonio Di Sabatino ◽  
...  

IBD98-M is a delayed-release formulation of mesalamine (mesalazine) and SH with a potential therapeutic role in ulcerative colitis (UC). A total of 51 patients with a modified Ulcerative Colitis Disease Activity Index (UCDAI) score of ≥4 and ≤10, and a modified UCDAI endoscopy subscore ≥1 were randomized for 6 weeks of double-blind treatment with IBD98 0.8 g/day or IBD 1.2 g/day or placebo. The efficacy and safety of IBD98-M in mild to moderate active UC were primarily evaluated. At week 6, 1 (5.9%), 2 (12.5%), and 2 (11.1%) patients receiving IBD98-M 0.8 g, IBD98-M 1.2 g, and placebo, respectively, (p > 0.999) achieved clinical remission. Higher clinical response was seen in IBD98-M 1.2 g (31.3%) versus placebo (16.7%) and endoscopic improvement in IBD98-M 0.8 g (29.4%) versus placebo (22.2%) was seen. Fecal calprotectin levels were reduced in IBD98-M groups versus placebo (p > 0.05). IBD98-M patients achieved significant improvement in physical health summary score component of the SF-36 (p = 0.01 and p = 0.03 respectively) compared to placebo. IBD98-M did not meet the primary end point but had higher clinical response (1.2 g/day) and endoscopic improvement (0.8 g/day) compared to placebo. The safety result shown that IBD98-M treatment was safe and well tolerated in this patient population. No new safety signals or unexpected safety findings were observed during the study. Further trials with different stratification and longer follow-up may be needed to evaluate the efficacy.


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 15 (Supplement_1) ◽  
pp. S381-S382
Author(s):  
P Golovics ◽  
L Gonczi ◽  
J Reinglass ◽  
C Verdon ◽  
S Pundir ◽  
...  

Abstract Background Optimal management of patients with ulcerative colitis (UC) requires the accurate assessment of disease activity. Endoscopic evaluation is considered the gold standard approach, but it is invasive. We aimed to determine how strong patient reported outcomes, clinical scores and symptoms correlate with endoscopy for assessment of disease activity in UC patients. Methods 171 patients were included prospectively and consecutively (age: 49 (IQR: 38-61) years, duration 12 (4-19)years, 79 females (46.2%), 57.3% extensive disease, 42.7% on biologicals) at the time of the colonoscopy. The 2 item patient reported outcome (PRO), partial MAYO, Simple Clinical Colitis Activity Index (SCCAI), Mayo endoscopic subscore (MES), Baron and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) scores were calculated. C reactive Protein (CRP) and fecal calprotectin (FCAL) was available in 83 and 45.6% of patients. 17.0% had clinical flare, treatment was escalated in 14.6% of patients. Sensitivity, specificity, PPV and NPV values were calculated, ROC analysis and K-statistics were performed. Results Rectal bleeding (RBS), stool frequency (SF) subscore of 0, or total PRO2 remission (RBS 0 and SF ≤1), partial MAYO (≤2) and SCCAI (≤2.5) remission were similarly associated to mucosal healing defined by MES (0 or ≤1) or Baron (0 or ≤1) scores (Table 1). PRO2 (AUCMES0/Baron0: 0.770/0.740, AUCMES0-1/Baron0-1: 0.868/0.858), SF (AUCMES0/Baron0:0.751/0.724, AUCMES0-1/Baron0-1:0842/0.820), RBS (AUCMES0/Baron0: 0.718/0.698, AUCMES0-1/Baron0-1: 0.814/0.845) partial Mayo (AUCMES0/Baron0: 0.823/0.788, AUCMES0-1/Baron0-1: 0.927/0.902) and SCCAI (AUCMES0/Baron0: 0.767/0.752, AUCMES0-1/Baron0-1:0.888/0.867) were similarly associated with mucosal healing in a ROC analysis. There was a strict association between MES 0 and Baron 0 (k=0.917) and UCEIS &lt;4 and MES 0-1 (k=0.813), while moderate to fair agreement between UCEIS &lt;4 and MES 0 (K=0.471) or Baron 0 (K=0.414)/Baron 0-1 (K=0.353), and between MES 0-1 and Baron 0-1 (K= 0.350) scores. Agreement between CRP and clinical remission or endoscopic healing (MES/Baron) was poor (K~0.2), while agreement between FCAL (&gt;100 or &gt;250) and RBS-PRO2 remission (K&gt;100 or &gt;250: 0.44-0.60) or pMAYO (K&gt;100 or &gt;250: 0.41-0.59) or MES/Baron 0 was moderate to good (K&gt;100:0.53-0.52 and K&gt;250:0.57-0.53). Conclusion We found no difference across accuracy of RBS, SF, PRO2, partial Mayo and SCCAI in predicting endoscopic healing. A strong association was found with high PPV for MES/Baron ≤1 and high NPV for MES/Baron 0. FCAL, but not CRP was associated to clinical and endoscopic remission.


2014 ◽  
Vol 10 (3) ◽  
pp. 321-328 ◽  
Author(s):  
Tarang Taghvaei ◽  
Iradj Maleki ◽  
Farshad Nagshvar ◽  
Hafez Fakheri ◽  
Vahid Hosseini ◽  
...  

Author(s):  
Денисова М. Ф. ◽  
Букулова Н. Ю.

This article presents frequency of occurrence of clinical forms of the disease depending on the localization and activity of the inflammatory process, their age and gender differences, risk factors and disease triggers, based on a retrospective analysis of 116 cases of children with ulcerative colitis at the age of 4-18 years. Comparative clinical, laboratory and endoscopic characteristics of total, segmental and distal colitis have been also analyzed. It was found that clinical activity of total colitis is characterized by more severe course of the disease, accompanied with systemic and local extraintestinal manifestations (OR = 4,504±0,506, p<0.05), more pronounced changes in hemo- and proteinogram parameters (p<0.05). Endoscopic criteria for differences in the clinical forms of ulcerative colitis are the presence of ulcers (OR = 9,667±0,645, p <0,05), erosions (OR = 3,569±0,429, p<0,05), contact bleeding (OR = 4,364± ,444, p< 0.05), changes in the vascular pattern (OR = 3,748±0,477, p<0.05). Correlation analysis of the relationship between clinical (PUCAI), endoscopic (Rachmilewitz index) and laboratory markers of the inflammatory process (leukocytes, platelets, erythrocyte sedimentation rate, γ-globulins, fecal calprotectin, hemoglobin) has been also performed, the criteria of which might be used to monitor the course of the disease and the effectiveness of therapy.


2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S418-S419
Author(s):  
F de Voogd ◽  
M Duijvestein ◽  
C Ponsioen ◽  
M Löwenberg ◽  
G D’Haens ◽  
...  

Abstract Background Submucosal fibrosis in ulcerative colitis (UC) has been associated with disease severity in colectomy specimens. As intestinal ultrasound (IUS) visualizes all individual wall layers, we aimed to evaluate baseline IUS features to determine endoscopic response and investigate changes in wall layers during anti-inflammatory treatment in patients with UC Methods Moderate-severe UC patients (endoscopic Mayo score (EMS)≥2) extending beyond the rectum starting treatment were included. Simple Clinical Colitis Activity Index (SCCAI), fecal calprotectin (FCP), IUS and endoscopy were performed at baseline and at follow-up between week 8 and 26. BWT, individual wall layer thickness (WT) (mucosa (MC), submucosa (SM) and muscularis propria (MP)) and ratios among layers, Colour Doppler Signal, loss of haustrations, loss of stratification and hyperechogenicity of the submucosa (HoS) (Figure 1) were scored for the sigmoid colon (SC). EMS was assessed for the SC: endoscopic remission (ER) was defined as EMS=0 and endoscopic improvement (EI) as EMS≤1. For statistical analysis a paired t-test and X2-test were used. Results 49 patients were included of whom 61% failed ≥1 biological. 59% started tofacitinib and 41% started a biological. At follow-up, 30% and 49% reached ER and EI, respectively. BWT decreased significantly when ER (2.32 ± 1.63 mm vs 1.00 ± 1.98 mm, p=0.034) or EI (2.53 ± 1.66 mm vs 0.30 ± 1.58 mm, p&lt;0.0001) was reached. In patients with ER and EI, the SM thickness showed significantly more pronounced decrease compared to the other wall layers (Table 1 and Figure 2). Baseline presence of HoS (29% of patients) predicted failure of treatment (ER: OR: 0.10, 95% CI: 0.01-0.87, p=0.014, EI: OR: 0.16, 95% CI: 0.04-0.65, p=0.008,). Furthermore, when HoS was present, SCCAI (7.33 ± 3.62 vs 9.75 ± 3.23, p=0.023) and FCP (1249 ± 903 µg/g vs 2494 ± 2277 µg/g, p=0.008) were significantly lower at baseline. Also, patients with HoS more frequently failed one (OR: 4.44, 95% CI: 1.08-18.32, p=0.03) or multiple biologicals (OR: 5.63, 95% CI: 1.54-20.52, p=0.009). However, disease duration (p=0.950) or age at onset (p=0.853) did not differ between groups. Conclusion This is the first study showing that HoS on IUS is a predictor of endoscopic non-response to biologicals and tofacitinib in patients with UC. Additionally, changes in SM layer thickness is the most important component of the total bowel wall when evaluating mucosal healing on IUS.


2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Kaija-Leena Kolho ◽  
Dan Turner

Objective. To explore fecal calprotectin levels in pediatric ulcerative colitis (UC) in relation with the validated clinical activity index PUCAI. Methods. This study included all 37 children (median age 14 years) with UC who had calprotectin measured (PhiCal ELISA Test) by the time of PUCAI assessment at the Children's Hospital of Helsinki in a total of 62 visits. Calprotectin values <100 μg/g of stool were considered as normal. The best cut-off value of each measure to predict 3-month clinical outcome was derived by maximizing sensitivity and specificity. Results. In clinically active disease (PUCAI ≥ 10), calprotectin was elevated in 29/32 patients (91% sensitivity). When in clinical remission, 26% (8/30) of the children had normal calprotectin but 7 (23%) had an exceedingly high level (>1000 μg/g). The best cut-off value for calprotectin for predicting poor outcome was 800 μg/g (sensitivity 73%, specificity 72%; area under the ROC curve being 0.71 (95%CI 0.57–0.85)) and for the PUCAI best cut-off values >10 (sensitivity 62%, specificity 64%; area under the ROC curve 0.714 (95%CI 0.58–0.85)). Conclusion. The clinical relevance of somewhat elevated calprotectin during clinical remission in pediatric UC is not known and, until further evidence accumulates, does not indicate therapy escalation.


2021 ◽  
Vol 11 ◽  
Author(s):  
Zhiwei Miao ◽  
Liping Chen ◽  
Hui Feng ◽  
Mingjia Gu ◽  
Jing Yan ◽  
...  

Ulcerative colitis (UC) is a chronic intestinal disease with unclear pathogenesis. With an increasing global prevalence over the past two decades, UC poses a serious threat to public health. Baitouweng decoction (BTW), a traditional Chinese medicine, has been shown to have good clinical efficacy for treating intestinal inflammation. Yet, the efficacy of BTW in UC and the underlying mechanism remain unclear. The current study aimed to determine whether BTW suppressed intestinal inflammation in mice and the potential mechanism. We used a dextran sulfate sodium (DSS)-induced murine colitis model to test the anti-inflammatory efficacy of BTW. Clinical symptoms were scored by the disease activity index (DAI), and the colon length and pathological changes in colon tissue were also used to further evaluate the efficacy of BTW. Precisely how BTW affected immune function and the intestinal barrier of UC mice was also examined. BTW significantly reduced DAI score and colonic pathological damage. BTW regulated the balance between T helper (Th)17 and regulatory T (Treg) cells, decreased interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, and increased IL-10 levels. BTW reduced intestinal permeability of UC mice, increased expression of tight junction proteins (occludin and zonula occludens-1), and decreased expression of phospho-nuclear factor (p-NF)-κB and phospho-extracellular signal-regulated kinase (p-ERK) in the colon. BTW inhibited the ERK/p-NF-κB signaling pathway and suppressed expression of cyclo-oxygenase-2 and inducible NO synthase in lipopolysaccharide-activated RAW 264.7 cells. BTW significantly promoted the synthesis of short-chain fatty acids in the gut, particularly acetate, propionate, isobutyric acid, and isovalerate. The results suggest that BTW can protect against DSS-induced UC. The mechanism may be partially attributed to regulating the balance of Th17/Treg cells and restoring the intestinal epithelial barrier.


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