scholarly journals Prebiotic Galactooligosaccharide Supplementation in Adults with Ulcerative Colitis: Exploring the Impact on Peripheral Blood Gene Expression, Gut Microbiota, and Clinical Symptoms

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.

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.


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 ◽  
...  

2016 ◽  
Vol 12 (1) ◽  
pp. 126
Author(s):  
D. Jørgensen ◽  
J.L. Poulsen ◽  
A.E. Olesen ◽  
C. Brock ◽  
T.H. Sandberg ◽  
...  

AbstractAimsTo employ a human experimental model of opioid-induced bowel dysfunction (OIBD) in healthy volunteers, and evaluate the impact of opioid treatment compared to placebo on gastrointestinal (GI) symptoms and motility, assessed by questionnaires and regional GI transit times.MethodsTwenty-five healthy males were randomly assigned to oxycodone or placebo for five days in a double-blind, crossover design. Adverse GI effects were measured with bowel function index, gastrointestinal symptom rating scale, patient assessment of constipation symptoms questionnaire, and bristol stool form scale. Regional GI transit times were determined using the 3D-Transit system and segmental colonic transit times were determined using a custom Matlab® graphical user interface.ResultsGI symptom scores increased significantly across all applied questionnaires during opioid treatment. Oxycodone increased median total GI transit time from 22.2 to 43.9 h (P< 0.01), segmental transit times in the cecum and ascending colon from 5.7 to 9.9 h (P<0.05), rectosigmoid transit time from 2.7 to 9.0 h (P<0.05), and colorectal transit time from 18.6 to 38.6 h (P<0.01). No association between questionnaire scores and segmental transit times were detected.ConclusionsSelf-assessed adverse GI effects and increased GI transit times in different segments were induced during oxycodone treatment. This detailed information about segmental changes in motility has great potential for future interventional head-to-head trials of different laxative regimes for prevention and treatment of OIBD.


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 7 (5) ◽  
Author(s):  
Giulienny Maria Antunes Gonçalves ◽  
Eduardo Euzieres Granzotto ◽  
Renato Mitsunori Nisihara ◽  
Jan Pawel Andrade Pachnicki ◽  
Lucas Marin Dall’Stella, ◽  
...  

Overview and Aims: Identify patients with surgically confirmed endometriosis and with gastrointestinal symptomatology by assessing whether there is clinical improvement of these from the adoption of gluten-free diet (GFD). Study design: They were invited to participate in the study by the researchers through telephone calls and instant messaging applications after selection in the clinics of attending physicians. Population: Through the GSRS (Gastrointestinal Symptom Rating Scale) questionnaire, the relationship of GFD adherence to symptomatology attenuation and benefit in the quality of life of 48 patients was analyzed. Methods: Inclusion criteria: female patients with surgical confirmation of endometriosis who agreed to participate in the study in accordance with the Informed Consent Form (ICF). Exclusion criteria: patients who already performed GFD, patients diagnosed with celiac disease, gluten allergy or non-celiac sensitivity to gluten, presence of gastrointestinal comorbidities, severe diseases or cognitive alterations that prevented the study from being performed. The patients who obtained the top 20 scores were invited to adopt GFD for one month, among those selected, only 12 proposed to participate in the diet. However, three of these presented personal complications that prevented the continuation of the same. After this period, a new questionnaire was applied to measure the impact of the diet on quality of life. Results: Nine patients finished the proposed period for the diet, with the average score obtained in the pre-diet questionnaire reducing from 57.2 to 36 in the post-diet. Conclusion: There was an improvement in gastrointestinal complaints of most patients and consequently in quality of life with GFD.


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.


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