Prebiotic galactooligosaccharide supplementation in adults with ulcerative colitis:Exploring the impact on peripheral blood gene expression, gut microbiota, and clinical symptoms

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

Validation and Investigation of the Operating Characteristics of the Ulcerative Colitis Endoscopic Index of Severity

BACKGROUND: The Ulcerative Colitis Endoscopic Index of Severity (UCEIS) is a novel instrument to evaluate endoscopic disease activity. It has been demonstrated to outperform the more widely used Mayo endoscopic score (MES) in predicting long-term prognosis, including the need for colectomy. Despite its potential benefits, many clinicians still prefer to use MES because its operating characteristics are better defined and its grades are more readily applicable to clinical decision-making. The aims of our study were to quantify the UCEIS cutoff most closely associated with the need for treatment escalation and to perform a validation exercise using MES and clinical, biochemical, and histological measures of disease activity. METHODS: Endoscopies performed in UC patients between November 2016 and January 2018 were retrospectively reviewed. Agreement between the UCEIS and MES was quantified using Kappa (κ) statistics. A UCEIS cutoff for treatment escalation was calculated using chi-square, receiver operating characteristic curve, and area under the curve (AUC) analyses. The Pearson correlation coefficient was used to compare linear relationships between UCEIS and clinical (Simple Clinical Colitis Activity Index [SCCAI]), biochemical (C-reactive protein [CRP]), and histological (Nancy Histological Index [NHI]) activity. RESULTS: Two hundred one (56%) procedures documented both UCEIS and MES, demonstrating substantial agreement (κ = 0.713; P < 0.001). Treatment was escalated after 199 (56%) procedures. Receiver operating characteristic curve analysis of need for treatment escalation showed the highest sensitivity and specificity for UCEIS ≥4 (0.80 and 0.93, respectively; AUC, 0.93). Of 170 patients with a UCEIS ≥4, treatment was escalated in 159 (94%), but not for 11 (6%). Of 185 patients with a UCEIS ≤3, 40 (22%) were escalated, whereas 145 (78%) were not (P < 0.001). UCEIS correlated strongly with NHI (0.723; P < 0.001), moderately with SCCAI (0.671; P < 0.001), and weakly with CRP (0.279; P < 0.001). CONCLUSIONS: A UCEIS ≥4 was significantly associated with treatment escalation. This cutoff could therefore be used to support clinical decision-making based on endoscopic findings. Strong and moderate correlations were found between UCEIS and histological and clinical disease activity, respectively, whereas a weak correlation was found with CRP. 10.1093/ibd/izy325_Video_1 izy325.video1 5849933952001

Assessment, endoscopy, and treatment in patients with acute severe ulcerative colitis during the COVID-19 pandemic (PROTECT-ASUC): a multicentre, observational, case-control study

BackgroundThere is a paucity of evidence to support safe and effective management of patients with acute severe ulcerative colitis during the COVID-19 pandemic. We sought to identify alterations to established conventional evidence-based management of acute severe ulcerative colitis during the early COVID-19 pandemic, the effect on outcomes, and any associations with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe COVID-19 outcomes. MethodsThe PROTECT-ASUC study was a multicentre, observational, case-control study in 60 acute secondary care hospitals throughout the UK. We included adults (≥18 years) with either ulcerative colitis or inflammatory bowel disease unclassified, who presented with acute severe ulcerative colitis and fulfilled the Truelove and Witts criteria. Cases and controls were identified as either admitted or managed in emergency ambulatory care settings between March 1, 2020, and June 30, 2020 (COVID-19 pandemic period cohort), or between Jan 1, 2019, and June 30, 2019 (historical control cohort), respectively. The primary outcome was the proportion of patients with acute severe ulcerative colitis receiving rescue therapy (including primary induction) or colectomy. The study is registered with ClinicalTrials.gov, NCT04411784. FindingsWe included 782 patients (398 in the pandemic period cohort and 384 in the historical control cohort) who met the Truelove and Witts criteria for acute severe ulcerative colitis. The proportion of patients receiving rescue therapy (including primary induction) or surgery was higher during the pandemic period than in the historical period (217 [55%] of 393 patients vs 159 [42%] of 380 patients; p=0·00024) and the time to rescue therapy was shorter in the pandemic cohort than in the historical cohort (p=0·0026). This difference was driven by a greater use of rescue and primary induction therapies with biologicals, ciclosporin, or tofacitinib in the COVID-19 pandemic period cohort than in the historical control period cohort (177 [46%] of 387 patients in the COVID-19 cohort vs 134 [36%] of 373 patients in the historical cohort; p=0·0064). During the pandemic, more patients received ambulatory (outpatient) intravenous steroids (51 [13%] of 385 patients vs 19 [5%] of 360 patients; p=0·00023). Fewer patients received thiopurines (29 [7%] of 398 patients vs 46 [12%] of 384; p=0·029) and 5-aminosalicylic acids (67 [17%] of 398 patients vs 98 [26%] of 384; p=0·0037) during the pandemic than in the historical control period. Colectomy rates were similar between the pandemic and historical control groups (64 [16%] of 389 vs 50 [13%] of 375; p=0·26); however, laparoscopic surgery was less frequently performed during the pandemic period (34 [53%] of 64] vs 38 [76%] of 50; p=0·018). Five (2%) of 253 patients tested positive for SARS-CoV-2 during hospital treatment. Two (2%) of 103 patients re-tested for SARS-CoV-2 during the 3-month follow-up were positive 5 days and 12 days, respectively, after discharge from index admission. Both recovered without serious outcomes. InterpretationThe COVID-19 pandemic altered practice patterns of gastroenterologists and colorectal surgeons in the management of acute severe ulcerative colitis but was associated with similar outcomes to a historical cohort. Despite continued use of high-dose corticosteroids and biologicals, the incidence of COVID-19 within 3 months was low and not associated with adverse COVID-19 outcomes