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BACKGROUND:

MicroRNAs (miRNAs) are important post-transcriptional regulators. Altered expression of miRNAs has recently demonstrated association with human ulcerative colitis (UC). In this study, we attempted to elucidate the roles of miR-126 in the pathogenesis of UC.

METHODS:

Expression of miR-126, miR-21, miR-375 and the potential targets NF-κB inhibitor alpha (IκBα, IKBA or NFKBIA), Polo-like kinase 2 (PLK2) and v-Crk sarcoma virus CT10 oncogene homolog (CRK) were assessed in 52 colonic biopsies from patients with active UC, inactive UC, irritable bowel syndrome (IBS) and from healthy subjects by quantitative RT-PCR and immunofluorescence analyses. Regulation of gene expression by miR-126 was assessed using luciferase reporter construct assays and specific miRNA mimic transfection.

RESULTS:

We found that the expression of miR-126 and miR-21 were significantly increased in active UC group compared to the inactive UC, IBS and healthy control groups (P<0.05). In contrast, the expression of IKBA mRNA and protein was remarkably decreased in the active UC group compared with the other three groups (P<0.05). The expression of miR-126 and IKBA mRNA were inversely correlated in active UC patients (P<0.05). However the expression of miR-375, PLK2 and CRK showed no difference between each group. Furthermore, we demonstrate that endogenous miR-126 and exogenous miR-126 mimic can inhibit IκBα expression. Finally, mutating the miR-126 binding site of the IKBA 3'-UTR reporter construct restored reporter gene expression.

CONCLUSION:

miR-126 may play roles in UC inflammatory activity by down-regulating the expression of IKBA, an important inhibitor of NF-κB signaling pathway.

Introduction: This pilot, randomized controlled trial aimed to evaluate the usability, among adolescents and young adults (AYAs) with ulcerative colitis (UC), of a web-based tool (‘iBDecide’) designed to facilitate shared decision making (SDM). Methods: AYAs with UC (n = 35) were randomized to intervention (iBDecide, n = 14) and control (n = 12) arms before a scheduled clinic visit. We measured the usability of iBDecide, SDM, preferred decision-making style, decision conflict and intervention use. Results: Participants in the intervention group found iBDecide easy to use and agreed that it made them feel ready to participate in decision making and that they would use it to prepare for appointments. There were 130 visits to iBDecide, lasting on average 3 min, 41 s. The medication and nutrition trackers were among the most-viewed pages. Pages specifically designed to facilitate SDM were viewed only four times. Across groups, too few participants reported making decisions during clinic visits for decision-related measures to be reported. Conclusions: This pilot trial provides evidence for the usability of iBDecide and guidance for developing a larger-scale trial of a combined web-based and in-clinic SDM intervention. Overall, iBDecide shows promise in engaging AYAs with UC in SDM and condition management. Patient or Public Contribution: Patients, specifically AYAs with UC, and healthcare providers were involved in the design of this study's intervention, iBDecide. Additionally, the research team, from study conception to manuscript writing, included a young adult with inflammatory bowel disease. Clinical Trial Registration: This study was registered at clinicaltrials.gov (NCT04207008). © 2022 The Authors. Health Expectations published by John Wiley & Sons Ltd.

A relationship between ulcerative colitis (UC) and diet has been shown in epidemiological and experimental studies. In a 6-month, open-label, randomized, placebo-controlled trial, adult UC patients in clinical remission were randomized to either an "Anti-inflammatory Diet (AID)" or "Canada's Food Guide (CFG)". Menu plans in the AID were designed to increase the dietary intake of dietary fiber, probiotics, antioxidants, and omega-3 fatty acids and to decrease the intake of red meat, processed meat, and added sugar. Stool was collected for fecal calprotectin (FCP) and microbial analysis. Metabolomic analysis was performed on urine, serum, and stool samples at the baseline and study endpoint. In this study, 53 patients were randomized. Five (19.2%) patients in the AID and 8 (29.6%) patients in the CFG experienced a clinical relapse. The subclinical response to the intervention (defined as FCP < 150 µg/g at the endpoint) was significantly higher in the AID group (69.2 vs. 37.0%, p = 0.02). The patients in the AID group had an increased intake of zinc, phosphorus, selenium, yogurt, and seafood versus the control group. Adherence to the AID was associated with significant changes in the metabolome, with decreased fecal acetone and xanthine levels along with increased fecal taurine and urinary carnosine and p-hydroxybenzoic acid levels. The AID subjects also had increases in fecal Bifidobacteriaceae, Lachnospiraceae, and Ruminococcaceae. In this study, we found thatdietary modifications involving the increased intake of anti-inflammatory foods combined with a decreased intake of pro-inflammatory foods were associated with metabolic and microbial changes in UC patients in clinical remission and were effective in preventing subclinical inflammation.

Objectives: To determine the benefits of Lactobacillus rhamnosus GG (LGG) in an extensively hydrolyzed casein formula (EHCF) in improving hematochezia and fecal calprotectin over EHCF alone. Study design: Fecal calprotectin was compared in 30 infants with hematochezia and 4 weeks after milk elimination with that of a healthy group. We also compared fecal calprotectin and hematochezia on 26 formula-fed infants randomly assigned to EHCF with LGG (Nutramigen LGG) (EHCF + LGG) or without (Nutramigen) (EHCF - LGG) and on 4 breastfed infants whose mothers eliminated dairy. Results: Fecal calprotectin in those with hematochezia was significantly higher than in comparisons (mean ± SD 325.89 ± 152.31 vs 131.97 ± 37.98 μg/g stool, t = 6.79, P < .0001). At 4 weeks, fecal calprotectin decreased to 50% of baseline but was still significantly higher than in comparisons (157.5 ± 149.13 vs 93.72 ± 36.65 μg/g, P = .03). Fecal calprotectin mean decrease was significantly larger among EHCF + LGG compared with EHCF - LGG (-214.5 ± 107.93 vs -112.7 ± 105.27 μg/g, t = 2.43, P = .02). At 4 weeks, none of the EHCF + LGG had blood in stools, and 5/14 on EHCF - LGG did (P = .002). Conclusion: Fecal calprotectin is elevated in infants with hematochezia and possible allergic colitis. EHCF + LGG resulted in significant improvement of hematochezia and fecal calprotectin compared with the EHCF alone. © 2010 Mosby, Inc. All rights reserved.

BACKGROUND:

A substantial percentage of patients with ulcerative colitis (UC) have irritable bowel syndrome- (IBS-) like symptoms despite adequate treatment and endoscopic remission. In this study, we evaluated the clinical efficacy of probiotic therapy for residual IBS-like symptoms in patients with UC in endoscopic remission.

METHODS:

We conducted a multicenter, observational study between April 2018 and December 2020 across two university hospitals in Korea. Patients with UC whose IBS-like symptoms persisted during endoscopic remission were included in this study. Endoscopic remission was defined as a Mayo endoscopic score ≤ 1, and IBS-like symptoms were defined as those meeting the ROME-IV diagnostic criteria. A Biotop capsule® (Lactobacillus acidophilus, 75 mg; Clostridium butyricum TO-A, 25 mg; Bacillus mesentericus TO-A, 25 mg; and Streptococcus faecalis T-110, 5 mg) was administered three times daily for one month. All patients completed bowel-related symptom questionnaires and short inflammatory bowel disease questionnaires (SIBDQs) at the start and end of the 4-week treatment period.

RESULTS:

A total of 43 patients were enrolled and analyzed. Statistically significant improvements from baseline were observed at the end of the 4-week treatment. The total SIBDQ score improved from 50.6 to 53.6 (P = 0.005). SIBDQ scores of bowel function (P = 0.018), systemic function (P = 0.040), and social function (P = 0.005) improved. Stool frequency and Bristol stool scale scores improved after probiotic therapy (P < 0.05).

CONCLUSION:

This study showed that probiotic administration improved bowel-related symptoms and quality of life in patients with UC whose IBS-like symptoms persisted during endoscopic remission. As this is an observational study and has no placebo-controlled arm, further prospective randomized controlled trials are needed to confirm these results.

Background: Suppressor of Tumorigenicity 2 (ST2) is an IL33 receptor detected in the mucosa and serum of ulcerative colitis (UC) patients. We evaluated soluble ST2 (sST2) as a surrogate biomarker of disease outcome and therapeutic response, in moderate-to-severe UC patients treated with golimumab. Methods: We conducted an open-label single-arm multicentre prospective study. At screening/baseline, week 6 (W6) and week 16 (W16), clinical and endoscopic activity (total Mayo score), histologic activity (Geboes index) and biomarkers were evaluated. Results: From 38 patients, 34 (89.5%) completed W6 and 29 (76.3%) completed W16. Mean age (±SD) was 34.6 ± 12.6 years; 55.9% were female. At W16, 62.1% achieved clinical response. Patients with endoscopic activity at W6 (n = 20) had higher baseline sST2 (median, 24.5 versus 18.7 ng/ml, p = 0.026) and no decrease from baseline (median change, 0.8 versus −2.7, p = 0.029). At W6, sST2 levels correlated with endoscopic activity (rs = 0.45, p = 0.007) but not with histological activity (rs = 0.25, p = 0.151). The best cut-offs for endoscopic activity were sST2 = 16.9 ng/ml (sensitivity = 85%; specificity = 71%) and faecal calprotectin (FC) = 353 μg/g (sensitivity = 90%, specificity = 67%). Patients with histological activity at W6 (n = 27) had higher baseline ST2 levels (median, 23.0 versus 13.7 ng/ml, p = 0.035). sST2 did not correlate with FC or serum C-reactive protein. FC levels correlated with histological activity and baseline FC were higher when Geboes ⩾3.1 at W6. Conclusions: sST2 may be a surrogate biomarker of UC activity and therapeutic response as it correlates with endoscopic and clinical activity at W6 of golimumab treatment, and subjects with endoscopic and histological activity at W6 had higher baseline ST2 levels.

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BACKGROUND:

A gap remains in documenting the impact of anti-tumor necrosis factor therapy on disease burden in ulcerative colitis (UC) patients treated in a real-world setting. The use of patient-reported outcomes (PROs) has been discussed as a primary endpoint in the context of the FDA PRO Guidance, for labelling purposes. Specifically, the efficacy and safety of adalimumab have been demonstrated in pivotal trials; however, data are needed to understand how clinical results translate into improvements in key aspects of the daily lives of UC patients, such as symptoms, health-related quality of life (HRQoL), and disability.

AIM:

To assess real-world effectiveness of adalimumab on PRO measures in patients with moderate-to-severe UC.

METHODS:

UCanADA was a single arm, prospective, 1-year multicenter Canadian post-marketing observational study in which multiple PRO questionnaires were completed-with psychologic distress/depression symptoms as the primary endpoint-by patients with moderate-to-severe UC. Assessments were performed during patients' routine care visit schedule, which was at the initiation of adalimumab (baseline), after induction (approximately 8 wk), and 52 wk after baseline. Additional optional assessments between weeks 8 and 52 were collected at least once but no more than two times during this period. Serious safety events and per-protocol adverse events were collected.

RESULTS:

From 23 Canadian centres, 100 patients were enrolled and 48 completed the study. Measured with the Patient Health Questionnaire-9 items at week 52, 61.5% (40/65) [95% confidence interval (CI): 49.7%-73.4%] of the patients improved in psychologic distress/depression symptoms, which was slightly higher in completers [65.9% (29/44); 95%CI: 51.9%-79.9%)]. At week 52, clinical response and clinical remission were achieved respectively by 65.7% (44/73) and 47.8% (32/73) of the patients. The odds of improving depressive symptoms for those achieving a clinical remission at week 52 was 7.94 higher compared with those not achieving a clinical remission (CI: 1.42, 44.41; P = 0.018). Significant changes from baseline to weeks 8 and 52 were observed in disability, HRQoL, and fatigue. Meaningful improvement was reported in work impairment.

CONCLUSION:

At week 52, over 60% of the UCanADA patients had depressive symptoms significantly reduced, as well as HRQoL, fatigue symptoms, and work impairment improved. No new safety signals were detected.