Disease Activity In Colitis Research Articles

Diagnostic utility, disease activity, and disease phenotype correlation of serum ASCA, pANCA, and PR3-ANCA in pediatric inflammatory bowel disease

ObjectiveThis study aimed to evaluate the diagnostic utility, disease activity, and phenotypic association of serum anti-Saccharomyces cerevisiae antibody (ASCA), perinuclear anti-neutrophil cytoplasmic antibody (pANCA), PR3-ANCA, and MPO-ANCA in pediatric patients with inflammatory bowel disease (IBD). MethodsPediatric patients diagnosed with IBD were recruited and classified as Crohn's disease (CD), ulcerative colitis (UC), and IBD-unclassified (IBD-U) through full investigation. The Paris classification was used to evaluate disease phenotypes of pediatric CD and UC. ResultsIn all, 229 pediatric patients with IBD (CD 147, UC 53, IBD-U 29) were included. The ASCA IgG seropositivity significantly differed among the three groups (CD 75.4%, UC 17.5%, and IBD-U 60.0%; p < 0.001). PR3-ANCA positive rates were the highest in UC (24.0%), followed by IBD-U (17.6%), and none in CD (p = 0.002); pANCA-positive rates were higher in IBD-U (33.6%), followed by UC (28.0%) than in CD (1.4%) (p < 0.001). Regarding disease phenotype, perianal disease revealed higher serum ASCA IgG titers (median 36.7 U/mL in P1 vs. 25.2 U/mL in P0, p = 0.019). Serum ASCA IgG and IgA cutoff values to distinguish CD were 32.7 (U/mL) and 11.9 (U/mL), respectively, with a specificity of 80.0%. ConclusionSerological biomarkers of ASCA IgG and IgA were effective for differentiating CD in pediatric IBD patients, and serum pANCA and PR3-ANCA, but not MPO-ANCA, were effective in distinguishing UC and IBD-U. Furthermore, measuring serological titers of ASCA IgG and IgA may help differentiate CD and evaluate the disease activity and phenotype of pediatric IBD in practice.

Biomarkers for Monitoring of Changes in Disease Activity in Ulcerative Colitis.

In recent years, various biomarkers of ulcerative colitis (UC) have emerged; however, few studies have simultaneously examined the utility of multiple biomarkers for monitoring disease activity. Additionally, serum leucine-rich alpha-2 glycoprotein (LRG), a new biomarker, may show a blunt response to anti-TNF antibody therapy. This prospective study explored effective biomarkers that could monitor disease activity changes in patients with UC. In addition, we examined the effect of anti-TNF antibody therapy on changes in LRG. Blood and stool samples were collected twice from patients with UC: at baseline and at least 8 weeks later. Changes in serum LRG, interleukin (IL)-6, prealbumin (pre-Alb), high-sensitivity C-reactive protein (hs-CRP), CRP, and fecal calprotectin (FC) were measured and correlated with changes in disease activity. The relationship between anti-TNF antibody therapy and LRG levels was also examined in patients with the same disease activity. Forty-eight patients with UC (96 samples) were analyzed. ΔLRG and ΔIL-6 correlated strongly with the change in the partial Mayo (pMayo) score between the two time points (ΔpMayo) (r = 0.686, 0.635, respectively). In contrast, FC and IL-6 were particularly accurate predictors of clinical remission, and their area under the curves (AUCs) were significantly higher than that of CRP (AUC: 0.81, 0.76 vs. 0.50; p = 0.001, 0.005). No association was found between the administration of anti-TNF antibody preparations and the LRG values. Correlations were found between changes in UC disease activity and LRG, IL-6, pre-Alb, hs-CRP, CRP, and FC. LRG reflects disease activity during anti-TNF antibody therapy.

Evaluation of Disease Activity in Inflammatory Bowel Disease: Diagnostic Tools in the Assessment of Histological Healing.

Inflammatory bowel disease (IBD) comprises two types of chronic intestinal disorders: Crohn's disease and ulcerative colitis. In long-standing ulcerative colitis disease activity, histological persistent inflammation has been linked to an increased risk of relapse, and long-term corticosteroid use, even when endoscopic remission is reached. In Crohn's disease, the discontinuous nature of lesions and transmural inflammation have limited the standardized histological assessment. The current evidence from research proposes that besides clinical and endoscopic healing, the achievement of histological healing constitutes an endpoint to assess disease activity and remission in IBD patients concerning better long-term disease outcomes. Histological alterations may persist even in the absence of endoscopic lesions. For these reasons, new advanced techniques promise to revolutionize the field of IBD by improving the endoscopic and histologic assessment, disease characterization, and ultimately patient care, with an established role in daily practice for objective assessment of lesions. This review outlines the importance of including microscopic evaluation in IBD, highlighting the clinical benefits of a deep state of disease remission using validated diagnostic methods and scoring systems for daily clinical practice.

Long-term risk of arrhythmias in patients with inflammatory bowel disease: A population-based, sibling-controlled cohort study.

Although previous evidence has suggested an increased risk of cardiovascular disease (CVD) in patients with inflammatory bowel disease (IBD), its association with arrhythmias is inconclusive. In this study, we aimed to explore the long-term risk of arrhythmias in patients with IBD. Through a nationwide histopathology cohort, we identified patients with biopsy-confirmed IBD in Sweden during 1969 to 2017, including Crohn's disease (CD: n = 24,954; median age at diagnosis: 38.4 years; female: 52.2%), ulcerative colitis (UC: n = 46,856; 42.1 years; 46.3%), and IBD-unclassified (IBD-U: n = 12,067; 43.8 years; 49.6%), as well as their matched reference individuals and IBD-free full siblings. Outcomes included overall and specific arrhythmias (e.g., atrial fibrillation/flutter, bradyarrhythmias, other supraventricular arrhythmias, and ventricular arrhythmias/cardiac arrest). Flexible parametric survival models estimated hazard ratios (aHR) with 95% confidence intervals (95% CIs), after adjustment for birth year, sex, county of residence, calendar year, country of birth, educational attainment, number of healthcare visits, and cardiovascular-related comorbidities. Over a median of approximately 10 years of follow-up, 1,904 (7.6%) patients with CD, 4,154 (8.9%) patients with UC, and 990 (8.2%) patients with IBD-U developed arrhythmias, compared with 6.7%, 7.5%, and 6.0% in reference individuals, respectively. Compared with reference individuals, overall arrhythmias were increased in patients with CD [54.6 versus 46.1 per 10,000 person-years; aHR = 1.15 (95% CI [1.09, 1.21], P < 0.001)], patients with UC [64.7 versus 53.3 per 10,000 person-years; aHR = 1.14 (95% CI [1.10, 1.18], P < 0.001)], and patients with IBD-U [78.1 versus 53.5 per 10,000 person-years; aHR = 1.30 (95% CI [1.20, 1.41], P < 0.001)]. The increased risk persisted 25 years after diagnosis, corresponding to 1 extra arrhythmia case per 80 CD, 58 UC, and 29 IBD-U cases over the same period. Patients with IBD also had a significantly increased risk of specific arrhythmias, except for bradyarrhythmias. Sibling comparison analyses confirmed the main findings. Study limitations include lack of clinical data to define IBD activity, not considering the potential role of IBD medications and disease activity, and the potential residual confounding from unmeasured factors for arrhythmias. In this study, we observed that patients with IBD were at an increased risk of developing arrhythmias. The excess risk persisted even 25 years after IBD diagnosis. Our findings indicate a need for awareness of this excess risk among healthcare professionals.

Deep Learning Models Capture Histological Disease Activity in Crohn's Disease and Ulcerative Colitis with High Fidelity.

Histological disease activity in inflammatory bowel disease [IBD] is associated with clinical outcomes and is an important endpoint in drug development. We developed deep learning models for automating histological assessments in IBD. Histology images of intestinal mucosa from phase 2 and phase 3 clinical trials in Crohn's disease [CD] and ulcerative colitis [UC] were used to train artificial intelligence [AI] models to predict the Global Histology Activity Score [GHAS] for CD and Geboes histopathology score for UC. Three AI methods were compared. AI models were evaluated on held-back testing sets, and model predictions were compared against an expert central reader and five independent pathologists. The model based on multiple instance learning and the attention mechanism [SA-AbMILP] demonstrated the best performance among competing models. AI-modelled GHAS and Geboes subgrades matched central readings with moderate to substantial agreement, with accuracies ranging from 65% to 89%. Furthermore, the model was able to distinguish the presence and absence of pathology across four selected histological features, with accuracies for colon in both CD and UC ranging from 87% to 94% and for CD ileum ranging from 76% to 83%. For both CD and UC and across anatomical compartments [ileum and colon] in CD, comparable accuracies against central readings were found between the model-assigned scores and scores by an independent set of pathologists. Deep learning models based upon GHAS and Geboes scoring systems were effective at distinguishing between the presence and absence of IBD microscopic disease activity.

Growth hormone use in pediatric inflammatory bowel disease.

Impaired linear growth is a known complication of pediatric inflammatory bowel disease (IBD), but theuse of growth hormone (GH) in this population is not well-described. The primary aim of this study is to determine whether growth hormone use in pediatric IBD leads to improved height outcomes. This was a retrospective chart review of patients with IBD aged 0-21 years followed at a single center between 2018 and 2021 treated with at least 1 year of GH. Records collected included demographics, IBD phenotype, IBD disease activity scores, medications, weight z-score, height z-score, bone age, and details of GH therapy including testing for GH deficiency. The primary outcome measure was change in height z-score after 1 year of GH treatment. Forty-six patients were identified and 18 were excluded. Of the 28 patients included (7 female; 25.0 %), 26 (92.9 %) had a diagnosis of Crohn's disease (CD) and 2 (7.1 %) had ulcerative colitis (UC). The mean (SD) age at GH initiation was 9.6 (3.4) years. Among all participants, there was a significant mean difference in height z-score from baseline to 1 year on therapy (-2.25 vs.-1.50, respectively; difference, 0.75; 95 % CI, 0.56 to 0.94; p<0.001). Among the 19 subjects thatcompleted GH therapy there was a significant mean difference between baseline and final height z-scores (-2.41vs.-0.77, respectively; difference, 1.64; 95 % CI, 1.30 to 1.98; p<0.001). GH use was associated with improved height outcomes. The pediatric IBD patients in this cohort had significant improvements in height z-scores both after one year on therapy and at completion of GH therapy.

Fundamental role for the creatine kinase pathway in protection from murine colitis

Inflammatory diseases of the digestive tract, including inflammatory bowel disease, cause metabolic stress within mucosal tissue. Creatine is a key energetic regulator. We previously reported a loss of creatine kinases (CKs) and the creatine transporter expression in inflammatory bowel disease patient intestinal biopsy samples and that creatine supplementation was protective in a dextran sulfate sodium (DSS) colitis mouse model. In the present studies, we evaluated the role of CK loss in active inflammation using the DSS colitis model. Mice lacking expression of CK brain type/CK mitochondrial form (CKdKO) showed increased susceptibility to DSS colitis (weight loss, disease activity, permeability, colon length, and histology). In a broad cytokine profiling, CKdKO mice expressed near absent interferon gamma (IFN-γ) levels. We identified losses in IFN-γ production from CD4+ and CD8+ T cells isolated from CKdKO mice. Addback of IFN-γ during DSS treatment resulted in partial protection for CKdKO mice. Extensions of these studies identified basal stabilization of the transcription factor hypoxia-inducible factor in CKdKO splenocytes and pharmacological stabilization of hypoxia-inducible factor resulted in reduced IFN-γ production by control splenocytes. Thus, the loss of IFN-γ production by CD4+ and CD8+ T cells in CKdKO mice resulted in increased colitis susceptibility and indicates that CK is protective in active mucosal inflammation.

High prevalence of Mucosa-Associated extended-spectrum β-Lactamase-producing Escherichia coli and Klebsiella pneumoniae among Iranain patients with inflammatory bowel disease (IBD)

BackgroundSeveral pieces of evidence suggest that certain pathobionts belonging to Enterobacterales are associated with the development and progression of inflammatory bowel diseases (IBD). Extended-spectrum β-lactamases (ESBLs) ESBLs are frequently found in the Enterobacterales members, particularly in Escherichia coli and Klebsiella spp., and might trigger antibiotic-induced perturbations of the intestinal microbiota and led to more severe disease activity in IBD. Therefore, the severity of IBD could be influenced by ESBL-producing Enterobacterales, and hence, this study aimed to investigate the presence of ESBLs and carbapenemases among mucosa-associated E. coli and Klebsiella pneumoniae isolated from colonic biopsies of Iranian patients with IBD.MethodsIn this cross-sectional study, E. coli and K. pneumoniae were isolated from inflamed ileum and/or colon tissue of patients with IBD, including Ulcerative colitis (UC) and Crohn’s disease (CD), during colonoscopy. Demographic data and clinical characteristics were recorded, and UC and CD disease activity and extent were evaluated according to the full Mayo score and Crohn’s disease activity index (CDAI), respectively. Phenotypic and molecular detection of ESBL- and carbapenemase-producing E. coli and Klebsiella pneumoniae were carried out. Disease activity and other clinical and microbial features were compared in patients with and without gut colonization with ESBL producers.ResultsA total of 83 IBD patients, including 67 UC and 16 CD, were enrolled in the initial analysis. Intestinal colonization with ESBL-producing E. coli and/or Klebsiella pneumoniae was found in 37 (55.2%) of UC and 9 (56.2%) of DC patients – mostly harbored E. coli containing the blaCTX−M and blaTEM genes. UC patients with intestinal colonization with ESBL-producers had more severe disease compared with patients without colonization. Moreover, 10.2% of tested E. coli and 34.8% of K. pneumoniea were recognized as potential carbapenemase producers.ConclusionIntestinal colonization with ESBL producers could arise disease activity in IBD patients. Further large-scale case-control studies should be performed to investigate the possible confounding factors that could contribute to this outcome.

Medical Cannabis Use Patterns and Adverse Effects in Inflammatory Bowel Disease.

To investigate medical cannabis (MC) use patterns and adverse effects in patients with inflammatory bowel disease (IBD). MC is now legal in many states. Although previous studies suggest improvement in disease activity among IBD patients using MC, use patterns and adverse effects are unclear. A cross-sectional anonymous survey was conducted (October 23, 2020 to January 24, 2021) among patients accessing MC dispensaries in New York and Minnesota. Eligibility criteria: age 18 years or older, selfreported IBD diagnosis, MC dispensary purchase. Survey questions included IBD characteristics, MC and healthcare utilization, and MC effects/adverse events. Participant characteristics were analyzed with descriptive statistics. Utilization patterns and symptoms before and after MC use were compared using the Stuart Maxwell test. Of 236 respondents, overall IBD disease activity was mild-to-moderate. Most respondents (61.0%) took a biological. Median frequency of MC use was at least once within the past week. Most respondents used products with high Δ9-tetrahydrocannabinol content (87.5%) through vape pens/cartridges (78.6%). Respondents reported fewer emergency room visits in the 12 months after versus before MC use (35.2 vs 41.5%, P <0.01) and less impact of symptoms on daily life. Most respondents reported euphoria with MC use (75.4%). The other common side effects were feeling drowsy, groggy, or with memory lapses (4.2%), dry mouth/eyes (3.4%), and anxiety/depression or paranoia (3.4%). Few respondents reported MC diversion (1.3%). MC users with IBD perceive symptom benefits and report decreased emergency room visits without serious adverse effects. Further studies are needed to confirm these results with objective measures of healthcare utilization and disease activity.

Long-term follow-up of the red density pilot trial: a basis for long-term prediction of sustained clinical remission in ulcerative colitis?

Red density (RD) technology is an automated operator-independent endoscopic scoring system for disease activity in ulcerative colitis (UC). In this retrospective analysis we aimed to assess the predictive value of the RD sore for sustained clinical remission. All 39 patients from the RD pilot trial were evaluated for clinical outcome in a 5-year period. The highest RD score was considered for Receiver operating characteristic (ROC) analysis to determine the cut-off of the RD for the composite endpoint of treatment failure (defined as mortality, colectomy, hospitalizations, flares and UC therapy changes). Statistical significance was considered P < 0.05. Reassessment of the RD score was possible in 36 patients. The composite endpoint was reached in 17 of 39 patients. ROC analysis for clinical remission showed a RD cut-off of 65, area under the ROC was 0.68, sensitivity of 0.71, and a specificity of 0.63. A RD score of ≥ 65 demonstrated a statistically non-significant increase in composite endpoint (hazard ratio 0.49 (95% confidence interval 0.1871-1.280); P = 0.1453). In conclusion, the RD score may be an independent predictor of clinical remission in patients with UC for the disease course up to 5 years, but results of the ongoing PROCEED-UC trial are to awaited for definite conclusions.

Polysaccharides from Tetrastigma Hemsleyanum Diels et Gilg ameliorated inflammatory bowel disease by rebuilding the intestinal mucosal barrier and inhibiting inflammation through the SCFA-GPR41/43 signaling pathway

In this study, the therapeutic effects of Tetrastigma hemsleyanum polysaccharide (THP) on inflammatory bowel disease (IBD) and its possible mechanisms were investigated based on the IBD mouse model induced by dextran sodium sulfate (DSS) and the lipopolysaccharide (LPS)-stimulated Caco-2 cell model. THP significantly alleviated the signs and symptoms of DSS-induced IBD mice, including the reduced weight, shortened colonic length, and increased colitis disease activity index. In vivo, THP significantly reduced inflammatory cell infiltration and oxidative damage, promoted intestinal mucus secretion, and restored the integrity of the intestinal epithelial barrier and mucus barrier. Furthermore, THP reversed the changes in the intestinal flora of colonized mice and restored the levels of short-chain fatty acids (SCFAs) by increasing the abundance of potentially beneficial bacteria and increasing the abundance of butyrate-producing bacteria. In addition, THP upregulated the expression of G-protein-coupled receptors (GPR41 and GPR43) both in vivo and in vitro. In summary, the current investigation showed that THP effectively protected against intestinal inflammation and impairment in the intestinal barrier in the setting of DSS-induced IBD, possibly by regulating gut microbiota structure and corresponding SCFA metabolites, and the pathway of SCFAs action may be related to SCFA-GPR41/43 signaling pathway.

Association with controlling nutritional status score and disease activity of ulcerative colitis.

To explore the association between the controlling nutritional status (CONUT) score and disease activity in patients with ulcerative colitis (UC). This retrospective study enrolled patients with UC. Demographic, clinical and laboratory data were collected and compared. The CONUT score was obtained for each patient. The association between the CONUT score and laboratory parameters was analysed and the ability of the score to assess disease activity was evaluated. A total of 182 patients with UC were enrolled. Patients with active disease showed significantly increased inflammatory biomarkers and decreased nutritional biomarkers compared with patients in remission. Malnourished individuals had significantly elevated inflammatory biomarkers and significantly reduced haemoglobin, prealbumin and retinol-binding protein. The CONUT score was inversely correlated with haemoglobin, prealbumin, retinol-binding protein and was positively correlated with faecal calprotectin, C-reactive protein, erythrocyte sedimentation rate, neutrophil/lymphocyte ratio and platelet/lymphocyte ratio. The area under the receiver operating characteristic curve was 0.655 (95% confidence interval, 0.557-0.752). The optimal cut-off value was 1.5 points, with a sensitivity of 75.7% and a specificity of 50.0%. The CONUT score may evaluate the inflammatory response and nutritional status of UC patients, so it could be a potential biomarker to assess disease activity in UC.

The effect of selenium supplementation on disease activity and immune-inflammatory biomarkers in patients with mild-to-moderate ulcerative colitis: a randomized, double-blind, placebo-controlled clinical trial.

Selenium (Se) supplementation may help reduce inflammation and disease activity in ulcerative colitis (UC) patients. We investigated the therapeutic effects of Se administration in cases with mild-to-moderate active UC. A multicenter, double-blind, randomized clinical trial (RCT) was conducted on 100 cases with active mild-to-moderate UC. The patients were randomly allocated to be given an oral selenomethionine capsule (200 mcg/day, n = 50) or a placebo capsule (n = 50) for 10 weeks. The primary outcome was defined as disease activity via the Simple Clinical Colitis Activity Index (SCCAI), and secondary outcomes were measured at the end of the study. After 10 weeks, the SCCAI score's mean was reduced in the Se group (P < 0.001). At the end of the intervention, clinical improvement (decline of 3 ≥ score from baseline score) was observed in 19 patients (38%) of the Se group and 3 patients (6%) of the placebo group. The patients with clinical remission (defined as SCCAI ≤ 2) were assigned in the Se group (P = 0.014). The Se group's quality of life and Se serum levels were enhanced at the end of the study (P < 0/001). In the Se group, the mean concentration of interleukin-17 decreased (P < 0/001). However, the levels of interleukin-10 showed no considerable change between the two groups in the 10th week (P = 0.23). Se supplementation as add-on therapy with medical management induced remission and improved the quality of life in patients with active mild-to-moderate UC. IRCT20091114002709N51; 2020-04-13.

Development of a scoring system for predicting the severity of ulcerative colitis

Background and study aimsMonitoring disease activity in ulcerative colitis (UC) is critical in preventing long-term complications. This study aims to develop a scoring system using non-invasive indicators to predict endoscopic activities for ulcerative colitis (UC) patients. Patients and methodsAll enrolled patients with UC admitted to Shanghai Xinhua Hospital between June 2017 and January 2021 were enrolled, and their clinical data were retrospectively collected and a number of serological biomarkers concentrations were analyzed. Patients were categorized into mild and moderate-to-severe disease groups. Univariate and multivariate logistic regression was used to predict moderate-to-severe endoscopic activities, which were then incorporated into a nomogram to establish a prediction scoring model. ResultOverall, 231 patients were divided into a mild group (n = 111, 48.0%) and a moderate-to-severe group (n = 120, 52.0%). The following variables were independently associated with the disease severity and were subsequently included into the prediction model: Proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA), C-reactive protein (CRP), hemoglobin(Hb), IL-10, stool frequency ≥ 5 times/day and hematochezia. Incorporating these 6 factors, the nomogram showed good discrimination with C-index of 0.819 and reliable calibration. A scoring model was established with the area under the curve 0.818. Moreover, PR3-ANCA and CRP correlated with the duration of hospital stay. ConclusionWe developed a predictive model for endoscopic disease activities by using noninvasive factors based on PR3-ANCA, CRP, Hb, IL-10, stool frequency and hematochezia. This prediction model might assist clinicians in managing patients with UC.

Engineered calprotectin-sensing probiotics for IBD surveillance in humans

Inflammatory bowel disease (IBD) is a spectrum of autoimmune diseases affecting the gastrointestinal tract characterized by a relapsing and remitting course of gut mucosal inflammation. Disease flares can be difficult to predict, and the current practice of IBD disease activity surveillance through endoscopy is invasive and requires medical expertise. Recent advancements in synthetic biology raise the possibility that symbiotic microbes can be engineered to selectively detect disease biomarkers used in current clinical practice. Here, we introduce an engineered probiotic capable of detecting the clinical gold standard IBD biomarker, calprotectin, with sensitivity and specificity in IBD patients. Specifically, we identified a bacterial promoter in the probiotic strain Escherichia coli Nissle 1917 (EcN) which exhibits a specific expression increase in the presence of calprotectin. Using murine models of colitis, we show that the reporter signal is activated in vivo during transit of the GI tract following oral delivery. Furthermore, our engineered probiotic can successfully discriminate human patients with active IBD from those in remission and without IBD using patient stool samples, where the intensity of reporter signal quantitatively tracks with clinical laboratory-measured levels of calprotectin. Our pilot study sets the stage for probiotics that can be engineered to detect fecal calprotectin for precise noninvasive disease activity monitoring in IBD patients.

Biomarkers of ulcerative colitis disease activity CXCL1, CYP2R1, LPCAT1, and NEU4 and their relationship to immune infiltrates

The diagnosis and assessment of ulcerative colitis (UC) poses significant challenges, which may result in inadequate treatment and a poor prognosis for patients. This study aims to identify potential activity biomarkers for UC and investigate the role of infiltrating immune cells in the disease. To perform gene set enrichment analysis, we utilized the cluster profiler and ggplot2 packages. Kyoto encyclopedia of genes and genomes was used to analyze degenerate enrichment genes. Significant gene set enrichment was determined using the cluster profiler and ggplot2 packages. Additionally, quantitative PCR (qRT-PCR) was employed to validate the expression of each marker in the ulcerative colitis model. We identified 651 differentially expressed genes (DEGs) and further investigated potential UC activity biomarkers. Our analysis revealed that CXCL1 (AUC = 0.710), CYP2R1 (AUC = 0.863), LPCAT1 (AUC = 0.783), and NEU4 (AUC = 0.833) were promising activity markers for the diagnosis of UC. Using rat DSS model, we validated these markers through qRT-PCR, which showed statistically significant differences between UC and normal colon mucosa. Infiltrating immune cell analysis indicated that M1 macrophages, M2 macrophages, activated dendritic cells (DCs), and neutrophils played crucial roles in the occurrence and progression of UC. Moreover, the activity markers exhibited varying degrees of correlation with activated memory CD4 T cells, M0 macrophages, T follicular helper cells, memory B cells, and activated DCs. The potential diagnostic genes for UC activity, such as CXCL1, CYP2R1, LPCAT1, and NEU4, as well as the infiltration of immune cells, may contribute to the pathogenesis and progression of UC.

Association between body fat composition and disease duration, clinical activity, and intravenous corticosteroid-induced response in inflammatory bowel disease

BackgroundBody fat composition is believed to be associated with the progression, medical response, and prognosis of inflammatory bowel disease (IBD). Hence, we conducted this study to explore if fat metrics were associated with the disease activity of severe IBD and the response to intravenous corticosteroids (IVCS).MethodsWe included 69 patients with ulcerative colitis (UC) and 72 patients with Crohn's disease (CD) who had previously received IVCS during hospitalization. We quantified individual fat distribution using abdominal computed tomography slices. The correlations between fat parameters and disease activity were available with Spearman correlation analysis. The prediction model was developed using independent risk factors derived from multivariable logistic regression analysis. Model discrimination was evaluated leveraging the receiver operating characteristic curve. 1000 bootstrap resamples internally validated the model's prediction performance.ResultsNotable differences in age, nutritional status, serum cytomegalovirus replication, stool condition, and extraintestinal involvement between UC and CD patients were observed. UC subjects who responded to IVCS had higher subcutaneous adipose tissue index (SATI), visceral adipose tissue index (VATI), and mesorectal adipose tissue index (MATI) than non-responders. IVCS-responding CD individuals had lower VATI and mesenteric fat index (MFI) than non-responders. CD patients with a prolonged disease duration had a decreased SATI and an elevated MFI. VATI and MATI were reduced as UC clinically progressed, while more prominent clinical activity in CD correlated with increased VATI, MATI, and MFI. A high SATI indicated that patients with UC were more prone to be IVCS responders. For patients with CD, levels of VATI and MFI were negatively associated with effective IVCS treatment. The established models showed a discriminative accuracy of 0.834 [95% confidence interval (CI) 0.740–0.928] in the UC cohort and 0.871 (95% CI 0.793–0.949) in the CD cohort. Repeated samples supported the reliability of the developed models (AUCUC = 0.836, 95% CI 0.735–0.919; AUCCD = 0.876, 95% CI 0.785–0.946).ConclusionHuman fat indexes represent novel imaging biomarkers for identifying IBD patients who respond to IVCS, thus building accelerated therapy regimens and avoiding the adverse effects of ineffective IVCS.

Effects of Probiotics on Colitis-Induced Exacerbation of Alzheimer's Disease in AppNL-G-F Mice.

Alzheimer's disease (AD) is characterized by progressive cognitive decline and is a leading cause of death in the United States. Neuroinflammation has been implicated in the progression of AD, and several recent studies suggest that peripheral immune dysfunction may influence the disease. Continuing evidence indicates that intestinal dysbiosis is an attribute of AD, and inflammatory bowel disease (IBD) has been shown to aggravate cognitive impairment. Previously, we separately demonstrated that an IBD-like condition exacerbates AD-related changes in the brains of the AppNL-G-F mouse model of AD, while probiotic intervention has an attenuating effect. In this study, we investigated the combination of a dietary probiotic and an IBD-like condition for effects on the brains of mice. Male C57BL/6 wild type (WT) and AppNL-G-F mice were randomly divided into four groups: vehicle control, oral probiotic, dextran sulfate sodium (DSS), and DSS given with probiotics. As anticipated, probiotic treatment attenuated the DSS-induced colitis disease activity index in WT and AppNL-G-F mice. Although probiotic feeding significantly attenuated the DSS-mediated increase in WT colonic lipocalin levels, it was less protective in the AppNL-G-F DSS-treated group. In parallel with the intestinal changes, combined probiotic and DSS treatment increased microglial, neutrophil elastase, and 5hmC immunoreactivity while decreasing c-Fos staining compared to DSS treatment alone in the brains of WT mice. Although less abundant, probiotic combined with DSS treatment demonstrated a few similar changes in AppNL-G-F brains with increased microglial and decreased c-Fos immunoreactivity in addition to a slight increase in Aβ plaque staining. Both probiotic and DSS treatment also altered the levels of several cytokines in WT and AppNL-G-F brains, with a unique increase in the levels of TNFα and IL-2 being observed in only AppNL-G-F mice following combined DSS and probiotic treatment. Our data indicate that, while dietary probiotic intervention provides protection against the colitis-like condition, it also influences numerous glial, cytokine, and neuronal changes in the brain that may regulate brain function and the progression of AD.

The effect of vitamin D on haemoglobin, patient assessed disease activity and endoscopic assessment in ulcerative colitis patients with anaemia

Background: Anemia has a dramatic impact on patient's quality of life, yet anemia in patients with UC is still underdiagnosed and undertreated. Hepcidin has been identified to be a central regulator of iron absorption from the intestines and of plasma iron levels. In this study we evaluated the effect of vitamin D supplementation on haemoglobin levels, patient assessed disease activity and endoscopic assessment in ulcerative colitis (UC). Methods: In this prospective, open-labeled, parallel-group, randomized, comparative clinical study, we assigned newly diagnosed cases of UC with haemoglobin levels between 8-11 gm/dL to receive either standard therapy for 12 weeks or to receive oral 4000IU vitamin D3 along with standard therapy for 12 weeks. Results: Data from 60 patients were analyzed after 12 weeks. Supplementation with vitamin D3 significantly raised haemoglobin level in treatment group from (9.09±0.20) (Mean ± SEM) at baseline to 9.62±0.22 (Mean ± SEM) at 12 weeks. On assessment of abdominal pain with NRS scale at the end of treatment at 12 weeks the reduction in NRS score was to 3.47±0.29 in group I and to 2.23±0.21 in group II (p=0.0012) which was highly significant. There was also a statistically significant reduction in the Likert scale at the end of 4, 8 and 12 weeks in both groups. At week 12, there was no statistical difference between the two groups in improving the endoscopy score. Conclusions: Daily high dose vitamin D supplementation is beneficial in ameliorating UC symptoms like abdominal pain and has a positive effect on haemoglobin levels.

Fecal lactoferrin early predicts long-term outcomes in ulcerative colitis: A post-hoc analysis of the UNIFI and PURSUIT trials.

Fecal lactoferrin (FL) is associated with disease activity and relapse in ulcerative colitis. However, whether FL could early predict long-term outcomes in ulcerative colitis is poorly understood. This post-hoc analysis included participants who received biologics and had available data of FL concentration at week 4 from the UNIFI and PURSUIT trials (n=1063). Therapeutic outcomes, including clinical remission, endoscopic improvement and remission, and histological improvement and remission, were evaluated at the end of maintenance therapy. The incidence of colectomy was observed from week 0 to maximum week 228 in the PURSUIT trial (n=667). Multivariate logistic and Cox proportional-hazard regression were conducted to evaluate the associations between FL and therapeutic outcomes and colectomy, respectively. A high FL level at week 4 was associated with poor long-term clinical, endoscopic and histologic outcomes. FL >84.5μg/mL predicted a low likelihood of clinical (OR [95% CI]: 0.43 [0.32, 0.57]; p<0.001), endoscopic (OR [95% CI]: 0.40 [0.29, 0.56]; p<0.001), and histological (OR [95% CI]: 0.27 [0.14, 0.53]; p<0.001) remission. Moreover, week-4 FL could add prognostic value to fecal calprotectin and clinical and endoscopic scores for informing long-term therapeutic outcomes. For the risk of colectomy, patients with week-4 FL <20.1 and ≥20.1µg/mL had an incidence rate of 1.10% and 6.39%, respectively. Patients with FL ≥20.1µg/mL had a 995% higher risk of colectomy (HR [95% CI], 10.95 [1.45, 82.74]). FL could be a promising prognostic biomarker for long-term therapeutic outcomes and risk of colectomy in patient of ulcerative colitis.