Including Inflammatory Bowel Disease Patients Research Articles

Abstract 5636: CUX1 transcriptionally regulates intestinal epithelial homeostasis

Abstract The small intestine digests and absorbs nutrients, a role made possible by specialized secretory and absorptive cells that constantly replenish from the intestinal stem cell niche. Disruption in intestinal epithelium homeostasis has been linked to pathologies including inflammatory bowel disease (IBD) and cancer. However, the processes regulating differentiation in healthy and disease setting are incompletely understood. CUX1 is a highly conserved homeodomain-containing transcription factor that is expressed in small intestinal crypts and has been previously shown to be essential in mice and Drosophila. CUX1 is upregulated upon inflammatory stress conditions, including intestinal damage and in IBD. In addition, CUX1 is predicted to be protective against IBD from genome-wide association studies. The aim of the current work is to determine the mechanistic role of CUX1 in secretory intestinal cells differentiation and epithelial homeostasis. To this end, we have generated transgenic mouse models that modulate CUX1 levels in an inducible manner. Mice with near-null CUX1 levels exhibit rapid weight loss requiring euthanasia while mice with ~50% residual CUX1 halt normal weight gain. Histologic examination of tissues from mice with CUX1 knock-down reveals a lack of mature secretory cells, including goblet and Paneth cells, the latter playing a supportive role to intestinal stem cells. Moreover, mouse intestinal tissues from our knock-down models demonstrated decreased proliferation with increased apoptosis. In transcriptome profiling, we observed downregulation of proliferation, intestinal stem cell, and digestive system developmental gene signatures and decreased levels of key secretory cell regulators, pointing towards a role for CUX1 in stem cell maintenance and differentiation. Indeed, reducing CUX1 levels decreased β-catenin protein levels, while Wnt/β-catenin signaling is required for the organization of the crypt-villus axis. Finally, CUX1 knock-down compromises the ability to form budding organoids, demonstrating the cell intrinsic role for CUX1 in stem cell differentiation. In ongoing studies, we are identifying CUX1 genome-wide binding targets and the epigenetic impact of CUX1 in intestinal epithelium cells. Our findings indicate that CUX1 is a critical regulator of intestinal epithelium homeostasis that has a role in differentiation and potential role in injury-induced de-differentiation in healthy as well as IBD patients. We propose that CUX1 regulates stem cell maintenance and crypt composition by regulating Wnt/β-catenin signaling and inducing fetal-like transcriptomic repair program shown to be coopted by colon cancers. Resolving an intricate network of transcriptional regulation of differentiation in the intestinal crypt holds the potential to successfully target inflammation-related damage in human intestines. Citation Format: Katarzyna Zawieracz, Ningfei An, Megan McNerney. CUX1 transcriptionally regulates intestinal epithelial homeostasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5636.

A5 DEVELOPMENT OF A PRE-CLINICAL MOUSE MODEL TO INVESTIGATE ADVERSE FOOD REACTIONS IN INTESTINAL INFLAMMATION

Abstract Background Patients with chronic intestinal conditions, including inflammatory bowel disease (IBD), experience diverse food-related adverse reactions. However,, the precise mechanisms of food intolerances in IBD remains unclear. Emerging evidence suggests that altered diet-microbiota interactions can contribute to the development of IBD. Previously we shown that intestinal microbiota plays an important role in the development of food intolerances. We hypothesize that microbial alterations in IBD patients facilitate adverse reactions to foods. Aims To establish a preclinical mouse model to study adverse food reactions in intestinal inflammation. Methods Eight-week-old C57BL/6 mice were treated with 3% dextran sodium sulfate (DSS) for 5 days, then divided into three groups. The first group was sensitized to dairy protein (3% casein and 3% whey), using 4 oral administrations of cholera toxin over 2 weeks, without any further diet intervention. The second group was also sensitized to casein and whey, then after 1 week of recovery, the mice were subsequently place on a chow containing casein and whey. Finally, the third group was subjected to diet intervention without sensitization. The same experiment was repeated in a different subset of C57BL/6 mice which included a second cycle of DSS (1.5%) during the dietary interventions. Markers of intestinal inflammation (disease activity index (DAI), histological damage, cell infiltration and pro-inflammatory genes expression (NanoString)) and intestinal microbiota were analysed after 1 week of the diet intervention. Results Mice previously sensitized on the dairy diet exhibited an enhanced activation of immune cells after intestinal inflammation. While the histological damage score did not reveal significant differences among experimental groups, the sensitized group under dairy intervention exhibited an elevated level of immune cell infiltration, increasing the polymorphonuclear, CD3+ and mast cells. Gene expression also revealed that dairy induced the expression of inflammatory genes, such as C6, Arg1, Tnf, Il6, Cxcl9 and Cxcl10. When animals are subjected to a second DSS-cycle, dairy worsen colitis in mice previously sensitized, as shown by higher DAI compared to group with control diet and dairy diet without sensitization. Conclusions In the context of intestinal inflammation, dairy protein leads to immune activation characterized by an increase in polymorphonuclear cells, mast cells and lymphocytes, as well as worsening colitis. Future studies using this model will provide valuable insights into the role of intestinal microbiota in food intolerances associated with intestinal inflammation. Funding Agencies CCC

The Role of Methanogenic Archaea in Inflammatory Bowel Disease-A Review.

Methanogenic archaea are a part of the commensal gut microbiota responsible for hydrogen sink and the efficient production of short-chain fatty acids. Dysbiosis of methanogens is suspected to play a role in pathogenesis of variety of diseases, including inflammatory bowel disease (IBD). Unlike bacteria, the diversity of archaea seems to be higher in IBD patients compared to healthy subjects, whereas the prevalence and abundance of gut methanogens declines in IBD, especially in ulcerative colitis. To date, studies focusing on methanogens in pediatric IBD are very limited; nevertheless, the preliminary results provide some evidence that methanogens may be influenced by the chronic inflammatory process in IBD. In this review, we demonstrated the development and diversity of the methanogenic community in IBD, both in adults and children.

P1140 Complementary and alterantive medicicne in patients with Inflammatory Bowel Disease in Poland

Abstract Background There is an increasing interest in complementary and alternative medicine (CAM) in patients with chronic diseases, including inflammatory bowel disease (IBD). We decided to investigate this problem because there is still not much data on this interesting and underestimated topic. Methods This single-center, cross-sectional study was conducted between October 2021 and June 2022 among patients of the Department of Gastroenterology of the National Institute of Medicine of the Ministry of Internal Affairs and Administration, both hospitalized and outpatients. Patients with IBD were asked to complete an anonymous survey that included questions about the use of CAM, their type and reason for use. The questionnaire also included data on the course of the disease, treatment and socio-demographic information. The results of qualitative variables were expressed as frequencies and percentages. We used the chi-square and Mann-Whitney U tests. Results 435 patients were included in the study: 203 women (46.9%) and 230 men (53.1%). In this group, there were 250 (58.5%) with Crohn's disease (CD) and 177 (41.5%) with ulcerative colitis (UC). The average duration of the disease is 10.9 years. A little more than a half of patients received immunosuppressive and biological treatment. Among respondents, 66.9% (291) had ever used CAM. CAM was statistically more frequently used by people treated with immunosuppressive 60.26% (p=0.002) and biological drugs 72.51% (p=0.004), as well as people with higher education 71.75% (p=0.006) and secondary education 58.97 % (p=0.009), living in large cities 73.63% (p=0.006) and earning the highest income 85.51% (p<0.001). Age, gender, disease duration, use of other drugs (5-ASA, steroids) and disease diagnosis (UC vs. CD) did not influence the use of CAM. As many as 74.1% of CAM users use various types of dietary supplements. 61.5% of respondents follow special diets, 56.9% take probiotics, and 53.4% take herbs. Patients most often gain knowledge about CAM from other patients, family members (76.3%) and from the Internet (76.3%). The treatment is carried out independently, without medical supervision, and only 62.1% of patients inform the gastroenterologist about the use of CAM. Conclusion Our research shows that CAM is very often used by IBD patients in Poland, especially among patients with severe disease treated with immunosuppressive and biological therapy. This is particularly important for patient safety, taking into account the possible risk of interactions with conventional drugs and the usually lack of medical supervision.

P323 Defining Normal Bowel Wall Thickness on Intestinal Ultrasound in an International Multicenter Cohort of Children with Inflammatory Bowel Disease in Sustained Deep Remission

Abstract Background Intestinal ultrasound (IUS) is a non-invasive, patient-centric tool for detecting and monitoring activity in patients with inflammatory bowel disease (IBD). Bowel wall thickness (BWT) is the most important parameter for assessing IBD activity, however, normal values are extrapolated from adults. We aimed to define normal BWT in children with IBD who achieved sustained deep remission. Methods International, multicentre, retrospective, pediatric IUS database including IBD patients (< 18 years) without a prior history of surgery or complications who underwent IUS after achieving sustained deep remission: absence of ulcerations on ileocolonoscopy and/or transmural healing on magnetic resonance enterography or computed tomography enterography and steroid-free clinical remission from 2020-2023. Descriptive statistics summarized data as percentages for categorical variables and median [IQR] for continuous variables. Primary outcome was median BWT by segment: sigmoid colon (SC), descending colon (DC), transverse colon (TC), ascending colon (AC), and terminal ileum (TI), assessed using Kruskall Wallis. Secondary outcomes included univariate association of BWT and age, sex, disease duration, diagnosis (Crohn’s disease (CD) vs. ulcerative colitis (UC)/IBD-unspecified (IBD-U) and medication exposure. Results 80 patients (33 (41%) female; 51 (64%) CD:26 (33%)UC:3 (4%)IBD-U, median age 15.2 [14-16.6] years) with 400 bowel segments were included. Forty (50%) received anti-tumor necrosis factor therapy (anti-TNF), 18 (23%) ustekinumab (UST), 10 (12%) mesalamine(5-ASA), 6 (8%) vedolizumab (VDZ), 5 (6%) immunomodulator monotherapy (IM), and 1 (1%) upadacitinib (UPA) (Table 1). Median BWT was 1.3 [1.0-1.6]mm for SC, 1.3 [1.1-1.7]mm for DC, 1.3 [1.0-1.6] mm for TC, 1.3 [1.0-1.6]mm for AC, and 1.3 [1.1-1.5]mm for TI (Figure 1). There was no difference in BWT between segments (p=0.7952), age (p=0.1952) or sex (p=0.781). BWT was negatively associated with disease duration (p<0.05). UC patients had a 0.16 mm thinner BWT than CD (p<0.05). Mean BWT in patients on VDZ was thinner than those on anti-TNF monotherapy (-0.19mm, p<0.05). BWT in patients on anti-TNF combination therapy was thicker than patients on anti-TNF monotherapy (0.21mm, p<0.05). There was no BWT difference between patients on IM, 5-ASA and UST compared to anti-TNF (p>0.05). Conclusion Normal BWT for children with IBD in deep remission is less than adults, and unaffected by age, sex and bowel segment. BWT may be affected by disease duration, phenotype and medication exposure. These findings are crucial to the standardized assessment of transmural healing in children with IBD.

P474 IBD-Disk : Towards validating the classical Arabic version of the questionnaire ?

Abstract Background The IBD-Disk is a validated 10-question, self-administered visual questionnaire used to assess the inflammatory bowel disease (IBD) related disability. It has been translated into several languages and validated in different populations since its emergence. The aim of our study is to explore the internal consistency and item reliability of the IBD-Disk in its classical Arabic version, and to analyze the strength of correlation between each item and the sum of the scale. Methods We conducted a monocentric cross-sectional study including IBD patients. All individuals completed the IBD-Disk questionnaire in classical Arabic. The internal consistency of the IBD-Disk was assessed using Cronbach's alpha between item combinations. A value > 0.70 was considered acceptable, > 0.80 good, and > 0.90 excellent. Cronbach's corrected correlation was assessed using Pearson's correlation coefficient. Results We included 166 patients, 53.6% were men and 69.3% had Crohn's disease. Median age was 38 years [30 - 48]. The mean total score was 36.4 ± 21.0. The "Energy", "Emotions" and "Education & work" items had the highest scores (4.9 ± 2.9, 4.7 ± 3.1, and 4.4 ± 3.2 respectively). Including the 10 items of the IBD-Disk scale, a value of 0.913 95% CI [0.893-0.932] was observed for Cronbach's alpha, demonstrating good reliability between the different sub-scores. By performing the removal procedure one by one, Cronbach's alpha varied between 0.902 and 0.915, confirming that all items contribute to the construct. In addition, all items showed a Cronbach corrected correlation between each item and the rest of the scale r > 0.4, p<0.001. Energy showed the highest correlation (r=0.751), and joint pain the lowest (r=0.506) (Table 1). Also, Cronbach's alpha was positive for every pair of IBD-Disk items at the start of the study. The item pairs that showed the best correlation were [Abdominal pain - Regulating defecation], [Energy - Regulating defecation] and [Energy - Sleep]. In contrast, the item pairs that were least interconnected were [Abdominal pain - Joint pain], [Interpersonal interaction - Joint pain] and [Body image - Joint pain] (Table 2). Conclusion Our work has demonstrated excellent item homogeneity in the classical Arabic version of the IBD-Disk, and a good correlation between each item and the remaining total score. However, a prospective measurement of the intra-class correlation coefficient of the classical Arabic version will be necessary to assess its reproducibility over time.

Facteurs de risque de lésions malpighiennes intra-épithéliale de haut grade ou de cancer du col de l’utérus en cas de maladie inflammatoire chronique de l’intestin

IntroductionChronic inflammatory bowel disease (IBD) is thought to increase the risk of high-grade histological intraepithelial lesions (HGIL) and cervical cancer. The risk factors for developing these lesions are poorly understood. Materials and methodsThis is a single-center retrospective case-control study including IBD patients followed at our University Hospital Center from 2011 to 2021 who presented with HGIL or cervical cancer. Four controls were case-matched according to IBD type, age, active smoking and multiparity. ResultsEighteen cases and 72 controls were included. We found no significant differences between the 2 groups with regard to mean age at IBD diagnosis, mean duration of IBD, IBD location, history of IBD-related surgery or even association with another chronic inflammatory disease. In our study, the use of immunosuppressants/biotherapies in these patients [50% (9/18) for cases vs. 56% (40/72) for controls; P=0.9] was not a risk factor for IGRA or cervical cancer. Similarly, neither the total duration of exposure to immunosuppressants/biotherapies (9.9±8years for cases vs. 6.6±5.3years for controls; P=0.1), nor combined therapies [11% (2/18) for cases vs. 6% (4/72) for controls; P=0.3], nor azathioprine or methotrexate use [22% (4/18) for cases vs. 11% (8/72) for controls; P=0.3] were found to be risk factors. ConclusionIn our study, we found no risk factors for patients with IBD to develop IGRA or cervical cancer.

Population pharmacokinetics and pharmacodynamics of efmarodocokin alfa (IL-22Fc).

Efmarodocokin alfa (IL-22Fc) is a fusion protein of human IL-22 linked to the crystallizable fragment (Fc) of human IgG4. It has been tested in multiple indications including inflammatory bowel disease (IBD). The purposes of the present analyses were to describe the population pharmacokinetics (PK) of efmarodocokin alfa and perform pharmacodynamic (PD) analysis on the longitudinal changes of the PD biomarker REG3A after efmarodocokin alfa treatment as well as identify covariates that affect efmarodocokin alfa PK and REG3A PD. The data used for this analysis included 182 subjects treated with efmarodocokin alfa in two clinical studies. The population PK and PD analyses were conducted sequentially. Efmarodocokin alfa concentration-time data were analyzed using a nonlinear mixed-effects modeling approach, and an indirect response model was adopted to describe the REG3A PD data with efmarodocokin alfa serum concentration linked to the increase in REG3A. The analysis software used were NONMEM and R. A 3-compartment model with linear elimination best described the PK of efmarodocokin alfa. The estimated population-typical value for clearance (CL) was 1.12L/day, and volume of central compartment was 6.15L. Efmarodocokin alfa CL increased with higher baseline body weight, C-reactive protein, and CL was 27.6% higher in IBD patients compared to healthy subjects. The indirect response PD model adequately described the longitudinal changes of REG3A after efmarodocokin alfa treatment. A popPK and PD model for efmarodocokin alfa and REG3A was developed and covariates affecting the PK and PD were identified.

The Role of Serum Calgranulin C as a Non-Invasive Marker for Inflammatory Bowel Disease

Abstract Background IBD has been recognized as a systemic inflammatory entity and as such, it is anticipated to induce changes exceeding the boundaries of bowel mucosa, being reflected in a broader spectrum of tissues, including blood. Calgranulin c is a calcium binding protein with proinflammatory properties. It has been associated with different diseases of inflammatory origin, including inflammatory bowel disease (IBD). In our present study, the utility of serum calgranulin c as marker for inflammatory bowel disease was tested. Objective is to evaluate the role of serum calgranulin c as a diagnostic and prognostic marker in IBD patients and to correlate it's level with different biochemical, endoscopic and clinical parameters. Patients and Methods Calgranulin c serum levels were determined in 50 patients with ulcerative colitis (UC), 20 patients with Crohn’s disease (CD) and 73 with functional bowel disorder (IBS). Calgranulin c serum concentrations were analysed using double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) to assay the level of Human S100 Calcium Binding Protein A12(S100A12) in samples. Results In the present study we found that the mean serum calgranulin c were 723.640±529.055 ng/ml (range: 63-2000) in UC, 759.233±797.963 ng/ml (range: 110-2000) in CD and 80.850±24.416 ng/mL (range: 52-135) in control group. UC and CD patients had significantly higher serum calgranulin c levels compared to IBS patients with p < 0.001 for both. the best cut-off for serum calgranulin c levels in prediction of IBD was >110 ng/Ml with sensitivity 96.67%, specificity 85.00%, and test accuracy was 97.8%. best cut-off for serum calgranulin c levels in prediction of UC was >135 ng/mL. the best cut-off for serum calgranulin c levels in prediction of CD was >110 ng/Ml. Moreover, the best cut-off for serum calgranulin c levels of > 435 ng/mL could predict activity in UC group depend on UCEIS, depend on ACGUCAI and Erosions and ulcers in endoscopy. another cut off level of Serum calgranulin c in prediction of luminal bleeding in endoscopy in UC patients was >625 ng/ml. the best cut off level of Serum calgranulin c in prediction of activity among CD patients depend on CDAI was >437 ng/ml. Conclusion Serum calgranulin c was found to be higher in patients with IBD than with functional bowel disorded (IBS). Levels of serum calgranulin c varied significantly with disease severity in patients with UC and CD. Serum calgranulin c was found to be higher among patients with active CD and UC than those in remission. Serum calgranulin c can be used as a non invasive marker of inflammatory bowel disease. It can distinguish IBD from IBS and can be considered as a maker of activity in IBD patients.

HLA-DQA1*05 Was Not Associated With Primary Nonresponse or Loss of Response to First Anti-TNF in Real-World Inflammatory Bowel Disease Patients.

We lack predictors of response to biologics in the management of patients with inflammatory bowel disease (IBD). A recent study has shown a significant association between HLA-DQA1*05 carriers and the development of loss of response to anti-tumor necrosis factor (TNF) mediated by immunogenicity. Retrospective single-center cohort study including IBD patients who had received anti-TNF therapy as a first biologic and whose HLA-DQA1*05 had been determined. Primary nonresponse and secondary failure (assessed by survival analysis) have been evaluated as well as safety outcomes. A total of 199 IBD patients (161 [81%] with Crohn's disease and 38 [19%] with ulcerative colitis) were included. A total of 42.4% were HLA-DQA1*05 carriers and 60% received combination therapy at the start of anti-TNF treatment. Median follow-up was 24 (interquartile range, 11-66) months. No statistically significant differences were found in primary nonresponse to anti-TNF (89.3% vs 87.8%; P = .825), depending on HLA carriers and noncarriers. No differences in secondary loss of response according to HLA variant in any of the analyses performed (full cohort, according to IBD or anti-TNF type) were observed. Again, no differences were observed in patients treated with combination therapy. In terms of safety, no significant differences were found in the rate of infusion reactions or serious adverse events. In our real-life cohort of IBD patients treated for the first time with anti-TNF, being an HLA-DQA1*05 carrier did not act as a predictor of response failure, either primary or secondary. The safety of anti-TNF treatment has also not been influenced by the variant.

Application of untargeted volatile profiling in inflammatory bowel disease research

Inflammatory bowel disease (IBD) diagnosis depends on criteria based on histological, endoscopic, radiological, and clinical results. These studies show drawbacks as being expensive, invasive, and time-consuming. In this work, an untargeted metabolomic strategy based on the monitoring of volatile compounds in serum by headspace gas chromatography–mass spectrometry is proposed as a complementary, fast, and efficient test for IBD patient diagnosis. To develop the method and build a chemometric model that allows the IBD diagnosis, serum samples including IBD patients and healthy volunteers were collected. Analyses were performed by incubating 400 µL of serum for 10 min at 90 °C. For data processing, an untargeted metabolomic strategy was used. A total of 96 features were detected, of which a total of 10 volatile compounds could be identified and confirmed by means of the analysis of real standards. The chemometric treatment consisted of a discriminant analysis of orthogonal partial least squares (OPLS-DA) obtaining a 100% of classification rate, since all the analyzed samples were correctly classified.Graphical abstract

A Clinical and Pathophysiological Overview of Intestinal and Systemic Diseases Associated with Pancreatic Disorders: Causality or Casualty?

The relationship between chronic intestinal disease, including inflammatory bowel disease (IBD) and celiac disease (CelD), and pancreatic disorders has been little investigated. Although an increased risk of acute pancreatitis (AP), exocrine pancreatic insufficiency with or without chronic pancreatitis, and chronic asymptomatic pancreatic hyperenzymemia have been described in these patients, the pathogenetic link remains unclear. It may potentially involve drugs, altered microcirculation, gut permeability/motility with disruption of enteric-mediated hormone secretion, bacterial translocation, and activation of the gut-associated lymphoid tissue related to chronic inflammation. In addition, the risk of pancreatic cancer seems to be increased in both IBD and CelD patients with unknown pathogenesis. Finally, other systemic conditions (e.g., IgG4-related disease, sarcoidosis, vasculitides) might affect pancreatic gland and the intestinal tract with various clinical manifestations. This review includes the current understandings of this enigmatic association, reporting a clinical and pathophysiological overview about this topic.

Natural Coumarin Derivatives Activating Nrf2 Signaling Pathway as Lead Compounds for the Design and Synthesis of Intestinal Anti-Inflammatory Drugs.

Nrf2 (nuclear factor erythroid 2-related factor 2) is a transcription factor related to stress response and cellular homeostasis that plays a key role in maintaining the redox system. The imbalance of the redox system is a triggering factor for the initiation and progression of non-communicable diseases (NCDs), including Inflammatory Bowel Disease (IBD). Nrf2 and its inhibitor Kelch-like ECH-associated protein 1 (Keap1) are the main regulators of oxidative stress and their activation has been recognized as a promising strategy for the treatment or prevention of several acute and chronic diseases. Moreover, activation of Nrf2/keap signaling pathway promotes inhibition of NF-κB, a transcriptional factor related to pro-inflammatory cytokines expression, synchronically promoting an anti-inflammatory response. Several natural coumarins have been reported as potent antioxidant and intestinal anti-inflammatory compounds, acting by different mechanisms, mainly as a modulator of Nrf2/keap signaling pathway. Based on in vivo and in vitro studies, this review focuses on the natural coumarins obtained from both plant products and fermentative processes of food plants by gut microbiota, which activate Nrf2/keap signaling pathway and produce intestinal anti-inflammatory activity. Although gut metabolites urolithin A and urolithin B as well as other plant-derived coumarins display intestinal anti-inflammatory activity modulating Nrf2 signaling pathway, in vitro and in vivo studies are necessary for better pharmacological characterization and evaluation of their potential as lead compounds. Esculetin, 4-methylesculetin, daphnetin, osthole, and imperatorin are the most promising coumarin derivatives as lead compounds for the design and synthesis of Nrf2 activators with intestinal anti-inflammatory activity. However, further structure-activity relationships studies with coumarin derivatives in experimental models of intestinal inflammation and subsequent clinical trials in health and disease volunteers are essential to determine the efficacy and safety in IBD patients.

Effectiveness of Vitamin D Supplementation on Disease Course in Inflammatory Bowel Disease Patients: Systematic Review With Meta-Analysis.

The vitamin D role in bone metabolism is well known; however, recent evidence suggests the impact of vitamin D in immune modulation and its implications in immune-mediated diseases, including inflammatory bowel disease (IBD). We performed a systematic review with meta-analysis by a specific protocol (PROSPERO: CRD42022311184; March 2022, https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=311184). Randomized clinical trials involving IBD patients treated with vitamin D supplementation, compared with placebo, that evaluated the risk of clinical relapse and disease activity were included. Literature search was performed using Medline, Scopus, and Cochrane CENTRAL through January 2022. Out of 1448 articles, 12 (11 full-texts and 1 abstract) were included. Seven randomized clinical trials reported data on the clinical relapse as dichotomous outcome, while 7 studies reported data on disease activity expressed as continuous variables. The pooled risk ratio of clinical relapse was 0.64 (95% confidence interval, 0.46-0.89; I2 = 25%) among 458 IBD patients. However, this seems to be solid only in Crohn's disease (CD) patients. In fact, only 2 studies, involving 67 patients with ulcerative colitis, were included in the analysis. CD patients in clinical remission had a strong significant risk reduction in clinical relapse (risk ratio, 0.47; 95% confidence interval, 0.27-0.82; I2 = 0%), suggesting that it could be a specific subgroup with maximum clinical benefit of vitamin D supplementation. This meta-analysis shows that vitamin D supplementation can reduce the risk of clinical relapse in IBD patients, especially in CD patients in clinical remission. In a subgroup analysis, it was not significant (due to small number of studies and low number of patients), and well-powered studies are needed, in particular for ulcerative colitis patients.

Dynamic Population of Gut Microbiota as an Indicator of Inflammatory Bowel Disease

Inflammatory bowel disease is a chronic inflammatory disease of the gastrointestinal tract. The gut microbiota is an important factor in the pathogenesis of inflammatory bowel disease (IBD). Due to a link between the gut microbiota and IBD, studying microbiota changes using an accurate, sensitive and rapid method for detection of the disease seems necessary. This study aimed to compare the composition of gut microbiota in three groups of people, including IBD patients, cured Inflammatory bowel disease (CIBD), and healthy groups. For this study, 45 stool samples (15 from each group) were collected. Using real-time PCR, the abundance of 11 bacterial 16S rRNA gene sequences was examined. In the IBD group, the number of three bacterial phyla, including Firmicutes, Actinobacteria, and Bacteroidetes, decreased (p < 0.01, p < 0.01, and p < 0.001, respectively), while the population of γ-Proteobacteria increased significantly (p < 0.0001). In the CIBD group, the number of Actinobacteria enhanced (p < 0.01), but that of Bacteroidetes and Firmicutes decreased (p < 0.01, and p < 0.05, respectively). Findings of this study indicate that decrease in Firmicutes and increase in γ-Proteobacteria could be used as an indicator of IBD instead of employing invasive and costly detection methods such as colonoscopy and other tests.

Misconceptions Drive COVID-19 Vaccine Hesistancy in Individuals with Inflammatory Bowel Disease.

Background Vaccination is an effective public health measure to combat the SARS-CoV-2 pandemic. However, vaccine “hesitancy” has limited uptake in some, including inflammatory bowel disease (IBD) patients who may have unique concerns influencing uptake. Aim The aim of the study is to explore attitudes, concerns, and the influence of different sources of information on COVID-19 vaccine uptake in IBD patients. Methods Patients from a specialist IBD clinic at a tertiary hospital in Australia and a national IBD patient society were invited to complete an anonymous online survey regarding COVID-19 vaccination. Demographic characteristics, attitudes towards vaccination, and trust in sources of information were explored. Logistic regression was used to identify variables associated with vaccine uptake. Results Of 441 respondents, 93% of respondents had received at least 1 dose of COVID-19 vaccination. Self-perceived risk of being more unwell with COVID-19 infection due to IBD (AOR 5.25, 95% CI 1.96–14.04, p < 0.001) was positively associated with vaccine uptake. Concerns regarding the safety of vaccination in pregnancy (OR 0.22, 95% CI 0.08–0.65, p=0.006) and of causing an IBD flare (OR 0.28, 95% CI 0.10–0.77, p=0.01) were negatively associated with vaccine uptake. In total, 282 (73.7%) responders ranked healthcare workers the most trusted source to obtain information surrounding vaccination. Conclusion Vaccine hesitancy in IBD patients is low. Concerns about the safety of vaccination in pregnancy and in causing an IBD flare are both associated with vaccine hesitancy. Healthcare providers play a key role in proactively addressing these misconceptions particularly in the context of emerging virus variants and the availability of boosters.

Under the Umbrella of Clinical Pharmacology: Inflammatory Bowel Disease, Infliximab and Adalimumab, and a Bridge to an Era of Biosimilars.

Monoclonal antibodies (MAbs) have revolutionized the treatment of many chronic inflammatory diseases, including inflammatory bowel disease (IBD). IBD is a term that comprises two quite similar, yet distinctive, disorders—Crohn’s disease (CD) and ulcerative colitis (UC). Two blockbuster MAbs, infliximab (IFX) and adalimumab (ADL), transformed the pharmacological approach of treating CD and UC. However, due to the complex interplay of pharmacology and immunology, MAbs face challenges related to their immunogenicity, effectiveness, and safety. To ease the burden of IBD and other severe diseases, biosimilars have emerged as a cost-effective alternative to an originator product. According to the current knowledge, biosimilars of IFX and ADL in IBD patients are shown to be as safe and effective as their originators. The future of biosimilars, in general, is promising due to the potential of making the health care system more sustainable. However, their use is accompanied by misconceptions regarding their effectiveness and safety, as well as by controversy regarding their interchangeability. Hence, until a scientific consensus is achieved, scientific data on the long-term effectiveness and safety of biosimilars are needed.

Evolutionary Insights Into Microbiota Transplantation in Inflammatory Bowel Disease.

The intestinal microbiome plays an essential role in human health and disease status. So far, microbiota transplantation is considered a potential therapeutic approach for treating some chronic diseases, including inflammatory bowel disease (IBD). The diversity of gut microbiota is critical for maintaining resilience, and therefore, transplantation with numerous genetically diverse gut microbiota with metabolic flexibility and functional redundancy can effectively improve gut health than a single probiotic strain supplement. Studies have shown that natural fecal microbiota transplantation or washing microbiota transplantation can alleviate colitis and improve intestinal dysbiosis in IBD patients. However, unexpected adverse reactions caused by the complex and unclear composition of the flora limit its wider application. The evolving strain isolation technology and modifiable pre-existing strains are driving the development of microbiota transplantation. This review summarized the updating clinical and preclinical data of IBD treatments from fecal microbiota transplantation to washing microbiota transplantation, and then to artificial consortium transplantation. In addition, the factors considered for strain combination were reviewed. Furthermore, four types of artificial consortium transplant products were collected to analyze their combination and possible compatibility principles. The perspective on individualized microbiota transplantation was also discussed ultimately.

Metabolic Molecular Diagnosis of Inflammatory Bowel Disease by Synergistical Promotion of Layered Titania Nanosheets with Graphitized Carbon.

The online version contains supplementary material available at 10.1007/s43657-022-00055-0.

SARS-CoV-2-inactivated vaccine hesitancy and the safety in inflammatory bowel disease patients: a single-center study.

Background:The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine is thought to be the most effective preventive method of controlling the coronavirus disease 2019 (COVID-19) epidemic. Some patients with immune-related diseases, including inflammatory bowel disease (IBD) patients, however, may hesitate to be vaccinated for various reasons. Although several guidelines recommend vaccinating all IBD patients with inactivated SARS-CoV-2 vaccines, there is still a lack of real-world data on the safety of inactivated SARS-CoV-2 vaccines and COVID-19 vaccination rate in IBD patients. In this study, we investigated the reasons for hesitancy in COVID-19 vaccination, the COVID-19 vaccination rate, and the safety of SARS-CoV-2-inactivated vaccination in patients with IBD.Methods:This was a retrospective study. A total of 418 participants with IBD were enrolled to calculate the vaccination rates. A total of 232 patients with IBD who did not receive SARS-CoV-2 vaccination were recruited to investigate the reasons for hesitation. A follow-up survey of 151 IBD patients and 188 healthy participants who had received the SARS-CoV-2-inactivated vaccination was conducted to analyze adverse reactions.Results:The COVID-19 vaccination rate was 49.3% and almost half of the participants were ‘Concerned about the safety of the vaccine (such as adverse reactions) due to IBD’. After SARS-CoV-2 vaccination, adverse reactions were mild or moderate. The adverse reactions in the IBD and non-IBD populations were roughly the same, and IBD medications did not increase the risk of adverse reactions.Conclusion:SARS-CoV-2-inactivated vaccination rates in IBD patients are still low and a significant proportion of patients are hesitant about the vaccine because of safety concerns. SARS-CoV-2-inactivated vaccination in patients with IBD appears to be safe.