Inflammatory Bowel Disease Subjects Research Articles

Inflammatory Bowel Diseases in the Elderly: A Focus on Disease Characteristics and Biological Therapy Patterns.

Background: The incidence of inflammatory bowel diseases (IBDs) in elderly patients is constantly increasing. It results from the combination of an aging population with compounding prevalence of IBD, as well as the growing burden of elderly-onset IBD. The clinical characteristics of elderly patients differ from young subjects with IBD due to the multimorbidity or polypharmacy, affecting the choice of adequate therapeutic options. The aim of this study was to determine the clinical aspects and biological therapy safety in elderly Polish IBD patients. Methods: We conducted a retrospective study aimed at describing the demographic, clinical, and management characteristics of IBD patients treated with a biological therapy in two referral centers within the National Drug Program in Poland. Results: Out of the entire group of 366 studied patients, 51 (13.9%) were aged over 60-32 with ulcerative colitis (UC) and 19 with Crohn's disease (CD). The disease location was predominantly ileocolonic (57.89%) in patients with CD and pancolitis for patients with UC (56.25%). Most of the elderly IBD subjects were characterized by significant comorbidities, with Charlson Comorbidity Index (CCI) ≥ 1 in 66.67% patients. The probability of stopping biological therapy due to adverse events had the tendency to be higher in the CCI ≥ 1 group (20.58% vs. 5.88% in CCI = 0; p = 0.087). The main reasons for the therapy discontinuation included hypersensitivity reactions and liver enzyme abnormalities. Conclusions: In conclusion, our results underline the importance of assessing the comorbidity status instead of the age prior to initiating biological therapy, analyzing additional safety risks, and close monitoring in IBD patients with multiple comorbidities.

Food-Related Quality of Life and Its Predictors in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is associated with dietary restrictions and food- and drink-driven daily life limitations. Food-related quality of life (FR-QoL) is still an under-addressed issue in IBD. We aimed to study determinants of FR-QoL in an IBD cohort, namely objective measures of disease activity. A cross-sectional case-control study was conducted in a Tertiary Hospital, including adult patients with IBD (cases) and blood donors or subjects referred for colorectal polypectomies (controls). Participants answered an anonymous multimodal questionnaire including sociodemographic and clinical data, the validated FR-QoL-29, and the SIBDQ tools. Patients' disease activity was previously assessed by a physician using symptom-based scores and biomarkers (Harvey-Bradshaw index, partial Mayo score, fecal calprotectin). A total of 239 patients with IBD and 126 controls were included. Patients with active disease had poorer FR-QoL than patients in remission (80.0 [56.0-99.0] vs. 103.5 [81.0-129.9], p < 0.001). Still, patients with IBD had significantly lower FR-QoL compared with controls (99.0 [76.0-126.0] vs. 126.0 [102.8-143.0], p < 0.001), irrespective of disease activity. FR-QoL correlated with health-related quality of life, measured by SIBDQ (r = 0.490, p < 0.001), and was significantly impaired by patients' depressive humor (84.0 [61.0-112.0] vs. 108.0 [88.0-130.5], p < 0.001). Globally, FR-QoL compromise was mostly related to persistent worries about food, concerns about food-related symptoms, and life disruption due to eating and drinking. Patients with IBD showed significant FR-QoL impairment, irrespective of disease type and activity. Related psychosocial factors, such as the patient's affective status and fear around eating, warrant a need for a multidisciplinary approach to IBD, including tailored nutritional counseling.

P1198 Pediatric inflammatory bowel diseases in patients with genetic syndromes: a case-control multicentre SIGENP study

Abstract Background Genetic syndromes are associated with a strong susceptibility to autoimmune disorders with an increased risk of developing inflammatory bowel diseases (IBD). However, data regarding the impact of genetics in the development of IBD are limited (Gatti S. et al, Frontiers in Pediatrics 2021). Furthermore, patients with genetic syndromes are affected by multiple comorbidities which increase diagnostic and therapeutic complexity as well as the risk of developing adverse reactions to drugs. Methods In this retrospective, multicenter case-control study, we recruited IBD children with a genetic syndrome (cases: group 1) and 2 matched IBD patients for each case (controls: group 2) comparable for gender, age at diagnosis, type of IBD and follow-up period. IBD subjects were diagnosed at 11 Italian pediatric IBD units between 2010 and 2022. Monogenic VEO-IBD were excluded. Genetic data were collected. Clinical and disease characteristics, presence of comorbidities, use of drugs and side effects, surgical outcomes and mortality were compared at diagnosis and at the last follow-up between the 2 groups. Results A total of 23 IBD children with a genetic condition/syndrome (Table 1) and 46 matched controls were identified. In all cases, except 5 the diagnosis of IBD followed the genetic diagnosis. Thirty patients had Crohn’s disease (CD) and 39 had Ulcerative Colitis (UC). The 2 groups were comparable in terms of gender, age at diagnosis (8,9±4.6 vs 9.4±4.4 years), duration of follow up (5.6±3.4 vs 4.1±2.9 years) and severity of disease at diagnosis evaluated by w-PCDAI (34,7±23,5 vs 43,1±20,4) and PUCAI (45,3±16 vs 46,2±15,5) scores. Diagnostic delay was longer in patients with genetic conditions compared to controls, without reaching statistical significance (11,1 vs 4,6 months; p= 0,06). Prevalence of comorbidities was significantly higher in group 1 compared to controls both at diagnosis (43,4 vs 11,5%; p &amp;lt;0,005) and at last follow-up (39,1 vs 11,6%; p &amp;lt;0,02). Use of immunosuppressors, steroids and biologic drugs was similar at diagnosis and at last follow-up in the 2 groups. More IBD patients in group 1 developed side effects related to immunosuppressors (26 vs 4%; p &amp;lt; 0,02), while no difference was observed in biologics-related side effects. The need of surgery was comparable in the 2 groups (13 vs 13,9 %), whereas mortality was slightly higher in patients with IBD and genetic syndrome (13 vs 7%). Conclusion In pediatric IBD patients the presence of genetic syndromes does not significantly modify the course of the disease itself, but increases complexity due to the multiple comorbidities and immunosoppressive drug toxicity.

D-ECCO Grant Personalizing the dietetic strategy in children with IBD: exploring an antioxidant approach

Abstract Background and Aims Diet is a key element in the pathogenesis and treatment of Inflammatory Bowel Disease (IBD). Also, oxidative stress (OS) is involved in IBD onset and evolution. Our group is conducting a multicenter trial (the OxIBDiet study, NCT0451301) to explore the OS imbalance in both children and adults with IBD, compared to matched controls, the genetic variants of genes implicated in OS and the effects of an Antioxidant diet (AoD) on these patients. Preliminary results have shown a great imbalance in the total antioxidant capacity in IBD compared to healthy matched controls, particularly in IBD children, and a clear improvement of the antioxidant capacity and oxidant parameters after 3 months of AoD. Aims of this study are: 1. To identify IBD subjects’ responders to a specific dietetic treatment (on the basis of clinical, biochemical and genetic characteristics); 2. To evaluate the effect of antioxidant compounds on stem cell derived 3D models of the intestinal epithelium by organ-on-a-chip technology; 3. To characterize the effect of AoD and Mediterranean diet in terms of inflammatory pattern. Methods A machine-learning algorithm that integrates clinical parameters, anthropometrics, blood parameters and genetic data measured in OxIBDiet cohort will be generated and validated in a new cohort of 30 IBD children (15 CD and 15 UC). Human intestinal organoids will be generated from 10 patients, in which an endoscopy is planned for disease reassessment, and levels of interleukins and TNF-alfa will be measured, after stimulation with antioxidant compounds. Thirdly, cytokine analysis in serum from OxIBDiet cohort who performed dietetic sub-study will be evaluated. Anticipated Impact Results of this study will provide useful indications on factors that influence redox imbalance in IBD and will permit to identify patients who may benefit from a personalized dietetic approach, especially an AoD.

Risk of avoidant/restrictive food intake disorder in patients with inflammatory bowel disease: predictive value of disease phenotype, disease activity and food literacy.

Avoidant/Restrictive Food Intake Disorder (ARFID) is a newly described eating disorder. Adequate levels of food literacy allow individuals to have adequate food choices. This study aimed to assess the prevalence of ARFID and the level of food literacy in patients with inflammatory bowel disease (IBD) and to analyse the correlation between ARFID and food literacy. This cross-sectional study screened for ARFID and assessed food literacy levels in patients with IBD attending four tertiary hospitals in China. ARFID risk was measured using the Nine Item Avoidant/Restrictive Food Intake Disorder Screen (NIAS).Food literacy was assessed using the Food Literacy Evaluation Questionnaire (Chinese version, FLEQ-Ch).The relationship between individual NIAS scores and food literacy variables was analysed to assess which food literacy aspect is positively or negatively associated with NIAS scores. Stepwise linear regression analysis was performed to identify the possible predictors of NIAS scores in patients with IBD. A total of 372 IBD subjects completed the NIAS and FLEQ-Ch. The overall mean NIAS scores for the IBD cohort was 28.16 ± 8.03 (p < 0.01), and of the 372 participants, 123 (32.5%) had positive ARFID risk scores (≥ 10 NIAS-picky eating, ≥ 9 NIAS-poor appetite, and ≥ 10 NIAS-fear of negative consequences).The NIAS scores were inversely associated with food literacy levels (β = - 0.299; p < 0.01).Disease phenotype, disease activity, and food literacy in patients with IBD provided valuable predictive insights for avoiding positive outcomes in ARFID. This study shows that the risk of ARFID in the cohort of patients with IBD is associated with their inadequate food literacy levels. Therefore, this study supports the notion that patients with IBD should be assessed for food literacy regardless of whether they are currently diagnosed with ARFID. Specifically, for early identification of those at risk for ARFID in IBD, disease phenotype, disease activity, and food literacy should be routinely considered in clinical practice.The food literacy awareness of patients must be investigated and improved to predict the risk occurrence of ARFID and encourage healthy eating behaviour.

Mucosal-associated invariant T cells display both pathogenic and protective roles in patients with inflammatory bowel diseases.

An important subtype of the innate-like T lymphocytes is mucosal-associated invariant T (MAIT) cells expressing a semi-invariant T cell receptor α (TCR-α) chain. MAIT cells could be activated mainly by TCR engagement or cytokines. They have been found to have essential roles in various immune mediated. There have been growing preclinical and clinical findings that show an association between MAIT cells and the physiopathology of inflammatory bowel diseases (IBD). Of note, published reports demonstrate contradictory findings regarding the role of MAIT cells in IBD patients. A number of reports suggests a protective effect, whereas others show a pathogenic impact. The present review article aimed to explore and discuss the findings of experimental and clinical investigations evaluating the effects of MAIT cells in IBD subjects and animal models. Findings indicate that MAIT cells could exert opposite effects in the course of IBD, including an anti-inflammatory protective effect of blood circulating MAIT cells and an effector pathogenic effect of colonic MAIT cells. Another important finding is that blood levels of MAIT cells can be considered as a potential biomarker in IBD patients.

Unveiling the Ghrelin and Obestatin Roles in Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis Assessing Their Pathogenic Implications and Biomarker Utility.

Inflammatory bowel disease (IBD), pathologically known as chronic inflammation of the gastrointestinal tract, is among the diseases with a high burden worldwide. Ghrelin and obestatin, as adipocytokines mainly in adipose tissues, are involved in immune responses and inflammatory pathways. Studies have assessed the circulatory ghrelin levels in patients with IBD. Herein, we aim to pool these studies through systematic review and meta-analysis. Four international databases, PubMed, Embase, Scopus, and the Web of Science were systematically searched for studies assessing ghrelin or obestatin levels in patients with IBD (either Crohn's disease [CD] or ulcerative colitis [UC]) in active phase or in remission. Random-effects meta-analysis was conducted in order to calculate the pooled estimate using the standardized mean difference (SMD) and 95% confidence interval (CI). Nineteen studies were included in our systematic review, comprising 1064 patients with IBD (476 UC and 588 CD). A meta-analysis of 11 studies for comparison of active and quiescent disease showed that patients with active IBD had significantly higher levels of ghrelin (SMD, 0.70; 95% CI, 0.06 to 1.34; P = .03). However, in separate analyses for UC or CD, no such difference was observed (SMD, 1.30; 95% CI, -0.28 to 2.88, P = .11; and SMD, 0.80; 95% CI, -0.41 to 2.01; P = .20, respectively). No significant difference was also observed in ghrelin levels between patients with active IBD and healthy control subjects. Obestatin levels also were not different between patients with active disease and those in remission (SMD, 0.31; 95% CI, -0.05 to 0.68; P = .09). On the other hand, the obestatin/ghrelin ratio was significantly lower in patients with active IBD (SMD, -1.90; 95% CI, -2.45 to -1.35; P < .01). Our results demonstrate that IBD patients with active disease have higher levels of ghrelin, which needs to be confirmed in future studies. Also, the obestatin/ghrelin ratio might be a promising biomarker for the assessment of disease activity.

Evaluation of Albumin, Transferrin and Transthyretin in Inflammatory Bowel Disease Patients as Disease Activity and Nutritional Status Biomarkers.

Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is often accompanied by malnutrition that manifests itself as nutrient deficiencies and body mass loss or deficit. The purpose of this study is to evaluate the utility of albumin, transferrin and transthyretin levels in the assessment of nutritional status and IBD activity. The case-control study included 82 IBD patients. The serum concentrations of albumin, transferrin and transthyretine were determined by a quantitative sandwich enzyme-linked immunosorbent assay (ELISA). Significantly lower median concentrations of albumin were found in the IBD patients vs. controls and in CD patients compared to the UC patients. Significantly higher median transthyretin concentrations were found in the IBD patients compared to the healthy subjects. There were no significant differences in median transferrin concentrations between the IBD patients and the healthy subjects. Significantly higher albumin levels were found in IBD patients in remission compared to patients with moderate and severe exacerbation of IBD symptoms. There were no significant differences in the median transferrin or transthyretin levels in patients with IBD depending on disease activity. No differences were identified in the median transferrin or transthyretin levels in the IBD patients according to nutritional status. The median albumin concentrations in the IBD subjects were significantly higher in patients with normal body fat, normal BMI and normal waist circumferences compared to those with an abnormal nutritional status. The albumin levels reflect both nutritional status and disease activity and therefore cannot be considered a prognostic marker of malnutrition in IBD. As regards the utility of transferrin and transthyretin as markers of activity and nutritional status in IBD patients, further studies are required.

Individual and Group-Based Effects of In Vitro Fiber Interventions on the Fecal Microbiota.

The development of microbiome-targeted strategies is limited by individual differences in gut microbiome composition and metabolic responses to interventions. In vitro models that can replicate this variation allow us to conduct pre-clinical studies and assess efficacy. This study describes the exposure of 16 individual fecal microbiota samples to 5 different fibers using an in vitro system for the anaerobic cultivation of bacteria. The individual microbiota differed in composition and metabolite profiles (short-chain fatty acids and branched-chain fatty acids) after incubation with the fibers. Furthermore, microbiota composition after fiber incubation was significantly different between subjects with good intestinal health and subjects with Inflammatory Bowel Disease (IBD). α-diversity was differently affected by dietary fibers; for example, exposure to psyllium resulted in increased diversity in the healthy group and in decreased diversity in the IBD group. Instead, the functional metabolic profile did not differ between the two groups. Finally, the combination of all fibers, tested on the microbiota from IBD subjects, resulted in stronger overall effects on both microbiota composition and metabolite production compared to the single fibers. These results confirm that incubation with dietary fiber results in different compositional and functional effects on individual microbiota and that in vitro models represent successful tools for studying individual fiber effects.

The role of neurotransmitters in mediating the relationship between brain alterations and depressive symptoms in patients with inflammatory bowel disease.

A growing body of evidence from neuroimaging studies suggests that inflammatory bowel disease (IBD) is associated with functional and structural alterations in the central nervous system and that it has a potential link to emotional symptoms, such as anxiety and depression. However, the neurochemical underpinnings of depression symptoms in IBD remain unclear. We hypothesized that changes in cortical gamma-aminobutyric acid (GABA+) and glutamine (Glx) concentrations are related to cortical thickness and resting-state functional connectivity in IBD as compared to healthy controls. To test this, we measured whole-brain cortical thickness and functional connectivity within the medial prefrontal cortex (mPFC), as well as the concentrations of neurotransmitters in the same brain region. We used the edited magnetic resonance spectroscopy (MRS) with the MEGA-PRESS sequence at a 3 T scanner to quantitate the neurotransmitter levels in the mPFC. Subjects with IBD (N = 37) and healthy control subjects (N = 32) were enrolled in the study. Compared with healthy controls, there were significantly decreased GABA+ and Glx concentrations in the mPFC of patients with IBD. The cortical thickness of patients with IBD was thin in two clusters that included the right medial orbitofrontal cortex and the right posterior cingulate cortex. A seed-based functional connectivity analysis indicated that there was higher connectivity of the mPFC with the left precuneus cortex (PC) and the posterior cingulate cortex, and conversely, lower connectivity in the left frontal pole was observed. The functional connectivity between the mPFC and the left PC was negatively correlated with the IBD questionnaire score (r = -0.388, p = 0.018). GABA+ concentrations had a negative correlation with the Hamilton Depression Scale (HAMD) score (r = -0.497, p = 0.002). Glx concentration was negatively correlated with the HAMD score (r = -0.496, p = 0.002) and positively correlated with the Short-Form McGill Pain Questionnaire score (r = 0.330, p = 0.046, uncorrected). There was a significant positive correlation between the ratio of Glx to GABA+ and the HAMD score (r = 0.428, p = 0.008). Mediation analysis revealed that GABA+ significantly mediated the main effect of the relationship between the structural and functional alterations and the severity of depression in patients with IBD. Our study provides initial evidence of neurochemistry that can be used to identify potential mechanisms underlying the modulatory effects of GABA+ on the development of depression in patients with IBD.

Thirty-year Trend in Inflammatory Bowel Disease on Jeju Island, South Korea.

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is increasing in South Korea. On the other hand, there are no reports of the incidence and prevalence of IBD specific to Jeju Island, prompting the necessity of this study. In this retrospective design, the medical records of 453 patients diagnosed with IBD at Jeju National University Hospital from January 1990 to December 2019 were analyzed. Of the 453 IBD subjects (165 CD, 288 UC) included, the UC: CD ratio was 1.75:1. The incidence of IBD increased continuously from 0.19/105 in 1990 to 6.39/105 in 2017 and after that decreased to 4.92/105 in 2019. The male:female ratio was 2.24:1 for CD and 1.29:1 for UC. In the CD subjects, the disease activity included remission (33.3%), mild (25.5%), moderate (30.9%), and severe (6.1%). In UC subjects, the disease activity included remission (24.0%), mild (35.4%), moderate (28.8%), and severe (6.2%). According to the Montreal classification, the cases were as follows: CD: terminal ileum (22.4%), colon (9.7%), ileocolon (66.1%), and upper gastrointestinal involvement (27.3%), and perianal fistula/abscess was present in 43.6% of subjects before or at diagnosis: UC: proctitis (43.4%), left-sided colitis (29.1%), and pancolitis (23.3%) at diagnosis. The incidence of IBD on Jeju Island has increased steadily for approximately 30 years but has exhibited a decline since 2017. Therefore, the incidence of IBD in Jeju is believed to have plateaued. Further study will be needed for clarification.

Results and lessons learned from the sbv IMPROVER metagenomics diagnostics for inflammatory bowel disease challenge

A growing body of evidence links gut microbiota changes with inflammatory bowel disease (IBD), raising the potential benefit of exploiting metagenomics data for non-invasive IBD diagnostics. The sbv IMPROVER metagenomics diagnosis for inflammatory bowel disease challenge investigated computational metagenomics methods for discriminating IBD and nonIBD subjects. Participants in this challenge were given independent training and test metagenomics data from IBD and nonIBD subjects, which could be wither either raw read data (sub-challenge 1, SC1) or processed Taxonomy- and Function-based profiles (sub-challenge 2, SC2). A total of 81 anonymized submissions were received between September 2019 and March 2020. Most participants’ predictions performed better than random predictions in classifying IBD versus nonIBD, Ulcerative Colitis (UC) versus nonIBD, and Crohn’s Disease (CD) versus nonIBD. However, discrimination between UC and CD remains challenging, with the classification quality similar to the set of random predictions. We analyzed the class prediction accuracy, the metagenomics features by the teams, and computational methods used. These results will be openly shared with the scientific community to help advance IBD research and illustrate the application of a range of computational methodologies for effective metagenomic classification.

P838 Increased Risk of Avascular Necrosis in Patients With Inflammatory Bowel Disease: a nationwide population based cohort study

Abstract Background Avascular necrosis (AVN) is bone death due to disruption of blood supply causing disability and significant morbidity. Although considered multi-factorial, corticosteroid use is a well-known risk factor. Not only is AVN more prevalent in Inflammatory bowel disease (IBD), but IBD patients are often exposed to higher corticosteroids usage. Therefore, we aimed to investigate epidemiology and risk factors of avascular necrosis in Asian IBD patients. Methods We conducted a nationwide population-based cohort using Korean National Health Insurance Service (NHIS) database from January 2007 to December 2020. Newly diagnosed IBD patients were defined according to the International Classification of Diseases, 10th revision (ICD-10), and at least one prescription of IBD-specific medications. 1:3 sex-, age- matched subjects from the general population were selected. We investigated newly diagnosed AVN using the ICD-10 code and the incidence rates and risk of AVN were assessed with multivariate cox regression models. Results A total of 62,417 IBD population was identified, where ulcerative colitis (UC) comprised of 44,106. Age at diagnosis was younger in Crohn's disease (CD) than in UC (30±15 years and 43±16.3 years). UC population revealed greater number of comorbidities such as hypertension (16.7% and 7.1% for UC and CD, respectively), diabetes mellitus (12.4% and 9.5%), dyslipidemia (27.6% and 25.2%), and cerebrovascular diseases (4.5% and 2.5%). During the mean follow-up period of 6.75 years, 54,591 (87.5%) of the total IBD patients were exposed to systemic steroids (86.4% and 90.1% for UC and CD, respectively). Approximately 76.8% in the IBD group were prescribed with ≥10 mg/day of corticosteroids with mean duration of 16.3±35.1 days. A total of 100 (0.16%) newly diagnosed AVN cases were observed in the IBD population. Time from the index date to AVN diagnosis was 4.47±3.29 years. Compared to the non-IBD controls, the incidence of AVN was significantly increased in IBD subjects (adjusted hazard ratio [aHR] with 95% confidence interval [CI], 1.28 [1.01-1.63]). UC patients in particular were at an elevated risk for developing AVN (aHR with 95% CI, 1.39 [1.07-1.80]), whereas risk analysis for CD patients demonstrated results that were statistically not significant (aHR with 95% CI, 1.00 [0.63-1.57]). Table 1 Incidence rates and risk ratios of AVN in patients with IBD Conclusion Risk of AVN was elevated in Korean IBD patients compared to non-IBD population, especially for UC. Physicians dealing with IBD patients should be aware of etiological factors of AVN along with corticosteroid use. Future study is needed to investigate on the mechanisms associated with AVN in IBD.

DOP50 Impact of Inflammatory Bowel Disease associated dysbiosis on bacterial quorum sensing mediated by Acyl-homoserine Lactone in human gut microbiota

Abstract Background Intestinal dysbiosis is a key feature in the pathogenesis of inflammatory bowel diseases (IBD). Bacterial quorum sensing mediated by acyl-homoserine lactones (AHL) might play a role in the dialogue between the gut microbiota and the host. The main objective of our study was to investigate the presence and expression of AHL synthase and receptor genes in the human gut ecosystem during IBD. Methods To confirm the presence of AHL in the gut, mass spectrometric detection was performed on stool samples from IBD patients and non-IBD subjects. Then, by an in silico approach, we exploited the open access database: Inflammatory Bowel Disease Multi’omics Database, an American cohort with bacterial metagenomes and metatranscriptomes data of stool samples from non-IBD and IBD subjects. To characterise gut dysbiosis, the most discriminating bacterial species between non-IBD and IBD patients were identified by multivariate analysis and allowed us to define two groups (dysbiosis/non-dysbiosis). The search for AHL synthase (luxI) and receptor (luxR) known homolog genes, was performed using Basic Local Alignment Search Tool (BLAST) from previously assembled gene files (presence/absence) as well as raw data sequencing files (relative abundance and expression). Results Mass spectrometry confirmed a higher concentration of AHL molecules in healthy subjects than in relapsing IBD. Regarding in silico analysis, 103 subjects were selected including 50 with Crohn’s disease (CD), 27 with ulcerative colitis (UC), and 26 non-IBD subjects. No luxI-like synthase genes were retrieved by BLAST searches. However, several homologs of receptor genes were identified: sdiA gene from Escherichia coli (7/103 patients) and luxR-like homologs from Bacteroides fragilis and Bacteroides dorei present in all patients. According to disease, only one luxR-like gene from Bacteroides dorei was under-expressed in IBD patients (p = 0.02) compared to non-IBD, especially in CD (p = 0.02) (Figure 1). In dysbiosis situation, one luxR receptor gene from Bacteroides fragilis appeared to be over-expressed (p = 0.04) compared to non-dysbiotic patients (Figure 2). Conclusion Through this computational approach, AHL-synthesising bacteria have not been found. However, the expression of quorum sensing receptor genes appears to be modulated by IBD-associated gut dysbiosis. The role of LuxR receptors, especially in Bacteroides species, should be investigated to understand its impact on gut microbiota (Figure 3). Targeting LuxR receptors of bacterial quorum sensing might represent a new approach to modulate the gut microbiota in IBD.

WHICH IS IMPORTANT? GLUTEN FREE DIET OR INFLAMMATORY BOWEL DISEASE MEDICATIONS IN SUBJECTS WITH AN OVERLAP WITH CELIAC DISEASE AND INFLAMMATORY BOWEL DISEASE: OBSERVATIONS FROM A CASE SERIES AT A LARGE ACADEMIC CENTER

Abstract INTRODUCTION Celiac disease (CeD) and inflammatory bowel disease (IBD) are autoimmune diseases of the bowel with similar clinical symptoms. This study aims to characterize the clinical course of both diseases in subjects with overlap of CeD and IBD (CeD+IBD) on a gluten free diet (GFD) and IBD medications. METHODS We conducted a retrospective study of demographic and serological characteristics in subjects with CeD+ IBD at a large academic center using appropriate International Classification of Disease (ICD)-10 codes from 2017 to June 2022. RESULTS 36 subjects had IBD +CeD. 96% of subjects were Caucasian and 67% were female. The diagnosis of CeD post-dated the diagnosis of IBD by 3.6 years. Ulcerative colitis (UC) and Crohn’s disease (CD) occurred equally in IBD +CeD. About 75% of subjects had L2+L3, B1 phenotype per Montreal classification. 44% of UC +CeD subjects had pancolitis with 72% of them being classified as S0 (never severe) per Paris classification. 83% of subjects initiated a self-taught GFD. Only 17% of subjects sough advice from a celiac dietician. Mean duration at which GFD was initiated was 0.7 yrs from the initial diagnosis of CeD. Only 1/36 subjects followed a strict GFD during 6.5 years of follow up. The second and third assessment of GFD happened after a mean of 3.7 yrs and 5.2 yrs from the time of initiation of a GFD with only 1/36 subjects adhering to a strict GFD at these time points. Serum tTG IgA levels were tested on average at 4, 91, 154, 186 and 192 weeks from the diagnosis of CeD, with a consistent drop in mean tTG IgA titers to 45, 33, 19, 25 and 4 respectively. Only 1 subject got tTG IgA measurements over the next 250 weeks of follow up. Over a 10.1 year follow up since the diagnosis of IBD, descending proportions of subjects needing IBD medications were as follows: topical 5-ASA (aminosalicyates) (19/36)&amp;gt;oral steroids (18/36)&amp;gt; anti-TNF (tumor necrosis factor) (18/36)&amp;gt; anti-integrins (12/36)&amp;gt; azathioprine (10/36)&amp;gt; anti-IL12/23 (8/36)&amp;gt; topical 5-ASA (4/36)&amp;gt; MTX (methotrexate) (5/36)&amp;gt; topical steroids at 2/36. Mean time to initiation of IBD medications (in weeks) after GFD initiation as a reference point were in an order of oral 5-ASA (-67) &amp;lt; anti-TNF (-39) &amp;lt; AZA (-14) &amp;lt;MTX (-6) &amp;lt; topical 5-ASA (-2) &amp;lt;oral steroids (82) &amp;lt;anti-integrins (124) &amp;lt;anti-IL 12/23 (137) CONCLUSIONS Majority of subjects depended on a self-educated GFD. A small proportion of CeD +IBD subjects were assessed per clinical guidelines with respect to adherence to a GFD, serology. At least 50% of subjects with CeD+IBD needed escalation of IBD treatment to biologics and/or steroid rescue over 10 years despite initiation of GFD (albeit suboptimal). We need to further substantiate these findings with exclusive IBD and celiac control groups. We suggest establishing CeD centers at tertiary hospitals for adequate clinical guideline adherence.

Flagellin-specific human CAR Tregs for immune regulation in IBD

Regulatory T cell (Treg) therapy is a promising strategy to treat inflammatory bowel disease (IBD). Data from animal models has shown that Tregs specific for intestinal antigens are more potent than polyclonal Tregs at inhibiting colitis. Flagellins, the major structural proteins of bacterial flagella, are immunogenic antigens frequently targeted in IBD subjects, leading to the hypothesis that flagellin-specific Tregs could be an effective cell therapy for IBD. We developed a novel chimeric antigen receptor (CAR) specific for flagellin derived from Escherichia coli H18 (FliC). We used this CAR to confer FliC-specificity to human Tregs and investigated their therapeutic potential. FliC-CAR Tregs were activated by recombinant FliC protein but not a control flagellin protein, demonstrating CAR specificity and functionality. In a humanized mouse model, expression of the FliC-CAR drove preferential migration to the colon and expression of the activation marker PD1. In the presence of recombinant FliC protein in vitro, FliC-CAR Tregs were significantly more suppressive than control Tregs and promoted the establishment of colon-derived epithelial cell monolayers. These results demonstrate the potential of FliC-CAR Tregs to treat IBD and more broadly show the therapeutic potential of CARs targeting microbial-derived antigens.

Periodontitis prevalence and severity in inflammatory bowel disease: A case-control study.

Recent evidence is supporting the notion of a microbiological and immunological continuum on the gum-gut axis in health and disease. Therefore, the purpose of this study was to assess the prevalence and risk indicators of periodontitis in patients with Crohn's disease (CD) or ulcerative colitis (UC) compared to age- and sex-matched controls without inflammatory bowel disease (IBD). A total of 180 IBD (117 CD, 60 UC, 3 IBD-unclassified) and 180 healthy controls were compared for their periodontitis diagnosis (Centers for Disease Control and Prevention/American Academy of Periodontology [CDC/AAP] case definition) and full-mouth periodontal parameters. In addition, explorative logistic regression models were performed. Significantly more patients with IBD had moderate/severe periodontitis (85.6% vs. 65.6%, p<0.001) and severe periodontitis (36.7% vs. 25.6%, p<0.001) than controls. Differences were higher in the 35-50 and 51-65 age groups, without significant changes between CD and UC. IBD subjects presented chances ∼3.5 higher of having moderate/severe periodontitis (p<0.001). Significant variables associated with periodontitis in the whole sample were older age, presence of IBD, and higher full-mouth plaque scores, whereas in the IBD group they were male sex, IBD-associated surgery, and IBD duration and localization (pancolitis). Positive risk indicators for IBD were periodontitis severity and higher bleeding scores, while smoking was negatively associated with UC. Relevant associations between IBD and periodontitis were found, being modified by CD and UC clinical characteristics. Preventive and therapeutic strategies involving the gum-gut axis should be enforced in IBD patients.

Higher Cell-Mediated Immune Responses in Patients With Inflammatory Bowel Disease on Anti-TNF Therapy After COVID-19 Vaccination.

BackgroundSome patients with inflammatory bowel disease (IBD) on immunosuppressive therapies may have a blunted response to certain vaccines, including the messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccines. However, few studies have evaluated the cell-mediated immune response (CMIR), which is critical to host defense after COVID-19 infection. The aim of this study was to evaluate the humoral immune response and CMIR after mRNA COVID-19 vaccination in patients with IBD.MethodsThis prospective study (HERCULES [HumoRal and CellULar initial and Sustained immunogenicity in patients with IBD] study) evaluated humoral immune response and CMIR after completion of 2 doses of mRNA COVID-19 vaccines in 158 IBD patients and 20 healthy control (HC) subjects. The primary outcome was the CMIR to mRNA COVID-19 vaccines in patients with IBD. The secondary outcomes were a comparison of (1) the CMIR in patients with IBD and HC subjects, (2) CMIR and humoral immune response in all participants, and (3) correlation between CMIR and humoral immune response.ResultsThe majority (89%) of patients with IBD developed a CMIR, which was not different vs HC subjects (94%) (P = .6667). There was no significant difference (P = .5488) in CMIR between immunocompetent (median 255 [interquartile range, 146-958] spike T cells per million peripheral blood mononuclear cells) and immunosuppressed patients (median 377 [interquartile range, 123-1440]). There was no correlation between humoral and cell-mediated immunity after vaccination (P = .5215). In univariable analysis, anti-tumor necrosis factor therapy was associated with a higher CMIRs (P = .02) and confirmed in a multivariable model (P = .02). No other variables were associated with CMIR.ConclusionsMost patients with IBD achieved CMIR to a COVID-19 vaccine. Future studies are needed evaluating sustained CMIR and clinical outcomes.

Peripartum Infections Among Women With Inflammatory Bowel Disease.

Pregnant patients with inflammatory bowel diseases (IBDs) are frequently treated with immunomodulatory agents and may be at increased risk of adverse outcomes, including peripartum infections. We sought to examine the risk for peripartum infections in patients with IBD compared with control subjects and identify potential risk factors associated with peripartum infections in these patients. This retrospective cohort study compared peripartum infection rates and associated risk factors between pregnant women with and without IBD. The study population included women attending a dedicated joint maternal-fetal medicine and gastroenterology clinic for pregnant women with IBD between 2012 and 2019 at the Rabin Medical Center in Israel, a major referral center for patients with IBD. For each patient, 5 women without IBD were matched according to the newborn's birth date (±2 years), age, parity, and body mass index. Peripartum infection was defined as any 1 of the following: chorioamnionitis, maternal fever (>38°C) detected during labor or postpartum hospitalization, and positive culture taken during the hospitalization. Overall, 195 pregnant women with IBD (72 [37%] with ulcerative colitis, 123 [63%] with Crohn's disease) were matched with 888 control subjects. The mean disease duration was 8.4 ± 7.02 years. IBD therapy, used by 81%, included most frequently 5-aminosalicylic acid (44%) and tumor necrosis factor inhibitors (27%). Peripartum infections were observed in 15 (7.7%) patients and 49 (5.5%) control subjects (P = 1.00). No medication significantly increased the likelihood of peripartum infection. Cesarean delivery was more likely among women with IBD but was not associated with an increased risk of peripartum infection. Peripartum infections were comparable in patients with IBD and control subjects. These reassuring data augment existing knowledge of obstetrical outcomes in IBD patients and contribute to the discussion between caregivers and patients.

Bone Alterations in Inflammatory Bowel Diseases: Role of Osteoprotegerin.

Metabolic bone disorders are one of the most frequent extra-intestinal manifestations in patients with inflammatory bowel diseases (IBD) that might result in an increase of skeletal fragility and risk of fracture. These disorders are a consequence of bone–gut crosstalk alterations, particularly due to inflammation, which involves the RANK-RANKL-Osteoprotegerin (OPG) pathway. This cross-sectional study investigates the role of serum OPG on bone health in IBD patients. In all patients, we carried out BMD measurements at the lumbar spine and femoral neck by the dual-energy X-ray absorptiometry (DXA), and evaluation of serum OPG, 25(OH)D, and PTH. We also divided all IBD patients into two groups: group 1 consisted of premenopausal women and men younger than 50 years old, while group 2 included postmenopausal women and men aged more than 50 years old. We enrolled 36 UC patients (51%), 34 CD patients (49%), and 70 healthy controls. IBD group mean age was 44 ± 17.3 years old, with a mean disease duration of 6 years. IBD patients had a mean value of OPG of 48.1 ± 26.64 pg/mL, while mean OPG in the control group was 61.35 ± 47.19 pg/mL (p < 0.05). In group 1, there was a correlation between BMD Z-scores at the lumbar spine and femoral neck and mean OPG levels in UC subjects (r = 0.47 and r = −0.21, respectively; p < 0.05), and only between Z-score at the lumbar spine and OPG level in the CD group (r = 0.83, p < 0.05). For the patients of group 2, we report a statistically significant correlation between T-score measured at the lumbar site in both UC and CD patients (r = −0.79 and r = 0.77, respectively; p < 0.05). In our study, we demonstrated serum OPG levels to be significantly decreased in IBD subjects compared to healthy age-matched individuals. However, according to our data, it seems that the measurement of serum OPG levels is not useful to better define metabolic bone disorders in IBD patients.