Introduction

External factors, including microflora, are thought to trigger Celiac Disease (CeD), explaining why the disease develops later in life in a significant proportion of patients (Galipeau et al., 2015; Nistal et al., 2016; Caminero et al., 2019). Barrier defects secondary to a defective epithelial polarity might add to this process. Our goal was therefore to study the capacity of microorganisms to alter polarity and barrier function in intestinal epithelial cells and to increase transport of gluten peptides across the epithelial barrier.

Aims & Methods

The study was structured in two phases. In phase I (screening), cell lines including Caco2-Bbe and Caco2-PIP2, transfected with a GFP-tagged PIP2 binding moiety to analyze cell polarity, were exposed to microorganisms. Selection of microorganisms was based on four criteria: decrease of transepithelial resistance, impact on tight junction and polarity molecules in confocal microscopy and increase of paracellular permeability in sandwich assays. In phase II, a detailed analysis of the microorganisms selected in phase I was done on monolayers derived from human duodenal organoids from healthy individuals and celiac disease patients. The observations of phase I were confirmed in phase II based on four criteria: decrease of transepithelial resistance, impact on tight junction and polarity molecules, increased gliadin translocation in Sandwich assays and HPLC analyses.

Results

Pseudomonas aeruginosa and Candida albicans were selected in Phase I and showed a decrease of 90% and 95% of the initial TER respectively. Escherichia coli K12 and Saccharomyces cerevisiae were used as negative controls for P. aeruginosa and C. albicans respectively. Phase II is currently being completed on healthy and celiac duodenal organoids monolayers. On healthy organoid monolayers, C. albicans and P. aeruginosa induced a decrease of 80% of the initial TER after 24h and 20h respectively. On celiac organoid monolayers, C. albicans and P. aeruginosa caused a decrease of 80% of the initial TER after 17h and 5h respectively. C. albicans and P. aeruginosa disrupted tight-junctions and polarity proteins on healthy organoids and induced and increase of 33mer paracellular translocation in Sandwich assays on both healthy and celiac organoids.

Conclusion

These results indicate that microorganisms have the capacity to induce a barrier defect in duodenum organoid derived monolayers. Furthermore, the organoids derived from CeD patients appear to be more sensitive to exposure to microorganisms compared to healthy organoids. Further experiments will be conducted to better characterize the impact of these microorganisms on organoids and translocation of gliadin peptides across epithelial barrier.

References

Galipeau H.J, McCarville J. L., Huebener S. et al., Intestinal Microbiota Modulates Gluten-Induced Immunopathology in Humanized Mice, The American Journal of Pathology, Volume 185, Issue 11, 2015, Pages 2969-2982, https://doi.org/10.1016/j.ajpath.2015.07.018.
Nistal E., Caminero A., Herrán A.R. et al., Study of duodenal bacterial communities by 16S rRNA gene analysis in adults with active celiac disease vs non‐celiac disease controls, Journal of Applied Microbiology, Volume 120, Issue 6, 1 June 2016, Pages 1691–1700, https://doi.org/10.1111/jam.13111
Caminero, A., McCarville, J.L., Galipeau, H.J. et al. Duodenal bacterial proteolytic activity determines sensitivity to dietary antigen through protease-activated receptor-2. Nat Commun 10, 1198 (2019). https://doi.org/10.1038/s41467-019-09037-9.

Introduction

Coeliac disease (CeD) is a chronic immune-mediated enteropathy driven by dietary gluten proteins. Previous studies have indicated an increased risk of cardiovascular disease (CVD) in individuals with CeD [1-3]. However, results are inconsistent and specific guidelines on the management of CVD risk and comorbidities for individuals with CeD do not exist. In this study, we aimed to compare the distribution of traditional CVD risk factors in CeD patients and non-CeD controls from a population-based cohort.

Aims & Methods

We performed a CeD screening of 54,541 serum samples by anti-transglutaminase 2 immunoglobulin A and G serology from in total 56,042 adult participants in the fourth wave of the Norwegian Trøndelag Health Study (HUNT4) [4]. All seropositive participants were invited to upper endoscopy with duodenal biopsies to confirm a CeD diagnosis. Seronegative participants with previously diagnosed CeD were identified by linkage to hospital records and the Norwegian Patient Registry. We calculated SCORE2 and SCORE2-OP as predictors for 10-year risk of first-onset CVD [5, 6]. The groups “no CeD”, previously diagnosed CeD (“known CeD”) and CeD diagnosed in HUNT4 (“new CeD”), as well as “CeD” (known + new cases) were examined in this study. To compare group characteristics, we used the Wilcoxon rank sum test. Associations between groups and SCORE2(-OP) were assessed using ordinal logistic regression analysis.

Results

468 (0.80%) individuals received a CeD diagnosis in HUNT4, while 309 (0.57%) seronegative individuals had known CeD. Individuals with newly diagnosed CeD were younger, better educated, and had lower blood lipids compared to controls. Individuals with CeD smoked significantly less, had lower BMI and waist-hip-ratio, glycated hemoglobin levels, serum creatinine, and hsCRP levels compared to controls without CeD (n=52,438; p<0.05 for all variables mentioned, see table). We found a significantly lower SCORE2 for CeD cases (n=589) compared to controls (n=39,747; p<0.05). Adjustment for alcohol consumption did not affect group characteristics. A significantly lower SCORE2 was observed in CeD cases also after adjustment for level of education (OR .84, 95% CI .72-.98), high sensitivity C-reactive protein (hsCRP) and serum creatinine (OR .85, 95% CI .78-.99), but not for the combination of all three variables (OR .90, 95% CI .76-1.05).

Conclusion

Individuals with CeD appear to have a lower cardiovascular risk based on traditional risk factors like smoking habits, body fat, diabetes, renal function and inflammation compared to control individuals without CeD. In line with that, SCORE2 and SCORE2-OP as predictors for 10-year risk of first-onset CVD were lower in individuals with CeD.

References

1. Bathrellou, E., M.D. Kontogianni, and D.B. Panagiotakos, Celiac disease and non-celiac gluten or wheat sensitivity and health in later life: A review. Maturitas, 2018. 112: p. 29-33.
2. Ludvigsson, J.F., et al., Nationwide cohort study of risk of ischemic heart disease in patients with celiac disease. Circulation, 2011. 123(5): p. 483-90.
3. Figtree, G.A., et al., Mortality in STEMI patients without standard modifiable risk factors: a sex-disaggregated analysis of SWEDEHEART registry data. Lancet, 2021. 397(10279): p. 1085-1094.
4. Asvold, B.O., et al., Cohort Profile Update: The HUNT Study, Norway. Int J Epidemiol, 2023. 52(1): p. e80-e91.
5. SCORE2 working group and ESC Cardiovascular risk collaboration, SCORE2 risk prediction algorithms: new models to estimate 10-year risk of cardiovascular disease in Europe. Eur Heart J, 2021. 42(25): p. 2439-2454.
6. SCORE2-OP working group and ESC Cardiovascular risk collaboration, SCORE2-OP risk prediction algorithms: estimating incident cardiovascular event risk in older persons in four geographical risk regions. European Heart Journal, 2021. 42(25): p. 2455-2467.

Disclosure

None.

Introduction

Celiac disease (CD) is a complex multi-systemic autoimmune disease. The present study aims to determine the rate of mucosal recovery and predictors of persistent mucosal damage after GFD. There is still little evidence on the best method for assessing gluten-free diet (GFD) adherence and mucosal recovery during treatment.

Aims & Methods

The retrospective study included only adult patients (age≥18 years old), with biopsy-proven CD evaluated at a tertiary referral centre between 2016-2021.We performed a logistic regression analysis to identify factors associated with partial mucosal recovery (MR) after GFD. We included in the multivariate analysis parameters available at the time of CD diagnosis.

Results

A total of 102 patients were enrolled, two thirds were females, median age of 39 yrs. The initial biopsy analysis showed different stages of villous atrophy (VA) in 79 (77.4%) cases, while 23(22.5%) cases showed mild enteropathy (Marsh 1,2). After at least 12 months of GFD, 26 (25.5%) patients had persistent VA despite good or excellent adherence to GFD. Younger patients (< 35yrs), who showed severe mucosal damage (Marsh 3c lesions) and who had increased anti-gliadin antibody (AGA) levels were at risk for failure to obtain mucosal recovery (MR). The multivariate Cox regression analysis demonstrated that complete mucosal atrophy (p = 0.007) and high AGA antibody levels (p = 0.001) were independent risk factors for a lack of mucosal improvement after at least 12 months of GFD. Interestingly, genotype, tTG-IgA antibody levels, or duration of GFD levels did not influence the occurrence of MR.

Conclusion

Although AGA seropositivity has lost much of their diagnostic significance in recent years due to the introduction of the more sensitive and specific antibody tests, our study reported that patients aged < 35yrs, who showed severe mucosal damage (Marsh 3c lesions) and who had increased AGA antibody levels at diagnosis were at risk for failure to obtain MR. The elevated AGA levels at diagnosis could be used as a prognostic tool for assessing MR.

Disclosure

nothing to disclose

Introduction

Celiac disease is an autoimmune disorder where the intake of gluten (a protein found in wheat, barley, and rye) causes damage to the small intestine and impairs nutrient absorption. Studies have shown that individuals with celiac disease have reduced quality of life and higher levels of anxiety and depression. However, this has not been studied in the general population, among individuals with newly discovered, untreated celiac disease.

Aims & Methods

The aim of this study was to investigate anxiety, depression, mental health, and subjective well-being in individuals with newly diagnosed and untreated celiac disease, compared with the general population. This study used data from the fourth Trøndelag health study (HUNT4), conducted between 2017 and 2019 with over 56,000 adult participants from 20 years of age. Previously undiagnosed celiac disease was identified among the participants by analyses of blood samples from all participants and confirmed with endoscopy and duodenal biopsies. The participants in HUNT4 also answered questionnaires measuring levels of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS), mental distress using the Cohort of Norway Medical Health Index (Conor-MHI), and subjective well-being using a three-part questionnaire. Differences in mental health among individuals with newly diagnosed celiac disease and the remaining HUNT4 participants were compared.

Results

Celiac disease was diagnosed in 454 HUNT4 participants by March 2022. The celiac group had a lower median age (53 vs. 56 years) compared to the remaining HUNT4 population. The celiac group had significantly lower mean scores on the HADS anxiety subscale (4.0 vs. 4.4), depression subscale (2.8 vs. 3.3), and total scale (6.8 vs. 7.7) compared to the reference population. On the CONOR-MHI scale, the celiac disease group had a lower total mean score (1.4 vs. 1.5) with lower scores in the categories of "secure and calm", "irritable", "happy and optimistic", "sad/depressed", and "lonely" compared to the reference population. Finally, the celiac disease group had a lower mean score on the question “Do you feel mostly strong and clear, or tired and fatigued?” (3.3 vs. 3.4) and a higher mean score on the question “How is your health now?” (3.0 vs. 2.9) compared to the reference population. No significant difference was observed in the HADS or CONOR-MHI scores by Marsh grades at diagnosis among the celiac disease group.

Conclusion

The study suggests that individuals with undiagnosed celiac disease have lower levels of anxiety, depression, and mental distress compared to the general population, while also reporting slightly better subjective well-being. These findings contradict other studies on psychological health in celiac disease.

Disclosure

No con

Introduction

Enteroscopy is an established method for endoscopic diagnosis and interventions in the small intestine. Currently, there are three procedures available: single-balloon enteroscopy, double-balloon enteroscopy, and motorized spiral enteroscopy. Recent studies have shown that motorized spiral enteroscopy is very effective but also associated with more complications. There are no comparative studies between double-balloon and motorized spiral enteroscopy.

Aims & Methods

This randomized, prospective trial was conducted at two tertiary centers. All consecutive patients with an indication for enteroscopy were asked to participate in the study. Patients were randomly assigned to the motorized spiral or double-balloon arm after being informed. The examination was then performed with the respective procedure.
This study aims to compare the effectiveness of the new motorized spiral enteroscopy with double-balloon enteroscopy. The time to diagnosis or complete enteroscopy and possible complications of both procedures were investigated.

Results

39 enteroscopies (19 motorized spiral, 20 double-balloon) were performed in 36 patients. In the spiral group, access was achieved orally in 58% of cases. A complete enteroscopy was possible in 26% of cases with a median time of 36 minutes. In 16%, a complete enteroscopy was possible via the oral route. In the double-balloon group, access was achieved orally in 85% of cases. A complete enteroscopy was possible in 10% of cases with a median time of 45 minutes. In 5%, a complete enteroscopy was possible via the oral route. Diagnostic yield was higher in double balloon enteroscopy compared to spiral enteroscopy with positive findings in 75% and 32% respectively. There was one perforation in the motorized spiral group. There were no severe complications in the balloon group.

Conclusion

Motorized spiral enteroscopy seems to be more effective in terms of speed and depth. However, it is also associated with more complications

Introduction

The new nomenclature of Non alcoholic fatty liver disease (NAFLD) as metabolic dysfunction-associated steatotic liver disease (MASLD), has an excellent concordance and 99% of individuals with NAFLD meet MASLD criteria. MASLD is becoming the most rapidly increasing contributor to the disease burden related to adverse liver outcomes, including cirrhosis, liver failure, and HCC. To curb this rising tide of MASLD (38.2% global prevalence), an early comprehensive and efficient management strategies are very crucial. Saroglitazar, a novel dual PPAR α/γ agonist operates through a multifaceted mechanism of action, targeting key pathways driving the progression of MASLD, and have shown benefits at different stages of disease ranging from early to advance fibrosis and compensated cirrhosis.

Aims & Methods

We tried to evaluate the effect of Saroglitazar in MASLD associated early fibrosis, in a population where majority did not have diabetes and hypertension at baseline.
A prospective, real world study was conducted at a single centre setting in North India with 67 patients showing ultrasonographic evidence of fatty liver changes and dyslipidemia. Transient elastography was performed to reliably exclude advanced liver disease and treatment progression at 3 and 6 months after Saroglitazar 4 mg OD prescription. The Controlled Attenuation Parameter (CAP) and liver stiffness measurement (LSM) were assessed as primary treatment endpoints along with other markers of liver function and metabolic health as secondary efficacy parameters. Changes were evaluated using paired t-tests, from baseline to the 12 and 24 week mark. This rigorous methodology allowed for a comprehensive assessment of Saroglitazar's impact on both liver health and metabolic parameters.

Results

The 67 patients, who followed the study inclusion criteria and treated with Saroglitazar 4 mg OD, were evaluated on primary and secondary efficacy parameters. They had the mean age 50.34 ±11.69 and mean body weight 82.1 ±11.9. Among them, 61.2% are males, 88.1% non diabetic, 89.6% non hypertensive, and 83.6% are not having any family history of NAFLD. 57.8% of them had F0-F1 fibrosis and 34.4% had F2 fibrosis at baseline. The mean reduction in CAP was 34.7 (p<0.001) and 38.7 dB/m (p<0.001) and mean reduction in LSM was 0.53 (p=0.043) and 1.31 Kpa (p<0.001), respectively at 12 and 24 weeks (n=32). A significant and consistent reduction in AST, ALT, TG, LDL and HbA1c was also seen. No new safety signals were observed.

Table: Absolute and percentage mean changes in Primary and secondary study parameters at 12 and 24 weeks

Conclusion

Treatment with Saroglitazar 4 mg significantly reduces liver stiffness and steatosis, improves liver enzymes, and other metabolic parameters like serum glucose and lipid profile. It could be a crucial treatment component for an early comprehensive and efficient management of MASLD and helpful in curbing the rising tide of global MASLD burden. Saroglitazar treatment was safe.

References

1. Targher G, Byrne CD, Tilg HMASLD: a systemic metabolic disorder with cardiovascular and malignant complicationsGut 2024;73:691-702.
2. Lei Miao, Giovanni Targher, Christopher D. Byrne, Ying-Ying Cao, Ming-Hua Zheng, Current status and future trends of the global burden of MASLD, Trends in Endocrinology & Metabolism, 2024,ISSN 1043-2760, https://doi.org/10.1016/j.tem.2024.02.007.
3. Soto A, Spongberg C, Martinino A, Giovinazzo F. Exploring the Multifaceted Landscape of MASLD: A Comprehensive Synthesis of Recent Studies, from Pathophysiology to Organoids and Beyond. Biomedicines. 2024; 12(2):397. https://doi.org/10.3390/biomedicines12020397