Introduction

Recent scientific literature has supported the novel concept of a non-biopsy approach for the diagnosis of Coeliac Disease (CD) ¹. The AGA guidelines state that symptomatic or at risk patients can avoid a diagnostic biopsy if two separate blood samples demonstrate an anti IgA tissue transglutaminase (IgA-TTG) level of greater than 10 times the upper limit of normal (> 10xULN), in addition to a positive endomysial antibody (EMA) test ².
EMA testing has historically proven to be a critical component of the diagnosis of CD. It is a fluorescence based test using primate oesophagus ². While it has a very high specificity, it is expensive, labour intensive and subject to interpretation bias ². A recent Israeli study by Ben-Tov et al ³ has shown that all patients with an index anti TTG > 10xULN had a positive EMA test within 2 months. This calls into question the usefulness of an expensive and ethically charged testing modality.

Aims & Methods

We aimed to assess the additional diagnostic benefit, if any, of EMA testing in the diagnosis of CD by correlating EMA test results with varying degrees of anti TTG positivity. Our lab is the sole provider of EMA testing for the West of Ireland, serving a population of over 0.5 million. All newly identified positive anti TTG samples with a titre of 5IU/ml and above (EIA Celikey ,Phadia 0-7IU/ml=negative, 7-10IU/ml=equivocal and >10IU/ml =positive) are referred for EMA testing. Over 90% of anti TTG tests carried out at our centre and our affiliates originate from primary care. Data on EMA and anti TTG between January 2019 and December 2024 was included.

Results

Between 2019-2024 our laboratory tested 1,654 newly identified positive anti TTG samples for EMA. 54% (n=893) of samples originated in our own laboratory and 46% (n=761) were referred from other hospital laboratories within our group.
20% (n=333) of the cohort had a TTG value <10 IU/ml and 23% (n=387) had a TTG >100 IU/ml.
Results are presented in Table 1.

TTG value IU/ml	EMA NEGATIVE	EMA WEAKLY POSITIVE	EMA POSITIVE
< 10	63% (210)	32% (107)	5% (16)
10 to 20	20% (7)	44% (168)	36% (135)
20 to 50	2% (7)	12% (39)	86% (286)
50 to 60	0%	0%	100% (69)
60 to 70	2% (1)	0%	98% (48)
70 to 80	0%	0%	100% (32)
80 to 90	0%	0%	100% (39)
90 to 100	0%	0%	100% (34)
>100	0%	0%	100% (387)

Table 1 shows that 99.8% of samples with an anti TTG of > 50 IU/ml had a positive EMA with reducing rates of EMA positivity for lower anti TTG titres.

Conclusion

100% of cases (n=492) where TTG > 10xULN had a positive EMA. This was irrespective of whether the upper limit of normal was considered as the upper limit of positivity (anti TTG >100IU/ml) or the upper limit of equivalency (anti TTG >70IU/ml). EMA testing offers little additional diagnostic benefit for the cohort of patients that are eligible for a non biopsy CD diagnosis. It’s use maybe better reserved for those with low level anti TTG test results.

References

1. Wieser H, Soldaini C, Ciacci C. Non-biopsy Strategy for the Diagnosis of Celiac Disease in Adults: A Narrative Review. Turk J Gastroenterol. 2024;35(8):589-598. doi:10.5152/tjg.2024.24092
2. Husby S, Murray JA, Katzka DA. AGA Clinical Practice Update on Diagnosis and Monitoring of Celiac Disease-Changing Utility of Serology and Histologic Measures: Expert Review. Gastroenterology. 2019;156(4):885-889. doi:10.1053/j.gastro.2018.12.010
3. Ben-Tov A, Achler T, Fayngor R, et al. Endomysial antibodies or anti-tissue transglutaminase type 2 IgA antibodies as a confirmatory test in children with celiac disease. J Pediatr Gastroenterol Nutr. 2025;80(1):147-150. doi:10.1002/jpn3.12383

Introduction

Gastric visceral hypersensitivity (VH) is a key pathophysiological feature of functional dyspepsia (FD), characterized by enhanced perception of gastric distension and postprandial pain. Recent studies suggest that dietary gluten may act as a pro-nociceptive factor in FD, particularly in individuals without celiac disease but with dyspeptic symptoms. However, mechanisms linking gluten to VH remain elusive.

Aims & Methods

In the clinical arm, multiple linear regression assessed associations between gluten intake and symptom frequency/severity (postprandial fullness, epigastric pain, early satiety), adjusting for age, sex, and BMI. In the experimental arm, Sprague-Dawley rats received either a 20% gluten diet or gluten-free diet for 8 weeks; an iodoacetamide-induced FD model served as a positive control. Gastric sensitivity was evaluated by abdominal withdrawal reflex (AWR) and electromyography (EMG) following surgical placement of a gastric balloon and electrodes. Duodenal and fecal samples were collected for 16S rRNA microbiota profiling and RNA-seq. Histological and molecular analyses included H&E staining, intraepithelial lymphocyte (IEL) counts, RT-qPCR of cytokines, and quantification of GFAP, Substance P, and MAPK components by RT-qPCR, Western blot, or immunofluorescence. Aprepitant (10 mg/kg/day) was administered during the final 2 weeks to assess its therapeutic effect.

Results

A total of 74 patients diagnosed with FD based on Rome IV criteria (EPS (epigastric pain syndrome)+PDS (postprandial distress syndrome): 29, EPS: 12, PDS: 33) and 29 healthy controls were included. FD patients, particularly EPS subtypes, exhibited significantly higher gluten intake than healthy controls (P＜0.001). Multiple linear regression revealed that gluten intake was a significant positive predictor of symptom frequency and severity in FD patients (frequency: β = 0.0407, 95% CI: 0.0197–0.0617, P ＜0.001; severity: β = 0.0230, 95% CI: 0.0091–0.0368, P＜0.01).
In rats, gastric sensitivity in the 20% gluten group was comparable to the iodoacetamide-induced FD model and significantly greater than the gluten-free control group, exhibited by slower weight gain, increased AWR score, higher area under the curve (AUC) of electromyograph and reduced 24-hour food intake. Compared to controls, gluten-fed rats showed reduced fecal abundance of Lactobacillus and Lactococcus, increased Lachnoclostridium, and decreased Lactococcus in duodenal mucosa. Duodenal tissues also exhibited elevated intraepithelial lymphocyte (IEL) counts, increased expression of IL-1β, IL-4, and IL-5, and upregulation of inflammation-related genes Reg1α and Reg3β, indicating low-grade mucosal inflammation. In addition, gluten exposure significantly increased duodenal expression of Substance P (SP), GFAP, and phosphorylated MAPK pathway proteins.
At week 8, rats in the gluten group were treated with either the NK1R antagonist aprepitant or saline. Aprepitant administration significantly attenuated VH, as shown by reduced AWR scores and EMG AUC compared with the gluten+saline group. Aprepitant also suppressed the expression of IL-1β, IL-4, Reg1α, Reg3β, and MAPK-related genes, suggesting a key role of SP-mediated neuroimmune activation in gluten-induced VH.

Conclusion

Long-term high gluten intake induces gastric hypersensitivity, accompanied by gut dysbiosis, mucosal inflammation, and SP-mediated MAPK signaling. Targeting neuroimmune pathways may offer novel therapeutic strategies for gluten-induced epigastric symptom management.

References

POMENTI S, DEVINSKY J, JODORKOVSKY D. Diet for Functional Gastrointestinal Disorders/Disorders of Gut-Brain Interaction [J]. The Medical clinics of North America, 2022, 106(5): 899-912.
SHAH A, KANG S, TALLEY N J, et al. The duodenal mucosa associated microbiome, visceral sensory function, immune activation and psychological comorbidities in functional gastrointestinal disorders with and without self-reported non-celiac wheat sensitivity [J]. Gut microbes, 2022, 14(1): 2132078.

Introduction

Biomarkers, like stool short-chain fatty acids (SCFA), metabolites by fermented nondigestible carbohydrates and branched-chain fatty acids (BCFA) derived from the metabolism of essential amino acids may allow for objective measurements of IBS biological changes without self-reporting bias. Diets low in FODMAP significantly reduce the abnormal fecal total SCFA in IBS patients, indicating that the diet normalizes the IBS patients’ abnormal fecal SCFA output.

Aims & Methods

By conducting an exploratory analysis, we aimed to measure stool SCFAs/BCFAs level changes in a subgroup of subjects enrolled in an RCT evaluating the efficacy of a Mediterranean version of the Low-FODMAPS diet (MED-LFD) compared to the nutritional recommendations of the British National Institute for Health and Care Excellence (NICE) for managing non-constipation IBS. A subset of 40 (23 MED-LFD & 17 NICE) patients provided stool samples at 3 time points: Before dietary intervention, at the 1st (4 weeks after initiation of intervention for NICE and at the end of phase 2 for MED-LFD), and the 2nd folow-up (FU), 6 months after intervention initiation. We measured symptoms severity using IBS-SSS. Table 1 shows the detailed measurement of the consumed FODMAPs per day assessed using a triple-pass 24-hour dietary recall twice at the two FUs.

Table 1.

	1st Follow-up			2nd Follow-up
FODMAPs, M(IQR)	MED-LFD (N=20)	NICE (N=17)	p	MED-LFD (N=19)	NICE (N=15)	p
Excess fructose, g/meal	0.17 (0.13-0.38)	0.19 (0.11-0.83)	0.563	0.22 (0.11, 0.39)	0.3 (0.2, 0.47)	0.275
Sorbitol, g/meal	0.02 (0.0-0.06)	0.11 (0.01-0.39)	0.021	0.02 (0, 0.08)	0.14 (0.01, 0.28)	0.245
Mannitol, g/meal	0.004 (0.0-0.07)	0.06 (0.01-0.13)	0.077	0.02 (0.01, 0.13)	0.04 (0, 0.09)	0.664
Fructans, g/meal	0.43 (0.33-0.54)	0.63 (0.48-0.7)	0.051	0.54 (0.27, 0.8)	0.73 (0.51, 1.07)	0.080
GOS, g/meal	0.09 (0.07-0.18)	0.21 (0.09-0.36)	0.106	0.14 (0.07, 0.32)	0.23 (0.14, 0.48)	0.171
Total oligosaccharides, g/meal	0.54 (0.39-0.79)	0.85 (0.65-1.1)	0.038	0.7 (0.33, 1.16)	1.08 (0.72, 1.52)	0.050
Total FODMAPs, g/meal	1.36 (1.0- 1.90)	2.51 (1.68-3.42)	0.011	1.54 (1.10-2.62)	2.62 (1.42-3.90)	0.086
Lactose, g/meal	0.04 (0.01-0.56)	1.36 (0.47-2.46)	0.002	0.32 (0.04, 1.15)	0.27 (0.01, 2.39)	0.808

SCFAs/BCFAs were extracted from frozen samples and analyzed using Gas Chromatography/Mass Spectrometry. SCFAs and BCFAs levels were measured in umol/g of stool. A paired/unpaired t-test was performed to illustrate the organic acid changes among and within two groups. In multiple groups comparison, significant differences between means were examined using one-way analysis of variance. A polynomial regression model was used to describe the relation between BCFAs/SCFAs levels change with IBS-SSS change from baseline at the 1st FU.

Results

We detected a significant reduction in the concentrations of total SCFAs and BCFAs in the MED-LFD (-21.4±20 and -0.429±0.882) and the NICE (-9.9±17.7 and -0.819±0.933) groups, respectively, at the 1st FU. At the 2nd FU, similar reductions from the baseline concentration levels were detected in both intervention groups (total SCFAs: -20.2±18.7 in MED-LFD vs. -10.9±7.4 in NICE; total BCFAs: -0.494±0.806 in MED-LFD vs. -0.76±0.83 in NICE). A polynomial association was observed between the changes in IBS-SSS scores and the changes in stool concentrations of BCFAs and SCFAs from baseline to the 1st FU. Specifically, there was a slight upward trend in the difference of BCFA levels, indicating that a decrease in IBS-SSS scores is associated with a reduction in BCFA levels during the 1st follow-up. This trend peaked around an IBS-SSS change of minus 50 points, the cut-off value for clinical response. Beyond this point, this association slightly declines. A similar trend was noted for SCFA level changes, with the peak occurring around an IBS-SSS change of minus 100 points, after which the association diminishes.

Conclusion

SCFA/BCFA stool levels changes from baseline might be an objective measure of successful dietary intervention for IBS

References

1. Ju X, Jiang Z, Ma J, Yang D. Changes in Fecal Short-Chain Fatty Acids in IBS Patients and Effects of Different Interventions: A Systematic Review and Meta-Analysis. Nutrients. 2024;16(11):1727
2. Rossi M, Aggio R, Staudacher HM, et al. Volatile Organic Compounds in Feces Associate With Response to Dietary Intervention in Patients With Irritable Bowel Syndrome. Clin Gastroenterol Hepatol. 2018;16(3):385-391.e1.

Introduction

Gastric vascular ectasias are a common complication of liver cirrhosis and resultant portal hypertension. Traditional therapy with argon plasma coagulation is expensive. Endoscopic band ligation offers a simpler and more cost effective therapy with similar results.

Aims & Methods

Comparison of efficacy of endoscopic band ligation (EBL) with argon plasma coagulation (APC) in the management of bleeding gastric vascular ectasias (GVE).
The study period was from August 2021 to April 2025. It was carried out in the Department of Gastroenterology and Hepatology, Shaikh Zayed Hospital, Lahore, Pakistan. It was a randomized controlled trial.
30 patients of chronic liver disease who had presented with upper gastrointestinal bleeding due to Gastric Vascular Ectasias , as seen on upper GI endoscopy were recruited. All patients were explained procedural details and informed consent was taken. They were then randomly divided into two groups, A & B, of 15 patients each. Patient in group A underwent EBL while those in group B were treated with APC. After initial endoscopic therapy, these patients were followed up at 2 and 4 weeks. Efficacy of therapy was assessed by using clinical parameters (recurrence of bleeding manifest as hematemesis/malaena/both), laboratory parameters (drop in hemoglobin) and endoscopic parameters ( GVE bleed seen after initial therapy).

Results

One patient from both groups was lost to follow up. Four patients, two out of each group passed away before their last endoscopy session.
In group A (EBL), 4 out of the remaining 12 patients (33 %) needed repeat therapy at 4 weeks while 8 patients (66%) showed post banding healing not requiring repeat banding during the study period.
In group B (APC), 5 out of remaining 12 patients (42%) needed repeat therapy at 4 weeks. 7 out of 12 patients (58 %) did not need repeat therapy. There was one episode of GI bleeding in a patient undergoing band ligation which was managed conservatively with PPI and surcralfate. No other significant procedure related side effects were encountered in either groups.

Conclusion

Endoscopic Band Ligation is comparable in efficacy to Argon Plasma Coagulation for management of Gastric Vascular ectasias, offering significant cost benefits and ease of therapy.

References

1-Keohane J, Berro W, Harewood GC, Murray FE, Patchett SE. Band ligation of gastric antral vascular ectasia is a safe and effective endoscopic treatment. Dig Endosc. 2013 Jul;25(4):392-6.
2- Mohan BP, Toy G, Kassab LL, Ponnada S, Chandan S, Parbhu S, Chandna S, Adler DG. Endoscopic band ligation in the treatment of gastric antral vascular ectasia: a systematic review and meta-analysis. Gastrointest Endosc. 2021 Dec;94(6):1021-1029.e10. doi: 10.1016/j.gie.2021.08.017. Epub 2021 Sep 1. PMID: 34480922.

Disclosure

There were no conflicts of interest in the course of this study

Introduction

A considerable proportion of patients with disorders of gut-brain interaction suffer from carbohydrate intolerances. The European Guideline¹ recommends a diagnostic evaluation that combines malabsorption testing using hydrogen breath tests with symptom assessment using the validated aCPQ². This study evaluates 1) the relationship between the severity of abdominal symptoms (pain, nausea, bloating, flatulence, diarrhea) in patients' histories and the results of malabsorption and intolerance testing, and 2) the response to a diet in patients diagnosed with carbohydrate intolerance (positive aCPQ) with or without malabsorption (pos. or neg. breath test).

Aims & Methods

This is a retrospective analysis of 1,139 tests performed between February 2017 and June 2024in 708 patients (62% female; mean age 42 ± 16 years) referred for evaluation of suspected carbohydrate intolerance at the Medical Universities of Graz and Vienna. Malabsorption was evaluated by breath tests (H₂ maximum rise above baseline and area under the curve), and intolerance by the aCPQ after ingestion of 50 g lactose (n=588), 25 g fructose (n=550) or 25 g trehalose (n=1). Symptom intensities over the preceding six months for diarrhea, bloating, nausea, flatulence, and abdominal pain were assessed using the Bowel Disease Questionnaire (BDQ; VAS scale 0–100 mm). 63 patients with intolerance completed a 4- to 12-week diet. Symptoms after the diet were evaluated using identical VAS scales, with symptom intensity assessed within the previous 10 days. The difference between the VAS scores of each symptom (deltaVAS) before and after diet was determined.

Results

625 tests revealed intolerance (pos aCPQ), 373 malabsorption (pos. breath test), 273 tests a combination of intolerance and malabsorption and 414 tests were negative in both tests. In patients with intolerance weak positive correlations were found between each of the five symptoms in the preceding six months and maximum symptom intensity of the respective symptom on the aCPQ (r ranging from 0.17 to 0.31; p<0.001); the strongest correlation was observed for bloating and the weakest for diarrhea. This applied for the lactose and fructose groups. These correlations were present whether or not malabsorption was detected in the breath test. No significant correlation was observed between BDQ symptom severity and breath test results. The table shows symptom severity by VAS scoring before and after diet in patients with aCPQ-diagnosed intolerance: dietary intervention led to a significant improvement in all symptom severities (p>0.001). For all of the five symptoms strong correlations were observed between baseline symptom severity in the preceding 6 months (BDQ) and the extent of symptom improvement after the diet (delta VAS; *p<0.001). Malabsorption detected by breath test did not predict dietary response. Weak positive correlations were noted between aCPQ symptom severity and deltaVAS for nausea (r=0.32; p=0.012) and bloating (r=0.37; p=0.003).

	Pain	Bloating	Flatulence	Diarrhea	Nausea (median, range
VAS (mm) before diet, mean+SD	40+24	52+28	48+28	36+29	24 (0-75)
VAS (mm) after diet, mean+SD	11+18*	19+20*	26+30*	10+17*	0 (0-65)*
Correlation BDQ vs delta VAS	r =0.76*	r=0.79*	r=0.54*	r=0.84*	r=0.83*

Asterisks denote p<0.001 for comparison of VAS before vs. during diet and for correlation

Conclusion

Diagnosis of intolerance using the aCPQ identifies patients who benefit from dietary intervention. Patients who have the most severe baseline symptom history respond the best. Symptom history is a weak predictor of carbohydrate intolerance, and breath tests are not useful for explaining baseline symptom history or guiding treatment.

References

1. Hammer HF et al. European guideline on indications, performance and clinical impact of hydrogen and methane breath tests in adult and pediatric patients: EAGEN, ESNM and ESPGHAN consensus. United European Gastroenterol J. 2022;10:15-40 https://doi.org/10.1002/ueg2.12133
2. Hammer J et al. Carbohydrate induced gastrointestinal symptoms: development and validation of a test-specific symptom questionnaire for an adult population, the Adult Carbohydrate Perception Questionnaire aCPQ. Eur J Gastroenterol Hepatol 2021:32(2):171-177. doi: 10.1097/MEG.0000000000001880.

Introduction

Eosinophilic Esophagitis (EoE) is a clinicopathological disease that requires an integrated assessment combining clinical, endoscopic, and histological findings. Despite this, treatment decisions often remain symptom based. A treat-to-target strategy has recently been proposed to guide EoE management.

Aims & Methods

Retrospective single-center study of EoE patients followed between March 2012 and January 2024, with ≥12 months of follow-up. Clinical, endoscopic, histological data, and complications were assessed using the I-SEE score.

Results

A total of 82 patients with EoE were evaluated [75.6% (n=62) male, mean age 29 ± 13 years], with 37.8% (n=31) diagnosed during childhood. The most frequent symptom was food impaction (74.4%), and atypical symptoms were more common in pediatric patients (p=0.014). At baseline, 55.1% (n=43) presented with a fibrostenotic phenotype, more frequently in adults (p=0.012), and 32.9% (n=27) had moderate-to-severe disease based on the I-SEE score.
During follow-up, 56.1% (n=46) developed complications, most commonly food impaction requiring endoscopy. The presence of a fibrostenotic phenotype on initial endoscopy was a predictor of complications (OR 3.122; 95% CI 1.210–8.055; p=0.019). Both fibrostenotic phenotype (p=0.018) and moderate-to-severe I-SEE scores (p=0.004) were associated with increased need for therapeutic switching.
At 12 months, 50.0% (n=41) were asymptomatic; however, only 12.2% (n=10) had endoscopic healing and 9.8% (n=8) histologic remission. Throughout the study period, the rates of endoscopic and histologic healing remained below 25%.

Conclusion

The authors highlight the clinical dissociation of inflammatory activity and emphasize the importance of endoscopic and histologic healing to prevent disease progression.

References

Dellon, Evan S., et al. "A clinical severity index for eosinophilic esophagitis: development, consensus, and future directions." Journal of Allergy and Clinical Immunology 150.1 (2022): 33-47.