Introduction

A third of patients with coeliac disease (CD) fail to induce complete mucosal remission or symptom control despite a strict gluten-free diet (GFD) for 12 months (non-responsive CD; NRCD). Refractory CD (RCD) is a form of complicated NRCD characterised by significant malabsorption and enteropathy and is classified into type 1 (RCD1; normal T cells) and type 2 (RCD2; aberrant T cells). Treatment options are limited; retrospective case series have shown variable benefit of budesonide in NRCD¹ and RCD² and suggest an open capsule format that promotes proximal small intestinal delivery may be superior to closed capsules².

Aims & Methods

To describe the effect of budesonide and its format on mucosal healing, symptoms and tolerability in NRCD and RCD we conducted a retrospective cohort study of CD patients who received budesonide between January 2011 and March 2023 under the care of a CD gastroenterologist. Subjects were identified through a query of medical records. Cases with biopsy-proven CD on a GFD for at least 12 months who received budesonide for persistent enteropathy were examined. All patients had strict adherence to a GFD confirmed by a dietitian. The primary outcome was improvement in histology, assessed by Marsh-Oberhuber classification, with complete recovery defined as regression to Grade 0 or 1, and partial recovery defined as an improvement in Marsh grade. Symptoms and adverse treatment effects were also recorded.

Results

47 patients with NRCD (n=11; 82% F), RCD1 (n=30; 57% F) and RCD2 (n=6; 33% F) were identified, with mean time on GFD 4.6, 12 and 10.3 years and mean age of NRCD/RCD diagnosis 56.0, 58.1 and 58.6 years, respectively. NRCD patients were minimally symptomatic, while common symptoms in RCD1 and 2 were diarrhoea (73%) and weight loss (43%). Reduced bone mineral density affected 64% of all participants pre-treatment. A course of closed capsule budesonide (CCB) 9mg OD (n=16) and open capsule budesonide (OCB) 3mg TDS (n=31) was provided most commonly for 3-4 months. Mucosal healing was higher in the OCB cohort - Complete: OCB 16/31 (52%) vs. CCB 1/16 (6%) and Partial: OCB 9/31 (29%) vs. CCB 4/16 (25%). Similarly, symptom improvement was higher in the OCB cohort - Complete: OCB 9/19 (47%) vs. CCB 2/14 (14%) and Partial: OCB 8/19 (42%) vs CCB: 3/14 (21%). Overall, the OCB cohort had significantly greater improvement in mucosal healing (w=105.5, p<0.001) and symptoms (w=55, p=0.003) (Mann-Whitney U test). Side-effects were reported in 10/47 (21%) and included hyperglycaemia, weight gain, insomnia, tremor, dizziness, bruising and oesophageal candidiasis and were generally mild.

Conclusion

OCB was well tolerated and associated with improvements in enteropathy in 81% and symptoms in 89% of NRCD and RCD patients in contrast to lower rates with CCB. Prospective studies are warranted to confirm the efficacy and long-term safety of budesonide delivered to the proximal small bowel in patients with NRCD and RCD.

References

1. Therrien A, Silvester JA, Leonard MM, et al. Enteric-Release Budesonide May Be Useful in the Management of Non-Responsive Celiac Disease. Dig Dis Sci 2021;66:1989-1997.
2. Mukewar SS, Sharma A, Rubio-Tapia A, et al. Open-Capsule Budesonide for Refractory Celiac Disease. Am J Gastroenterol 2017;112:959-967.

Disclosure

This study was funded by a research grant provided by Tillots Pharma.

Introduction

Dysbiosis of gut microbiota has recently been suggested to be implicated in the pathophysiology of functional dyspepsia (FD). However, qualified studies on the gastric microbiota in FD patients are lacking, and it is unclear whether there are differences in gastric microbiota between the subgroups of FD.

Aims & Methods

Our aim of the present study was to compare the diversity and composition of gastric fluid microbiota between postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS) in patients with FD. Eighteen patients with FD who met the Rome IV criteria and 12 age- and gender-matched healthy controls who had no chronically recurrent abdominal symptoms with absence of past or present Helicobacter pylori (HP) infection participated in the study. Gastric fluid was obtained from the subjects after an overnight fast, using a sterilized tube inserted into the stomach through the working channel of the endoscope. DNA was extracted and quantified from the samples. Samples from 15 FD patients (83.3%) and 6 healthy controls (50%) were adequate for analysis. The V3 and V4 region of 16S rRNA gene was amplified and sequenced using the MiSeq™ platform (Illumina, San Diego, USA).

Results

The microbiota diversity indices did not significantly differ in FD patients without HP infection, compared with healthy controls. There were no significant differences in the microbiota diversity and composition at the phylum level between PDS patients and healthy controls, and between EPS patients and healthy controls. At the genus level, the relative abundance of Centipeda was significantly increased in patients with PDS, whereas that of Massilia, Acinetobacter, Enterococcus, Bacteroides, and Blautia was significantly decreased in patients with PDS. In patients with EPS, the relative abundance of Collinsella, Holdemanella and Paraprevotella was significantly increased, whereas that of Massilia was significantly decreased. At the species level, the relative abundance of Prevotella intermedia, Veillonella tobetsuensis, Neisseria subflava, and Centipeda periodontii was significantly increased in patients with PDS. The relative abundance of Clostridium leptum, Clostridium perfringens, Alistipes ihumii, Collinsella aerofaciens, Eubacterium ventriosum, Holdemanella biformis, Klebsiella aerogenes, Paraprevotella clara, Sphingomonas olei, and Sutterella wadsworthensis was significantly increased in patients with EPS.

Conclusion

Although the diversity of gastric fluid microbiota is not different between PDS and EPS subgroups, there are differences in their composition between PDS and EPS. Further investigation is needed to determine whether those differences in the composition of gastric fluid microbiota are cause or effect.

References

1. Nakae H, et al. Gastric microbiota in the functional dyspepsia patients treated with probiotic yogurt. BMJ Open Gastroenterol. 2016 Sep 16;3(1):e000109.
2. Igarashi M, et al. Alteration in the gastric microbiota and its restoration by probiotics in patients with functional dyspepsia. BMJ Open Gastroenterol. 2017 May 1;4(1):e000144.
3. Tziatzios G, Gkolfakis P, Papanikolaou IS, et al. Gut microbiota dysbiosis in functional dyspepsia. Microorganisms 2020;8:691.

Introduction

Potential celiac disease (PCD) is characterized by a genetic predisposition and positive celiac-specific serology in the absence of villous atrophy, while the patient is on a gluten-containing diet (GCD).
Although progression to overt celiac disease (CD) may occur, the natural history of PCD remains unpredictable, partly due to the early initiation of a gluten-free diet (GFD) in some patients following diagnosis.

Aims & Methods

We included both adult and pediatric patients referred to two tertiary referral centers in Milan between 2006 and 2024.
At the time of presentation, PCD was defined by the presence of positive anti-transglutaminase (anti-tTG) antibodies, genetic predisposition to CD, and absence of villous atrophy on duodenal biopsy.
This retrospective study collected clinical, serological, endoscopic, and histological data at baseline and throughout follow-up.
The aim was to characterize individuals with PCD by describing their clinical and histological features at presentation and identifying potential risk factors associated with progression to overt CD

Results

A total of 120 patients (50 children and 70 adults) were included in the study. At baseline, 80% of patients were symptomatic, with the most common complaints being bloating (36.8%), abdominal discomfort (35.1%), and diarrhea (26.1%). The median anti-tTG level was 4.93 times the upper limit of normal (95% CI: 3.63–6.23). Despite this, 25% of upper endoscopies showed macroscopic signs suggestive of atrophy, while histology revealed Marsh 0 in 72.3% and Marsh 1 in 27.7% of cases.
During follow-up, 20 patients developed villous atrophy after a mean interval of 1.3 ± 2.1 years. Cox regression analysis identified higher baseline anti-tTG levels as significantly associated with progression to overt CD (HR 1.78, p = 0.029; 95% CI: 1.06–3.01), independent of age and sex.
The remaining 100 patients did not progress to CD during follow-up, which included repeat serological testing and upper endoscopy. Among them, 18 chose to initiate a gluten-free diet (GFD), with 11 reporting symptomatic improvement. The others continued a gluten-containing diet without symptom worsening.

Conclusion

PCD has been confirmed as a condition distinct from overt CD. Despite prolonged follow-up, only 16% of patients progressed to overt CD, suggesting that the majority of individuals with PCD can safely maintain a gluten-containing diet without developing symptoms or histological damage. Elevated anti-tTG antibody levels at baseline emerged as a significant risk factor for progression to villous atrophy.
In conclusion, most PCD patients can be managed conservatively and monitored over time without the need for immediate dietary restrictions.