Introduction

Irritable bowel syndrome (IBS) imposes a substantial burden on patients and healthcare systems globally, with diverse gut symptoms. Its pathophysiology involves disorders in gut-brain interaction and gut barrier dysfunction related to diet and stress. Confocal laser endomicroscopy (CLE) can detect barrier dysfunctions in vivo. Multimodal integrative mind-body medicine-based (MBM) therapy, including stress management, exercise, relaxation, and nutrition, may enhance gut barrier function, symptoms and patient well-being.

Aims & Methods

This study aims to screen IBS patients for prevalent and food-induced gut barrier dysfunction via CLE and explore the impact of a multimodal integrative therapy on barrier integrity, IBS-symptom severity, -quality of life and psychological well-being.
Methods: IBS patients (N=119) admitted between 1 February 2021 and 1 July 2023 at a Clinic for Internal and Integrative Medicine for a two-week inpatient stay underwent esophagogastroduodenoscopy with confocal laser endomicroscopy (CLE) and local food challenge (standardized protocol for egg white, soy, milk, yeast or wheat) to test for a primary prevalent (1°CLE+) or secondary food-induced (2°CLE+) duodenal barrier dysfunction – after exclusion of IgE-mediated food allergy and coeliac disease. All IBS patients received a multimodal MBM therapy. Patients with barrier dysfunction were recommended to adhere to an adjuvant preclinically-tested barrier-stabilising therapy with myrrh, chamomile and coffee charcoal (MYRRHINIL INTEST® 3x4 dragées/ day), and exclusion of CLE-identified barrier-disrupting foods until a voluntary follow-up CLE (2^nd CLE). Pre (=1^st CLE) and Post (=2^nd CLE) intervention, IBS-symptom severity (IBS-SSS), IBS-quality of life (IBS-QoL) and psychological well-being via clinically validated questionnaires were additionally assessed.

Results

Of the 119 IBS patients included in the study, 62% (n=74) showed duodenal barrier dysfunction [1°CLE+: n=27 (23%); 2°CLE+: n=47 (39%)]. Of those, N=35 IBS patients (47%) with barrier dysfunction at 1^st CLE returned for a voluntary 2^nd CLE after 6.3 ± 3.0 months [at 1^st CLE: 1°CLE+: n=15 (43%), 2°CLE+: n=20 (57%); n=25 (71%) female; age 42.9 ± 15.4 yrs, diagnosis age 32.1 ± 15.0 yrs; disease duration 11.1 ± 11.2 yrs]. Of returned IBS patients, n=25 (71%) showed an improved gut barrier integrity, of whom 16 (46%) achieved complete stabilisation of the gut barrier (CLE-).
Pre-intervention, IBS patients were clinically characterized by severe IBS symptom severity (IBS-SSS 304.8 ± 83.4), severely impaired IBS-related quality of life (IBS-QoL 42.7 ± 16.6) and concomitant severe level of anxiety and depression (HADS 19.2 ± 7.7), fatigue (MFI-20 66.8 ± 13.1) and perceived stress (PSS-10 31.3 ± 7.7). Post-intervention, patients exhibited significant and clinically relevant (MCID) improvement in all of these clinical outcomes (IBS-SSS p=<.001, IBS-QoL p=<.001, HADS p=<.001, MFI-20 p=<.001, PSS-10 p=0.004), even allowing the severity score level to be reduced from severe to moderate. Patients reported particular improvement in abdominal pain, change in stool frequency and consistency, abdominal cramps and nausea assessed via 5-point Likert scale.

Conclusion

IBS patients have a high prevalence of existing and food-induced duodenal barrier dysfunction (62%). A multimodal integrative therapy showed a stabilisation of the gut barrier in 71% of IBS patients in a 2^nd CLE as well as significant and clinically relevant improvement in IBS-related symptom severity, quality of life and psychological well-being.

References

1) Sperber AD, Bangdiwala SI, Drossman DA, et al. Worldwide Prevalence and Burden of Functional Gastrointestinal Disorders, Results of Rome Foundation Global Study. Gastroenterology. 2021;160(1):99-114.e3. doi:10.1053/j.gastro.2020.04.014
2) Martin CR, Osadchiy V, Kalani A, Mayer EA. The Brain-Gut-Microbiome Axis. Cell Mol Gastroenterol Hepatol. 2018 Apr 12;6(2):133-148. doi: 10.1016/j.jcmgh.2018.04.003.
4) Hanning N, Edwinson AL, Ceuleers H, Peters SA, De Man JG, Hassett LC, De Winter BY, Grover M. Intestinal barrier dysfunction in irritable bowel syndrome: a systematic review. Therap Adv Gastroenterol. 2021 Feb 24;14:1756284821993586. doi: 10.1177/1756284821993586.
5) Fritscher-Ravens A, Pflaum T, Mösinger M, Ruchay Z, Röcken C, Milla PJ, Das M, Böttner M, Wedel T, Schuppan D. Many Patients With Irritable Bowel Syndrome Have Atypical Food Allergies Not Associated With Immunoglobulin E. Gastroenterology. 2019 Jul;157(1):109-118.e5. doi: 10.1053/j.gastro.2019.03.046. Epub 2019 May 15.
6) Fritscher-Ravens A, Schuppan D, Ellrichmann M, Schoch S, Röcken C, Brasch J, Bethge J, Böttner M, Klose J, Milla PJ. Confocal endomicroscopy shows food-associated changes in the intestinal mucosa of patients with irritable bowel syndrome. Gastroenterology. 2014 Nov;147(5):1012-20.e4. doi: 10.1053/j.gastro.2014.07.046. Epub 2014 Jul 30.
7) Rosenthal R. et al. Myrrh exerts barrier-stabilising and –protective effects in HT-29/B6 and Caco-2 intestinal epithelial cells. Int J Colorectal Dis (2016)

Disclosure

Jost Langhorst
Fees and lecturing: Falk Foundation; Repha GmbH biological medicines; Dr. Willmar Schwabe; Medice Arzneimittel, Galapagos Pharma, Takeda Pharmaceutical, Janssen Cilag, Dr. Pfleger Arzneimittel
Research funding: Steigerwald Arzneimittelwerke GmbH, Falk Foundation, TechLab, Inc., Dr. Willmar Schwabe, Repha GmbH biological medicines,
Other financial or non-financial benefits: none
Consulting and expert activities: Medical Publishers Stuttgart; Steigerwald Arzneimittelwerke GmbH; Repha GmbH; Ferring Arzneimittel GmbH; Dr. Willmar Schwabe
Corporate investments: none
Other conflicts of interest: None

Miriam Bittel
Fees and lecturing: Falk Foundation; Weber & Weber GmbH
Research funding: Deutsche Morbus Crohn/Colitis ulcerosa Vereinigung (DCCV)
Other financial or non-financial benefits: none
Consulting and expert activities: Weber & Weber GmbH
Corporate investments: none
Other conflicts of interest: None

The other co-authors: no conflicts of interest

Introduction

The gut microbiota plays a crucial role in the pathogenesis and progression of Crohn’s Disease (CD) by maintaining intestinal homeostasis, supporting metabolic and immune functions, and influencing overall health. An imbalance in the gut microbiota is associated with CD, as disruptions in microbial composition can be further impacted by dietary factors, highlighting the connection between nutrition and gut health.

Aims & Methods

This study aimed to evaluate the gut microbiota composition and its interactions with dietary factors to identify potential opportunities for targeted probiotic interventions in CD management. The study included 53 participants, of whom 20 had CD in remission, 18 had active disease, and 15 were healthy controls. CD activity was evaluated by colonoscopy assessment or by nuclear magnetic resonance scan enterography. All participants aged between 18 and 60 years were assessed using 24-hour dietary recall and gut microbiome profiling through 16S rRNA gene sequencing. Patients had confirmed diagnoses of CD with ileal and/or colonic involvement. The local ethics committee approved this study.

Results

Microbial composition analyses (beta diversity) revealed significant differences between groups. At the Operational Taxonomic Unit (OTU) level, healthy microbiome differed significantly from both remission and active CD patients, with healthy controls showing a more similar microbial composition compared to remission (p = 0.001) and active disease (p = 0.001). In addition, Shannon diversity analyses demonstrated that healthy individuals exhibited significantly higher OTU diversity compared to CD patients, further highlighting the microbial imbalance associated with the disease. Among specific taxa, Eubacterium hallii, a key butyrate producer, was significantly reduced in patients with active CD. This microorganism is integral to intestinal metabolic balance, playing essential roles in energy homeostasis, colonic motility, immunomodulation, and inflammation suppression. Furthermore, E. hallii plays a critical role in bile acid and cholesterol metabolism, highlighting its importance in gut health. Disease severity was associated with changes in microbial abundance, with specific taxa colonizing the gut at higher levels as disease activity increased, including Escherichia coli, Escherichia-Shigella, and taxa from the Enterobacteriaceae, Lachnospirales, and Bacteroides. This growth may be linked to inflammatory processes and intestinal dysbiosis, suggesting a potentially pathogenic role. Furthermore, dietary components such as saccharin, an artificial sweetener, were significantly associated with alterations in microbial composition.

Conclusion

These findings underline the potential for probiotics targeting specific taxa, such as E. hallii, to restore microbial balance and improve clinical outcomes in CD. The study also highlights the impact of dietary components, such as saccharin, in disrupting the gut microbiome, suggesting that certain dietary factors may contribute to microbial imbalance and inflammation in CD. Future research should focus on integrating dietary patterns with probiotic development to optimize gut health and mitigate inflammation in CD patients.

References

1. BOLTE, L. A. et al. Long-term dietary patterns are associated with pro-inflammatory and anti-inflammatory features of the gut microbiome. Gut, p. gutjnl-2020-322670, 2 abr. 2021.
2. FAN, Y.; PEDERSEN, O. Gut microbiota in human metabolic health and disease. Nature Reviews Microbiology, v. 19, n. 1, p. 55–71, 4 jan. 2021.
3. GILL, P. A. et al. The Role of Diet and Gut Microbiota in Regulating Gastrointestinal and Inflammatory Disease. Frontiers in Immunology, v. 13, n. April, p. 1–22, 5 abr. 2022.

Introduction

Celiac disease (CD) is an immune-mediated enteropathy triggered by gluten ingestion in genetically predisposed individuals, characterized by small intestinal inflammation and villous atrophy. Microbial agents such as Helicobacter pylori (H. pylori) may influence autoimmune disorders, including CD, through immune modulation. However, the relationship remains controversial.This study aimed to assess the association between CD and H. pylori infection by comparing the prevalence of H. pylori in patients with and without CD.

Aims & Methods

We conducted a retrospective study from January 2019 to December 2024. Two groups were analyzed: patients with biopsy-confirmed CD and controls without CD who underwent upper endoscopy for dyspeptic or non-specific gastrointestinal symptoms. Exclusion criteria included prior H. pylori eradication, recent use of PPIs, antibiotics, or bismuth compounds, other autoimmune disorders, and incomplete data.

Results

A total of 231 patients were included: 103 with CD (19.4% male, mean age 28.8 ± 12.6 years) and 128 controls (28.1% male, mean age 33.9 ± 11.9 years).
No significant differences were observed in age (p = 0.73) or sex distribution (p = 0.167) between groups.
H. pylori was detected in 67% of CD patients and 50% of controls, with a significantly higher prevalence in the CD group (p = 0.014).

Conclusion

Contrary to some previous reports suggesting a protective effect, this study found a significantly higher prevalence of H. pylori in patients with CD compared to controls.
These findings highlight the need for further investigations into the potential impact of H. pylori on the clinical presentation and management of celiac disease.

Clinical Case Summary

We present the case of a 50-year-old man diagnosed with anti-EJ positive anti-synthetase syndrome in 2020. Two years after the diagnosis, he began experiencing subacute episodes of postprandial abdominal pain, distension, and vomiting. On physical examination, the abdomen was distended, non-tender, and tympanic. Abdominal CT revealed dilatation of small bowel loops without evidence of mechanical obstruction. Endoscopic studies ruled out endoluminal lesions. Given the suspicion of a severe gastrointestinal (GI) motility disorder, a comprehensive motility evaluation was performed. Esophageal manometry revealed absent contractility, gastric emptying scintigraphy was consistent with gastroparesis, and small bowel manometry demonstrated absence of normal migrating motor complexes during fasting and a weak postprandial motor response, findings compatible with a myopathic pattern. A diagnosis of chronic intestinal pseudo-obstruction (CIPO) secondary to autoimmune disease activity was established. The patient’s immunosuppressive therapy was escalated to tofacitinib and supportive treatment with prokinetics (prucalopride), non- absorbable antibiotics for small intestinal bacterial overgrowth and nutritional supplementation, was initiated. The patient showed symptomatic improvement during follow-up, although small bowel dilation persisted on imaging studies. CIPO is the most severe form of GI motility disorder, representing the end stage of various conditions affecting the neuromuscular system of the GI tract (1). Autoimmune diseases are recognized causes of CIPO, with connective tissue disorders being the most frequently documented. The treatment of CIPO involves two main approaches: addressing the underlying disease, in this particular case, through immunosuppression, and providing supportive care to maintain adequate nutrition. A high index of suspicion for severe GI motility disorders is essential to avoid delays in diagnosis and to initiate effective treatment promptly.

References

1. Malagelada C and Alcalá-González LG. Mistakes in chronic intestinal pseudoobstruction and how to avoid them. UEG Education 2024; 24: 12-17.
Pictures from abdominal distention crisis, radiological CT images and manometric tracings, including high-resolution jejunal manometry (small bowel) will be presented.

Introduction

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly referred to as non-alcoholic fatty liver disease (NAFLD), and dyslipidemia are among the most common metabolic disorders worldwide. Disruption of intestinal barrier integrity, as reflected by elevated zonulin levels, has been implicated in insulin resistance and lipid metabolism disorders, contributing to the pathogenesis of MASLD.

Aims & Methods

The aim was to evaluate fecal zonulin levels in patients with dyslipidemia and MASLD, and to explore their potential role as risk factors for disease development and progression. The study included 342 patients with dyslipidemia, among whom MASLD was diagnosed in 152 cases based on ultrasound and steatometry findings. Fecal zonulin levels were measured by ELISA. Small intestinal bacterial overgrowth (SIBO) was diagnosed using hydrogen breath testing. Correlations between zonulin, inflammatory markers (high-sensitivity C-reactive protein, hsCRP), lipid profiles, and SIBO prevalence were analyzed.

Results

SIBO was detected in 45% of patients with dyslipidemia and 53.2% of patients with MASLD. Fecal zonulin levels in patients with MASLD (115±2.76 ng/g) significantly exceeded the normal upper limit (≤107 ng/g) and were higher compared to patients without steatosis. Zonulin levels positively correlated with hsCRP (r=0.65, p<0.05) and triglycerides (r=0.58, p<0.05). A strong negative correlation was observed between SIBO presence and HDL-C levels (r=–0.78, p<0.05) in patients with dyslipidemia.

Conclusion

Elevated zonulin levels and increased intestinal permeability are closely associated with systemic inflammation and lipid metabolism disturbances in MASLD. Zonulin and SIBO may represent novel therapeutic targets for the prevention and treatment of MASLD and metabolic disorders.