Introduction

Dietary fiber influences the intestinal mucosa and improves intestinal function. The beneficial role of fiber is thought to be mediated by short chain fatty acids (SCFAs) - the main fermentation products of dietary fiber. Glucagon-like peptide-1 (GLP-1) is known to protect against intestinal injury and mice fed a fiber-free (FF) diet have shown loss of intestinal mass and decreased tissue levels of GLP-1. Here, we aimed to 1) investigate how a FF diet might affect the colonic luminal content of SCFAs 2) investigate ability of SCFAs to drive colonic GLP-1 secretion and 3) assess the impact of a low fiber diet on the colonic vulnerability to intestinal injury. We also aimed to investigate the involvement of the free fatty acid receptors 2 (FFAR2) and 3 (FFAR3) and the GLP-1 receptor (GLP-1R) in a model of intestinal injury.

Aims & Methods

Female C57BL/6JRj mice were fed a FF diet (Altromin 1013), or standard chow diet (Altromin C1310) for 21 days and the SCFA concentrations in colonic contents were analyzed by liquid chromatography–mass spectrometry. A SCFA mix (100 mM) was applied luminally in our isolated perfused colon model and GLP-1 levels were measured in the venous effluent. Female C57BL/6JRj mice fed a FF diet or chow were exposed to 3% dextran sulfate sodium (DSS) in drinking water for up to 7 days to induce colitis. Mice were killed at day 13. This was repeated in FFAR2/3 knock out (KO) mice and in GLP-1R KO mice. Wild type (WT) littermates were used as controls. End points were body weight (BW) loss, disease activity index (DAI), colon weight, colon length and histological severity score.

Results

21 days of FF feeding decreased the concentrations of SCFA in colon content significantly. Overall, the total measured SCFAs were decreased by more than 50% in the FF fed group (p<0.05) with specific decreases in acetate (p<0.05), propionate (p<0.05), and butyrate (p<0.001).
SCFAs delivered to the isolated perfused colon increased GLP-1 secretion by 40% (p<0.01). In the DSS model, the removal of dietary fiber increased the severity of colitis and delayed the recovery. At day 4 FF fed mice had bloody diarrhea and DSS treatment was discontinued. From day 4 to the end of the experiment, FF fed mice had a significantly larger BW loss than chow fed mice (day 7: 25% vs 10%, p<0.001). At day 13 all chow fed mice had recovered their BW, but FF fed still showed a significant BW loss of 15% of baseline BW. DAI was significantly increased in the FF fed mice. Only 50% of the FF fed mice survived to day 13 whereas all mice fed chow survived. At day 13 colonic weight was increased (p<0.001), colonic length decreased (p<0.05) and histological severity score increased (p<0.001) in the FF fed mice. GLP-1 KO mice exposed to DSS had a significant larger BW loss from day 10 to day 13 day compared to WT (p<0.05). WT mice recovered their BW to normal at the end of experiment, whereas GLP-1R KO mice had a weight loss of 8% of baseline BW. No other parameters in the GLP-1R KO mice differed from WT mice. Colitis severity was independent of FFAR2 and FFAR3 signaling, FFAR2/3 KO mice were comparable to WT littermates in all parameters.

Conclusion

A low intake of dietary fiber reduced the colonic SCFA and reduced the resilience to colitis. Luminal SCFA were able to increase GLP-1 secretion in the isolated perfused colon and GLP-1 receptor signaling showed importance in the maintenance of BW in the diseased mouse. However, the pathway from a low fiber diet to severe colitis seemed to be independent of FFAR2/3 signaling.

References

A low intake of dietary fiber reduced the colonic SCFA and reduced the resilience to colitis. Luminal SCFA were able to increase GLP-1 secretion in the isolated perfused colon and GLP-1 receptor signaling showed importance in the maintenance of BW in the diseased mouse. However, the pathway from a low fiber diet to severe colitis seemed to be independent of FFAR2/3 signaling.

Disclosure

MY is affiliated with AbbVie A/S, however this work was performed prior to his employment and is not related to AbbVie A/S. MY is still affiliated with UCPH

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

Disease-specific knowledge plays a central role in chronic disease management. In patients with inflammatory bowel disease (IBD), limited knowledge is linked to poorer perceived health and increased discomfort (1).

Aims & Methods

This study assessed disease-specific knowledge among adult patients with IBD at a tertiary center and defined existing knowledge gaps. Factors associated with higher or lower levels of knowledge were explored.
The retrospective cohort study included 392 IBD patients who completed a comprehensive questionnaire between March 2020 and April 2021 (2). Questionnaire responses were analyzed alongside clinical records to quantify disease-specific knowledge. A scoring system was developed to quantify disease-specific knowledge (0–8 points), based on correct diagnosis, Montreal classification, complications, and current therapies. Scores were categorized as low (0–5) or high (6–8) knowledge levels. Associations between knowledge levels and disease-related, sociodemographic, and psychosocial factors were analyzed using logistic regression analysis.

Results

While most patients correctly identified their diagnosis (kappa: 0.863, CI: 0.816–0.905, p < 0.001) and advanced treatment (e.g. infliximab: kappa: 0.959, CI: 0.925–0.983, p < 0.001), knowledge gaps were observed regarding disease location (e.g. isolated proctitis in ulcerative colitis: kappa: 0.101, CI: –0.051–0.341, p = 0.128), complications, comorbidities, and certain other medications. In the univariate analysis a higher knowledge level was found in patients with Crohn’s disease, younger age at diagnosis, in patients with no disease activity, and treatment with biologics, in those receiving disability pension and in patients with a high Perceived Stress Questionnaire (PSQ) score for worries (table). A younger age at diagnosis (p = 0.028) and having Crohn’s disease (p < 0.001) were independently associated with higher knowledge levels whereas active disease was associated with lower disease-specific knowledge.
Table:
Univariate logistic regression analysis for items significantly associated with higher knowledge levels

Conclusion

Significant disease-specific knowledge gaps were identified, particularly concerning disease location, complications, and comorbidities. Targeted patient education should focus on addressing these specific deficits in susceptible groups.

References

1. Tormey LK, Reich J, Chen YS, Singh A, Lipkin-Moore Z, Yu A, et al. Limited Health Literacy Is Associated With Worse Patient-Reported Outcomes in Inflammatory Bowel Disease. Inflamm Bowel Dis. 2019;25:204–12.
2. Koletzko L, Klucker E, Le Thi TG, Breiteneicher S, Rubio-Acero R, Neuhaus L, et al. Following Pediatric and Adult IBD Patients through the COVID-19 Pandemic: Changes in Psychosocial Burden and Perception of Infection Risk and Harm over Time. J Clin Med. 2021;10:4124.

Introduction

Qualitative exit interviews provide key insights into patient experience and treatment expectations, which are particularly important in celiac disease (CeD) for which there are no current medications. Data relating to patients’ experiences are critical to understand what is considered a ‘meaningful change’ to patients when they participate in clinical trials. The objective of this study was to understand the clinical trial participants’ experience of CeD, their treatment expectations, and how they define meaningful changes in their symptoms as they exited from a phase 2 clinical trial.

Aims & Methods

Semi-structured telephone interviews of 60 minutes were conducted with eligible patients following a phase 2 double-blind, randomized, placebo-controlled trial in patients with moderate-to-severe CeD who maintained a gluten-free diet (GFD) for ≥ 12 months (NCT05353985).¹ Patients could provide more than one response to some questions. Interviews were blinded to treatment assignment and were audio recorded, transcribed and coded guided by an a priori coding dictionary and a qualitative analysis plan. Transcript analysis was facilitated by ATLAS.ti 9 software. This study was approved by the relevant Institutional Review Boards as part of the phase 2 trial.

Results

Overall, 29 English-speaking patients from 15 clinical sites in the USA were interviewed. Three patients exited the trial early. Most participants were female (23/29, 79.3%), the mean age was 50.6 years, and the mean duration of disease before study enrollment was 6.9 years. These characteristics were similar to the full clinical trial population in which most patients were female (115/153, 75.2%), the mean age was 46 years, and the average time to CeD diagnosis was 9 years. The most commonly reported symptoms were abdominal pain (27/29, 93.1%), bloating (26/29, 89.7%), and diarrhea (24/29, 82.8%). The most bothersome symptom reported was diarrhea (12/29, 41.4%).
Participants most often stated that they were hoping for an improvement in their CeD (25/29, 86.2%) providing descriptions that included the desire to be able to eat without the worry of potential gluten contamination.
Participants were asked if a ‘symptom-free day’ (SFD) (defined as a day with no diarrhea, abdominal pain, bloating, or nausea) would be meaningful. All participants agreed that the concept of SFD is important, with the majority stating that an increase of 1–2 SFDs per week would be meaningful (20/28, 71.4%).
Participants were also asked what improvements on the PGIS (Patient Global Impression of Severity) and PGIC (Patient Global Impression of Change) scales would be meaningful to them (participants could provide multiple responses). The majority (31 responses) reported that a 2-point decrease in severity would represent a meaningful improvement, followed by 21 responses for a 1-point decrease in PGIS. Regarding PGIC, most patients (15/25, 60.0%) stated that ‘much improved’ would indicate a meaningful change, followed by ‘a little improved’ (6/25, 24.0%).

Conclusion

Despite adhering to a GFD, patients experienced frequent and bothersome symptoms, particularly abdominal pain, bloating, and diarrhea, prior to enrolling in the study. This study identified potential thresholds for meaningful improvement in weekly SFDs and PGIS and PGIC scales. These data are important to inform the design and interpretation of future CeD clinical trials.

References

1. ClinicalTrials.gov. Available from: https://clinicaltrials.gov/study/NCT05353985 (Accessed April 1, 2025).

Disclosure

SG, MA, and DAL are employees of Takeda Development Center Americas, Inc. and receive stock or stock options. NH and SM are employees of RTI Health Solutions which received funding from Takeda for participation in this study.

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

Detection of autoantibodies directed to tissue transglutaminase (tTG) and deamidated gliadin peptide (DGP) is important in the assessment of individuals under clinical suspicion of celiac disease (CD).

Aims & Methods

In this study, we compared the analytical performance for the detection of autoantibodies to tTG (IgA isotype), of the MosaiQ AiPlex^® CD microarray (AiPlex CD. AliveDx, Switzerland), a CE-marked, novel, single-use, fully automated, multiplexed microarray immunoassay and routine methods. De-identified serum samples, characterized as reactive or non-reactive for tTG IgA as per the routine practice method of the evaluation site (EliA™ Celikey^® IgA, Phadia AB, Sweden), were tested with the evaluated device. Although AiPlex CD features the semi-quantitative measurement of both tTG IgA and IgG and anti-deamidated gliadin peptide (DGP) IgA and IgG antibodies, and qualitative measurement of total IgA in serum; this comparison was limited to tTG IgA as no samples characterized for other CD autoantibodies were available. Positive percent agreement (PPA) and negative percent agreement (NPA) were calculated. Double-sided 95% Confidence Intervals (CI) were calculated using Clopper-Pearson Exact Method.

Results

77 samples characterized as reactive for tTG IgA by the routine method and 90 samples characterized as non-reactive for this marker were included in the analysis. The evaluated device identified 73 out of 77 samples characterized as reactive by the routine method, for a PPA of 95% (95% CI: 87.2, 98.5). Out of the four discordant samples, one also yielded a non-reactive result for tTG IgG and reactive results for both DGP IgA and IgG in the evaluated device and negative anti-endomysial antibodies (EMA) by immunofluorescence; two samples were reactive to DGP IgA or DGP IgG by the evaluated device and one sample was non-reactive to all four markers and was negative to EMA. Regarding the samples characterized as non-reactive by the routine method, the evaluated device identified 86 out of 90, for an NPA of 96% (95% CI: 89.0, 98.7). For the four samples with discordant results, the evaluated device also yielded reactive results for at least one additional CD antibody (tTG IgG, DGP IgA, DGP IgG).

Conclusion

In this study, the evaluated microarray immunoassay showed high concordance with the compared routine method for the serological assessment of tTG IgA, a key marker in the evaluation of CD.

Disclosure

This study was funded by AliveDx Suisse SA, Eysins, Switzerland. Gerber Gomez and Christian Fischer are AliveDx employees.