Introduction

Chronic hepatitis, primarily caused by HBV, HCV, or HDV infections, remains a silent yet progressive condition leading to advanced hepatic fibrosis and cirrhosis. Non-invasive assessment tools, such as the FIB-4 score, play a crucial role in early-stage risk stratification. Emerging evidence suggests a potential interaction between gut microbiota alterations-particularly Small Intestinal Bacterial Overgrowth (SIBO)-and liver function, mediated through the gut-liver axis.

Aims & Methods

Aim: To evaluate the association between SIBO status and FIB-4 scores among patients with chronic hepatitis, and to assess whether SIBO positivity serves as an independent marker of hepatic fibrosis severity.
Methods: We retrospectively analyzed clinical and biochemical data from 122 patients with confirmed viral hepatitis. Parameters included age, gender, liver enzyme levels (ALT, AST, ALP, GGT), SIBO breath test results, and viral titers. FIB-4 scores were calculated using standard formulas. Patients were grouped based on SIBO status (positive vs. negative). Boxplot analysis and correlation metrics were used to visualize and quantify associations.

Results

Patients with SIBO positivity exhibited significantly higher median FIB-4 scores (1.87) compared to those who were SIBO-negative (1.23), (p < 0.05). The boxplot analysis underscored a wider interquartile range and rightward skew in SIBO-positive individuals. A moderate positive correlation (Spearman's rho = 0.41) was observed between viral titers and FIB-4 levels, indicating a synergistic impact of microbial overgrowth and viral load on liver fibrosis progression.

Conclusion

SIBO positivity appears to correlate with elevated FIB-4 scores in chronic hepatitis patients, suggesting microbial dysbiosis as a potential contributor to fibrotic burden. Incorporating gut health assessment into routine liver disease screening may enhance early detection of high-risk individuals. Further prospective studies are recommended to explore causality and therapeutic modulation of the gut-liver axis.

Introduction

Metabolic Associated Steatotic Liver Disease (MASLD) is a common metabolic disorder frequently accompanied by small intestinal bacterial overgrowth (SIBO). SIBO exacerbates MASLD progression through systemic inflammation, impaired intestinal barrier function, and metabolic disturbances. Rifaximin, an antibiotic with minimal systemic absorption, has proven effective in treating SIBO by improving microbiota composition and reducing inflammatory processes.

Aims & Methods

Aim was to evaluate the prevalence of SIBO among MASLD patients, assess the effects of rifaximin on gastrointestinal symptoms, biochemical markers, and lipid profiles, and explore its role in MASLD management.
Methods: The study included 152 patients with MASLD and 47 controls. SIBO was diagnosed using hydrogen breath testing. MASLD patients received rifaximin 200 mg three times daily for 14 days. Clinical symptoms, liver enzymes, inflammatory markers, and lipid profiles were assessed before and after therapy.

Results

SIBO was detected in 50% of MASLD patients compared to 23.4% of controls (p<0.05). Post-treatment, SIBO prevalence decreased to 32.4% (p<0.05). Significant improvements were observed in abdominal pain (reduced from 68 to 22 patients), bloating (from 75 to 19), and flatulence (from 71 to 38) (p<0.05). Biochemical parameters (ALT, AST, hs-CRP) and lipid profiles (decreases in total cholesterol and triglycerides, increase in HDL-C) significantly improved after rifaximin therapy.

Conclusion

Rifaximin effectively reduces SIBO prevalence and improves gastrointestinal symptoms, liver function, and metabolic parameters in MASLD patients. It may represent a valuable component of comprehensive MASLD management.

Introduction

Avoidant Restrictive Food Intake Disorder (ARFID) is increasingly recognized within the paediatric population and specialist clinics. However, there is sparse data on the prevalence and burden of ARFID within the adult general population. We addressed this issue.

Aims & Methods

A population-based Internet survey with pre-defined demographic quotas was conducted across the UK and USA in 2023. The survey collected data on demographics, body mass index (BMI), ARFID (using the nine-item ARFID screening tool, NIAS), disorders of gut-brain interaction (using the Rome IV diagnostic questionnaire), PHQ-15 somatic symptoms, PHQ-4 anxiety and depression, PROMIS-10 quality of life, and healthcare utilisation.

Results

In total, 4002 adults (mean age 47 [range 18-91] years and 50% females) completed the survey. Overall, 26.0% (n=1035) screened positive for ARFID, with similar results between the UK (23.0%) and USA (29.0%). The prevalence of positive ARFID screens by NIAS subscale were 15.3% for poor appetite, 13.9% for picky eating, and 6.2% for fear of aversive consequences. In all, 18.2% had a single ARFID domain, 5.7% had two domains and 1.9% had all three domains.
ARFID was more common in females than males (29.6% vs. 22.1%, OR 1.5), and highest amongst people aged 18-39 years (31.6%), followed by those aged 40-64 years (25.0%), and lowest in those 65 years and over (16.1%); p<0.001.
Individuals with ARFID - compared to those without ARFID - had a significantly higher prevalence of disorders of gut-brain interaction (51% vs. 37.5%, OR 2.2), including irritable bowel syndrome (11.8% vs. 4.0%, OR 3.2) and functional dyspepsia (25.8% vs. 7.0%, OR 4.6). They were significantly more likely to be underweight (BMI<18.5; 7.0% vs. 1.5%), experience greater somatic symptoms and mood disturbances, reduced mental and physical quality of life, and increased healthcare utilization (i.e. medication use and doctor visits). An increase in the number of ARFID domains was associated with greater general health impairment; p<0.001.

Conclusion

Elevated ARFID symptoms are common within the adult general population, affecting 1-in-4 people, and associated with substantial health burden. Increased awareness of ARFID will aid clinical service provision and future research on how to best manage this patient group.

Disclosure

Nil

Introduction

Confocal laser endomicroscopy (CLE) can detect acute duodenal epithelial disruption in response to food application, potentially identifying personalized elimination diets (1). A pilot study in functional dyspepsia (FD) showed that the 6-food elimination diet (6FED) provided symptom relief. (2). Earlier research in FD, however, showed that the high rate of acute food-induced mucosal alterations on CLE were not associated with altered permeability or changes in mast cell activation ex vivo (3).

Aims & Methods

To evaluate a personalized elimination diet in patients living with FD based on results of CLE, assessing duodenal mucosal changes to locally applied food solutions from the 6FED.
A randomized, double-blind, cross-over, sham-controlled trial was conducted in 17 Rome IV FD patients, in whom immunoglobulin E (IgE) sensitization to nutrients was excluded via food-specific serum IgEs. Baseline symptoms were assessed using the Leuven Postprandial Distress Scale (LPDS) and Patient Assessment of GI Disorders–Symptom Severity Index (PAGI-SYM). Index upper GI endoscopy (EGD) was followed at least 2 weeks later by an EGD with CLE. During CLE, duodenal mucosa was visualized at baseline and after consecutive, random administration of egg white, soy, milk, wheat, lyophilized fish/shellfish and nuts solutions. In case of a reaction to the first 2 food solutions, an additional CLE was scheduled. All patients underwent a crossover dietary intervention excluding foods to which they tested positively (real diet, RD) and negatively (sham diet, SD) in random order. Following 4 weeks of diet, LPDS and PAGI-SYM scores were reevaluated. Missing data were considered non-responder, based on an extreme case approach. Data are reported as mean ± SEM. Comparisons were done using a paired t-test or related-Samples Wilcoxon test, as applicable. Response rate was evaluated using a McNemar test. P<.05 is considered significant.

Results

Dietary outcome was available from 17 patients (age 35±3.7y, 16 female, BMI 22±0.7 kg/m2). In 7% of exams (n=2), acute alterations were already present at baseline. Twelve patients (71%) underwent a second CLE procedure. One patient dropped out after the first diet (which was RD). Three patients did not have a reliable RD/SD comparison due to non-response (n=1) or early response on CLE (n=2), underwent a standardized control diet, and were excluded from the analysis. Among the 14 patients in the cross-over dietary intervention, the proportion with a clinically significant 0.7 decrease in LPDS was similar for both diets (RD 4/14 vs. SD 2/14, p=0.41). No significant differences were found in LPDS subdomains or in the total PAGI-SYM score or PAGI-SYM fullness domain between the two diets (all p>.05).

Conclusion

In patients with FD, without systemic IgE-sensitization, CLE visualized a high rate of acute, food-induced, mucosal alterations, which could not be translated in symptom benefit following a dietary intervention excluding these foods vs. foods that did not trigger a reaction in this double-blind, controlled diet intervention study. None of the analyzed clinical outcome measures differed between the two diets. Given the results of this first double-blind controlled diet intervention in patients living with FD, CLE-based diets cannot be recommended in this population.

References

1. Fritscher-Ravens A, Schuppan D, Ellrichmann M, Schoch S, Rocken C, Brasch J, et al. Confocal endomicroscopy shows food-associated changes in the intestinal mucosa of patients with irritable bowel syndrome. Gastroenterology. 2014;147(5):1012-20 e4.
2. Schol J, Vanuytsel T, Routhiaux K, Huang I, Balsiger L, Van Den Houte K, et al. The six-food elimination diet improves symptoms of functional dyspepsia. Submitted for publication. 2025.
3. Van de Bruaene C, Schol J, Balsiger L, Raymenants K, Toth J, Farre R, et al., editors. Observation of local, food-induced changes of the duodenal mucosa in functional dyspepsia cannot be translated in permeability alterations or changes in mast cell activation ex vivo. F; 2024; Bangkok, Thailand: Neurogastroenterology And Motility.

Introduction

Small intestinal bacterial overgrowth (SIBO) is characterized by the presence of excessive gram-negative aerobic and anaerobic colonic bacteria in the small intestine^1,2, leading to increased carbohydrate fermentation and gas production. Symptomatology frequently overlaps with other gastrointestinal disorders³. This study aimed to identify factors associated with test positivity and improve patient selection for diagnostic evaluation.

Aims & Methods

Retrospective, unicentric study. A cohort of 34 patients underwent glucose hydrogen and methane breath testing for SIBO. Demographic, clinical, laboratory data and test results were analyzed.

Results

The cohort included 21 females (61.8%) and 13 males (38.2%), with a mean age of 46.5 ± 15.9 years. Chronic diarrhea was the leading indication for testing (82.4%), followed by abdominal pain (8.8%). Tests results were positive in 4 cases (11.8%). Positive patients had a higher mean age (56.0 ± 10.8 vs. 46.1 ± 15.8 years, p = 0.236) and a comparable gender distribution. Among positive patients, diarrhea was reported in 100% of cases, followed by abdominal distension (75%) and abdominal pain (50%). Folic acid levels were higher in the positive group (11.65 vs. 6.54 ng/mL, p = 0.074), while fecal calprotectin levels were significantly elevated (480 vs. 44.26 µg/g, p = 0.027). Altered small intestine anatomy due to prior surgical interventions was strongly associated with test positivity (p = 0.012), while systemic disorders affecting gastrointestinal motility showed a non-significant trend (p=0.136). Proton pump inhibitor use was not associated with test positivity (p = 1.0). Rifaximin treatment led to symptom improvement in all positive cases, but with no significant difference compared to negative patients (p = 0.444).

Conclusion

Elevated serum folate and fecal calprotectin levels may serve as indicators of underlying SIBO in the appropriate setting. Altered small intestine anatomy was strongly associated with test positivity, and could indicate SIBO under adequate intestinal transit time. These findings highlight the need for larger studies to refine patient selection and improve diagnostic strategies.

References

1. UpToDate. Small intestinal bacterial overgrowth: Etiology and pathogenesis. Available at: https://www.uptodate.com/contents/small-intestinal-bacterial-overgrowth-etiology-and-pathogenesis. Accessed January 19, 2025.
2. Pimentel M, Saad RJ, Long MD, Rao SSC. ACG Clinical Guideline: Small Intestinal Bacterial Overgrowth. Am J Gastroenterol. 2020;115(2):165-178. doi:10.14309/ajg.0000000000000501.
3. Sachdev AH, Pimentel M. Antibiotics for irritable bowel syndrome: Rationale and current evidence. Curr Gastroenterol Rep. 2012;14:439–45.

Introduction

Functional dyspepsia (FD) is a chronic gastrointestinal disorder characterised by meal-related symptoms, which a subset of patients attribute to the consumption of gluten-containing foods [1]. Recent evidence suggests that subtle duodenal immune activation is a feature of FD, as evidenced by elevated eosinophils [2] and impaired epithelial barrier function [3]. FD patients also exhibit an altered duodenal mucosa-associated microbiota (d-MAM) when compared to controls [4]. Given the microbiome’s involvement in the digestion of gluten, we hypothesised that the d-MAM determines the capacity for gluten to disrupt the epithelium and drive immune responses in FD patients.

Aims & Methods

Duodenal biopsies were collected from 10 FD patients and 7 asymptomatic controls. The d-MAM was cultured from biopsies in a habitat simulating media [5] containing 1% wheat-gluten, for up to 48hrs. Microbial cell pellets were frozen for future microbiome sequencing and the cell-free supernatants, containing d-MAM-digested gluten, were collected. Caco2 cells were challenged with the d-MAM-digested gluten, in a Transwell model of the intestinal epithelium (n=3, 2 technical replicates). Transepithelial electrical resistance (TEER) and protein expression of markers of epithelial integrity were measured in Caco2 cells and compared between treatments. Peripheral blood mononuclear cells (PBMCs) from FD patients (n=20) and controls (n=20) were stimulated with pooled samples of FD or control d-MAM-digested gluten, or left untreated, for 44 hours. For comparison to host enzymatic breakdown of gluten, matched PBMCs were also treated with α-chymotrypsin digested, deaminated gluten (CT gluten). The T cell phenotype and presence of activation-induced markers was assessed in PBMCs by flow cytometry.

Results

Challenge of Caco2 cells with gluten digested by the FD d-MAM resulted in a significant increase in Zonula occludens-1 (p=0.007), and reduction in Myd88 (p=0.03), compared to Caco2 cells challenged with control d-MAM-digested gluten. However, TEER readings were not altered between treatment groups in Caco2 experiments. In PBMC experiments, in response to stimulation with FD or control d-MAM-digested gluten, both FD and control PBMCs exhibited heightened expression of activation markers (CD4⁺OX40⁺CD25⁺), when compared to their respective unstimulated cells (p<0.05). When assessing the T-cell phenotype we observed that FD d-MAM-digested gluten promoted an increase in T-helper (Th) 2 cells in both FD (p=0.007) and control (p=0.0001) PBMCs. Meanwhile, control d-MAM-digested gluten stimulation resulted in elevated Th17.1 cells in FD (p<0.0001) and control (p=0.02) PBMCs, when compared to unstimulated cells. Alternatively, CT gluten stimulation did not alter any of the assessed lymphocyte populations in FD or control PBMCs when compared to unstimulated cells, suggesting host digestion of gluten isn’t sufficient to induce immune responses in FD.

Conclusion

Our findings suggest that the d-MAM of FD patients digest gluten in a way that promotes epithelial barrier remodelling and altered immune responses compared to the d-MAM from asymptomatic individuals. The promotion of a Th2 T-cell phenotype by the FD d-MAM is consistent with reports of increased Th2-associated cells, such as eosinophils, in FD patients [6]. These results highlight the likely role of microbiome-gluten interactions in FD, indicating the potential for novel dietary therapies and microbial approaches to management.

References

1. Potter, M., et al., Incidence and prevalence of self-reported non-coeliac wheat sensitivity and gluten avoidance in Australia. Med J Aust, 2020. 212(3): p. 126-131.
2. Shah, A., et al., Duodenal Eosinophils and Mast Cells in Functional Dyspepsia: A Systematic Review and Meta-Analysis of Case-Control Studies. Clinical Gastroenterology and Hepatology, 2022. 20(10): p. 2229-2242.e29.
3. Puthanmadhom Narayanan, S., et al., Duodenal Mucosal Barrier in Functional Dyspepsia. Clin Gastroenterol Hepatol, 2022. 20(5): p. 1019-1028.e3.
4. Shanahan, E.R., et al., Alterations to the duodenal microbiota are linked to gastric emptying and symptoms in functional dyspepsia. Gut, 2023. 72(5): p. 929-938.
5. Schooth, L., Defining the Role of the Mucosa-Associated Microbiota in Digestive Health and Disease Using Novel ex-vivo Combinations of Microbe Culture with Metagenomics. 2024 [Doctoral thesis, The University of Queensland], UQ eSpace.
6. Burns, G.L., et al., Type 2 and type 17 effector cells are increased in the duodenal mucosa but not peripheral blood of patients with functional dyspepsia. Front Immunol, 2022. 13: p. 1051632.

Disclosure

JP, EH, CN, SS, SR, MS, KH, GB, and KD have no disclosures to report.
NT: Financial support from: BluMaiden (microbiome advisory board) (2021), Comvita Mānuka Honey (2021) (digestive health), Biocodex (functional dyspepsia tool), Microba (microbiome advisory board) outside the submitted work. In addition, Dr. Talley has a patent Nepean Dyspepsia Index (NDI) 1998, Biomarkers of IBS licensed, a patent Licensing Questionnaires Talley Bowel Disease Questionnaire licensed to Mayo/Talley, a patent issued, “Diagnostic marker for functional gastrointestinal disorders” Australian Patent Application WO2022256861A1via the University of Newcastle and UniQuest (University of Queensland) and ”Methods and compositions for treating age-related neurodegenerative disease associated with dysbiosis” US Application No. 63/537,725. Dr. Talley is supported by funding from the National Health and Medical Research Council (NHMRC) to the Centre for Research Excellence in Digestive Health and he holds an NHMRC Investigator grant.
SK: Grants from National Health and Medical Research Council (Ideas Grant and Centre for Research Excellence), grants from Viscera Labs (Research contract), grants from Microba Life Science (Research contract), personal fees from Gossamer Bio, personal fees from Anatara Lifescience, personal fees from Immuron, personal fees from Microba Life Science.

Introduction

Eosynophilic oesophagitis (EoE) is a chronic disease which clinically presents with symptoms related to oesophageal dysfunction while pathologically it is characterized by eosinophilic infiltration of oesophageal epithelium. Most patients with EoE present food and/or inhalant allergies symptoms. The results of animal models studies and genetic studies, as well as efficacy of elimination diets in managing the symptoms, suggest an atopic background of the disease.

Aims & Methods

The aim of this study was to evaluate the prevalence of EoE in a group of patients with upper gastrointestinal symptoms and food and/or inhalant allergies and to assess the influence of drugs used in type I allergies on the results of endoscopic, histopathological and immunohistochemical tests.
Methods. This was a prospective observational study. Patients with inhalant/food allergies and upper esophageal symptoms formed study group while control group formed patients without allergy diagnosed with dyspepsia or irritbale bowel syndrome. All study participants were tested for allergies including prick testing, blood tests, all participants were evaluated with a gastroscopy with specimen collection. Oesophageal specimens were stained for eotaxin-1 and desmoglein-1.

Results

Based on histopathology results eosinophilic oesophagitis was found in 9 of the 73 patients from the study group. All patients with EoE presented with multimorbidity and were diagnosed with at least one allergic disease in addition to EoE. Positive staining for CCL-11 was found in 56 (78%) patients in the study group, including all patients with EoE while ony in 3 (17%) individuals from control group. The presence of DSG-1 in oesophageal specimens was detected in 6 (7%) subjects from the study group in contrary to 14 (78%) subjects from the control group. DSG-1 was not found in any of the specimens of patients diagnosed with EoE.

Conclusion

EoE is rare disease usually accompanied by allergic multimorbidity. Positive staining for eotaxin-1 and negative staining for desmoglein-1 in patients with esophageal symptoms and allergy but who did not met EoE diagnostic criteria, could be indicative of subclinical course of the disease or masking effect of corticosteroids. It is now critically important for both researchers and practicing clinicians to recognize that eosinophilic esophagitis (EoE) is not a homogeneous disease but rather consists of multiple subtypes (phenotypes). The so-called "classic" form of EoE—defined by current diagnostic criteria as having more than 15 eosinophils per high-power field on histopathological examination—appears to represent only the tip of the iceberg. There is an urgent need for further research to refine endoscopic techniques, expand the scope of histopathological assessments, and identify novel biomarkers to better define the distinct phenotypes of eosinophilic esophagitis.

References

1. Hirano, I.; Chan, E.; Rank, M.; Saraf, RN.; Stollman, NH.; Stukus, DR.; et al. AGA institute and the joint task force on allergy-immunology practice parameters clinical guidelines for the management of eosinophilic esophagitis. Ann Allergy Asthma Immunol 2020; 124: 416-23
   
2. Greuter, T.; Straumann, A.; Fernandez-Marrero, Y.; Germic, N.; Hosseini, A.; Yousefi, S.; et al. Characterization of
   eosinophilic esophagitis variants by clinical, histological, and molecular analyses: A cross-sectional multi-center study.
   Allergy. 2022;77(8):2520-2533. doi: 10.1111/all.15233.