Introduction

Patients with Disorders of Gut-Brain Interaction (DGBI) often experience meal-related symptoms, potentially due to carbohydrate intolerances like fructose and/or lactose. While breath tests are common for exploring carbohydrate malabsorption, assessing intolerances, defined by the onset of gastrointestinal (GI) symptoms after a defined load of carbohydrates, is valuable. The adult carbohydrate perception questionnaire (aCPQ) can be used for detecting carbohydrate intolerances (1).

Aims & Methods

We aimed to determine lactose and fructose intolerance prevalence in DGBI and characterize these patients. DGBI patients who underwent fructose (25g) and lactose (25g) breath tests alongside the aCPQ in our tertiary center between May 2022 and December 2023 were included. Carbohydrate intolerance was a 20 mm increase in any of the five Visual Analog Scales (VAS) scores (for abdominal pain, nausea, diarrhea, bloating, and flatulence) in aCPQ. An increase from baseline of ≥20 ppm in exhaled H2 or ≥10 ppm of CH4 (≥20 ppm for fructose) indicated malabsorption. Patients completed questionnaires on irritable bowel syndrome (IBS) symptom severity (IBS-SSS), somatic symptoms (PHQ-15), quality of life (QOL)(GIQLI), anxiety, and depression (HAD).

Results

We included 314 DGBI patients, among them, 124 were lactose intolerant, 138 were fructose intolerant, and 77 were intolerant to both carbohydrates. Lactose intolerant patients were younger (42± 15.9 vs 46 ± 15.3; p=0.022), and more likely to have lactose malabsorption and fructose intolerance, while fructose intolerant patients were more likely to have fructose malabsorption, lactose intolerance, and higher anxiety/depression levels. Both intolerant groups were more likely to be female (81.5% vs 61.6%; p<0.0001 for lactose, 77.5% vs 63.1%; p=0.006 for fructose), with 2 DGBI or more (63.1% vs 40.7%; p<0.0001 for lactose, 57.4% vs 43.5%; p=0.021 for fructose), to have a reduced QOL, higher levels of GI symptoms, and somatic symptoms (table). Logistic regressions showed independent associations of female sex, fructose intolerance, and lactose malabsorption with the lactose intolerance variable, and IBS symptom severity, lactose intolerance, and fructose malabsorption with the fructose intolerance variable.

Table: Comparison of DGBI patients with and without lactose and fructose intolerance

Conclusion

DGBI patients with lactose and fructose intolerance exhibit severe IBS symptoms and reduced QOL. Interestingly, intolerance to one carbohydrate is associated with malabsorption of this specific carbohydrate and the coexistence of intolerance to the other carbohydrate.

References

1. Hammer, Johann et al. European journal of gastroenterology & hepatology 2021, doi:10.1097/MEG.0000000000001880

Disclosure

CM has served as a consultant/advisory board member for KyowaKirin, Norgine, Biocodex, Mayoly Spindler, Tillots, Ipsen, Nestlé HealthScience and Viatris.
FM has served as a consultant/speaker for Laborie, Medtronic, Dr Falk Pharma.
GG has served as a consultant/speaker for Laborie, Medtronic, Kyowa Kirin, Lilly and Enterra medical.

Introduction

Behaviours such as supra-gastric belching, gastric belching, and aerophagia, often identified during oesophageal physiology studies (e.g., 24-hour pH and impedance study), are known to exacerbate symptoms like reflux, bloating, and regurgitation. These behaviours are frequently misunderstood and may lead to unnecessary referrals to specialists or invasive interventions. Upper GI biofeedback (UGI BFB) therapy offers a tailored, non-invasive approach to help patients manage these behaviours. By teaching specific techniques such as diaphragmatic breathing, open-mouth posture, and the multiple rapid swallow technique, patients are empowered to take control of their symptoms, improve their quality of life, and reduce reliance on surgical or gastroenterology pathways.

Aims & Methods

• Participants: Between December 2022 and December 2024, 35 patients were referred for UGI BFB therapy. Most referrals (n=31) came after oesophageal physiology studies, with additional referrals from gastroenterologists for belching and bloating (n=2) and from clinical endoscopists for persistent hiccups and audible wheezing (n=2).
• Intervention: Patients attended a one-hour education session in the Gastrointestinal (GI) Physiology unit. This included a review of diagnostic findings and practical training in diaphragmatic breathing, open-mouth posture, and the multiple rapid swallow technique. A follow-up telephone consultation at 6–8 weeks allowed for monitoring progress. For cases of poor oesophageal clearance, referring clinicians were advised to consider prokinetics. For frequent gastric belching, small intestinal bacterial overgrowth (SIBO) breath testing was recommended to assess any additional contributing factors.

Results

• Supra-gastric belching episodes were reduced by 50% (mean: 24 episodes pre-therapy to 12 post-therapy; p<0.001).
• GERD-HRQL scores improved by 45%, indicating significant quality-of-life improvements (mean: 22 pre-therapy to 12 post-therapy; p<0.001).
• 75% of patients reported substantial reductions in belching, bloating, and reflux-like symptoms.
• Half of the patients (50%) no longer required specialist referrals, as symptoms were successfully managed with therapy or GP-led interventions, including prokinetics or medications for hypersensitivity.
• Stress emerged as a critical factor for most patients. Relaxation techniques, mindfulness, and stress management strategies played an important role in symptom control. One patient, who became a mental health first aider at work, reported long-term symptom relief due to stress reduction efforts.

Conclusion

Upper GI biofeedback therapy is a valuable approach for addressing behavioural contributors to symptoms like air swallowing, belching, and bloating. A multidisciplinary approach, involving cognitive behavioural therapy or hypnotherapy alongside UGI BFB, can be highly beneficial. The GI Physiology team also recognises its limitations and has found that referrals to Speech and Language Therapy can be instrumental when patients are unable to engage fully with the therapy. This collaborative, patient-centred approach ensures that UGI BFB therapy not only reduces the need for invasive procedures and specialist consultations but also empowers patients to adopt long-lasting lifestyle and behavioural changes.

Introduction

Colorectal cancer (CRC) screening is well established worldwide. However, the suboptimal sensitivity of the Fecal Immunochemical Test (FIT) for precancerous lesions justifies the search for new tools, namely microRNAs (miRs). In recent years, the detection of these molecules in liquid biopsies has gained increasing interest, as they reflect CRC progression and enable the early detection of precancerous lesions. Moreover, using miRs as a blood-based screening test could potentially increase patient adherence.

Aims & Methods

In this context, we aimed to identify circulating miR profiles for the early detection of CRC. Based on our previous literature review, we selected four miRs (miR-21-5p, miR-92a-3p, miR-451a and miR-199a-5p) with the best performance for the detection of CRC and high-grade dysplasia lesions (HGD). MiR expression was evaluated using RT-qPCR in plasma samples from 80 individuals who underwent colonoscopy with different clinical outcomes, namely, individuals without lesions found on colonoscopy, low-grade dysplasia lesions, high-grade dysplasia lesions, and patients diagnosed with CRC.

Results

Our findings demonstrate a decreased expression of all miRs in CRC and HGD lesions. Regarding HGD identification, miR-21-5p demonstrate a sensitivity of 68% (95% CI: 46 – 85%) and a specificity of 100% (95% CI: 84 – 100). Moreover, miR-92a-3p, miR-451a and miR-199a-5p demonstrated a sensitivity higher than 85% for HGD lesions detection, despite low sensitivity (around 70%). Concerning CRC detection, miR-92a-3p and miR-199a-5p demonstrated sensitivity of approximately 65%, with specificities of 70%, for miR-92a-3p (95% CI: 48 – 85%), and 80% for miR-199a-5p (95% CI: 58 – 92%). Furthermore, miR-21-5p showed outstanding performance in CRC identification with a sensitivity of 95% (95% CI: 75 – 100%), for an AUC of 0.900 (95% CI: 0.807 – 0.993). Moreover, when a negative result was obtained for one of these miRs, the presence of colorectal cancer lesions could be accurately excluded (negative predictive value: 98%).

Conclusion

These findings suggest that circulating miRs have the potential to improve the detection of precancerous lesions, surpassing the performance of FIT. Moreover, given their accuracy in identifying individuals without lesions, they could serve as effective confirmatory screening tools, reducing the number of unnecessary colonoscopies.
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Clinical Case Summary

Non celiac gluten wheat sensitivity (NCGWS) is a syndrome whose symptoms are strictly related to gluten ingestion and presents with both intestinal and extraintestinal manifestations. However a liver involvement has never been shown. We report one case of NCGWS presenting with altered bowel habits, a persistent raise of alanine aminotransferase (ALT), aspartate aminotransferase (AST) since childhood and migraines. Gamma GT, alcaline phosphatase, bilirubin, were all within the range of normality over multiple testing. Viral serology (HAV, HBV, HCV), markers for autoimmune hepatitis (ANA, anti-smooth muscle and liver kidney microsome), protein electrophoresis, iron metabolism markers, urinary and blood copper were normal. Abdominal ultrasound reported liver size within the range of normality, regular structure and without focal lesions. No gallstones nor biliary tract dilation. Hepatic elastography was normal. Patient denied alcohol consumption at the time. Coeliac screening was negative (total IgA, IgA tTg-2 and IgA anti-endomysium). She performed a gastroscopy which showed regular macroscopic features of both stomach and duodenum. The histology showed non-specific signs of inflammation (Marsh 0). We found a rise of native IgG anti gliadin (AGA) >100 U/ml and serum zonulin (47,4 ng/ml, ULN <38). Therefore, we proposed a possible diagnosis of NCGWS following Salerno criteria and a gluten free diet (GFD) was recommended to the patient. The adherence to a GFD normalised bowel habits, migraines and the levels of liver enzymes. The pathogenesis of the liver damage in NCGWS is unclear. We hypothesized that the gut barrier dysfunction led to a translocation of toxins and antigens to the liver, therefore creating damage and a mild raise of hepatic transaminase. To date, this case is the first reporting a relation between altered liver enzymes and NCGWS. Further evidence is needed to better establish the link between these two conditions.

References

Hollon J, Puppa EL, Greenwald B, Goldberg E, Guerrerio A, Fasano A. Effect of Gliadin on Permeability of Intestinal Biopsy Explants from Celiac Disease Patients and Patients with Non-Celiac Gluten Sensitivity. Nutrients. 2015 Mar;7(3):1565–76.
Tripathi A, Debelius J, Brenner DA, Karin M, Loomba R, Schnabl B, et al. The gut-liver axis and the intersection with the microbiome. Nat Rev Gastroenterol Hepatol. 2018 Jul;15(7):397–411.
​Garcia-Mazcorro JF, Rivera-Gutierrez X, Cobos-Quevedo ODJ, Grube-Pagola P, Meixueiro-Daza A, Hernandez-Flores K, et al. First Insights into the Gut Microbiota of Mexican Patients with Celiac Disease and Non-Celiac Gluten Sensitivity. Nutrients. 2018 Nov;10(11):1641.

Introduction

Gut transit time is a key modulator of host-microbiome interactions, influencing gut microbiota composition and fecal metabolites concentrations. Prolonged colonic transit time is associated with greater microbial diversity, increased proteolytic fermentation activity and reduced concentrations of short-chain fatty acids (SCFAs). Metabolites derived from protein fermentation (such as ammonia, indole, p-cresol, and hydrogen sulfide) can impair epithelial integrity, while SCFAs, produced from nondigestible carbohydrates, support mucosal health through anti-inflammatory and antineoplastic effects. An imbalance between these metabolites may compromise colonic homeostasis, predisposing colonocytes to aberrant proliferation and increasing the risk of neoplastic transformation. These early alterations can be clinically detected through the presence of adenomatous polyps during colonoscopy, marking a critical window for preventive strategies.

Aims & Methods

The aim was to evaluate the role of gut transit time in shaping gut microbiota composition and fecal levels of bacterial-derived metabolites in individuals with a history of colorectal polyps. Thirty-three individuals who had undergone a colonoscopy were recruited and categorized based on gut transit time, assessed using the blue dye method. Fecal samples were collected and cocentrations of SCFAs, ammonium and indole were quantified using gas chromatography, a fluorometric assay and a colorimetric assay, respectively. The V3–V4 region of the 16S rRNA gene was sequenced using the Illumina NovaSeq platform. Sequence variant inference, quality filtering, chimera removal, and paired-end read merging were performed using the DADA2 pipeline in R, followed by taxonomic assignment with the Silva reference database. Alpha diversity was assessed by measuring richness (number of operational taxonomic units) and diversity (Shannon index). Beta diversity was analyzed using Canonical Correspondence Analysis (CCA) based on Bray–Curtis distances, with group differences tested via PERMANOVA. Linear discriminant analysis with an LDA score threshold >2 was applied to identify differentially abundant taxa.

Results

Alpha-diversity did not differ between groups with different gut transit times. Regarding Beta diversity, CCA based on Bray–Curtis distance showed a non-significant trend (p=0.095), whereas PERMANOVA analysis revealed a statistically significant effect (p=0.038), indicating that gut transit time explains a significant portion of the variance in microbial composition. Individuals with slow transit time exhibited an enrichment of several bacterial families from the phyla Actinobacteria (Micrococcaceae, Actinomycetaceae, Eggerthellaceae) and Firmicutes (Christensenellaceae, Ruminococcaceae, Lachnospiraceae, Peptostreptococcaceae and Veillonellaceae). A trend toward lower fecal SCFAs concentrations was observed in slow transit group compared to individuals with normal transit (69.2 ± 43.2 vs. 98.6 ± 34 umol/gr, p=0.087). No significant differences in fecal ammonium or indole concentrations were detected between groups. Multinomial logistic regression analysis indicated that higher levels of SCFA were linked to a lower likelihood of being in the slow transit group (p = 0.055). No differences were found in the frequency of polyp diagnosis according to transit time classification (p=0.495).

Conclusion

This study confirms that gut transit time influences both microbiota composition and SCFA levels. These findings highlight the relevance of gut transit modulation as a preventive target in individuals at risk of colorectal neoplasia.

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

Functional diseases of the gastrointestinal tract are a common diagnosis, with the most common manifestations being functional dyspepsia and IBS. The pathophysiological mechanisms and etiology of this group of diseases are not fully understood, but stress is believed to play a key role.

Aims & Methods

This study aims to evaluate the effectiveness of a low-histamine diet in patients with irritable bowel syndrome. Patients who meet the ROME IV criteria were included in the study. The study included 120 patients, divided into three groups: low- histamine diet, FODMAP diet and mediterranian diet.Questionnaires were used to assess stress levels PSS-4, anxiety GAD-7, severity of IBS - IBS Severity Score, and quality of life. The questionnaires were completed three times: both at the beginning of the study, immediately after the end of the 4-week diet, and one month after the end of the diet therapy.

Results

The low-histamine diet led to a statistically significant improvement in IBS symptoms compared to baseline. These findings suggest that the dietary intervention had a positive therapeutic effect ( low- histamine diet : t = 9.6181, p-value < 0.001, low FODMAP diet Z = 22, p-value < 0.001, mediterannian diet Z =119, p-value < 0.001).

Conclusion

Dietary therapy plays a key role in the management of IBS. The low-histamine diet shows promising results and may serve as a viable alternative to the FODMAP diet.

Disclosure

The study was launched after receiving approval from the Research Ethics Committee (REC) at the Medical University "Prof. Dr. Paraskev Stoyanov" – Varna, protocol 111/ 20.01.2022y.Data were processed and analyzed using appropriate statistical methods chosen according to the nature of the variables and research questions. The analysis includes:

• Evaluation of the statistical significance of the main and interactions between the factors (Repeated Measures with Wicolxon and Paired t-test).
• Regression analysis to assess relationships between dependent and independent variables. As well as using heteroskedasticity-robust standard error estimates (HC3) to ensure accuracy of regression analysis results.