Introduction

Recent societal guidelines suggest there is no role for hydrogen and methane breath testing (HMBT) to exclude small intestinal bacterial overgrowth (SIBO) in patients with diarrhoea predominant irritable bowel syndrome (IBS) and to treat symptoms with rifaximin empirically^1,2. However, a positive result for SIBO with lactulose HMBT has been shown to predict more favourable outcomes to rifaximin in patients with diarrhoea predominant IBS³. We wanted to investigate if symptoms and medical history can predict lactulose HMBT outcome hence justifying treatment of SIBO without a formal diagnosis.

Aims & Methods

A large questionnaire-based study was conducted in over 1000 patients of which 731 completed lactulose HMBT. The 26-item questionnaire included questions about medical history, symptoms, and pattern of symptoms, and we used this to identify any positive predictors for SIBO on HMBT. A positive lactulose HMBT was determined by a rise of ≥20 ppm in breath hydrogen from baseline within 90 minutes³. Breath samples were analysed using gas chromatography. Associations and predictors were calculated using chi square tests and logistic regression, respectively.

Results

Bloating (93.6%), abdominal pain (87.3%), and diarrhoea (80.3%) were the most common symptoms reported by those with a positive result for SIBO, but their duration, frequency and onset were no different to patients with a negative result (P > 0.05). There were no positive predictors for SIBO on lactulose HMBT based on symptoms, medications or medical history except for chronic low ferritin (P = 0.025).

Conclusion

This large questionnaire study has demonstrated that symptoms and medical history cannot predict HMBT outcomes for SIBO. Therefore, treatment of SIBO without a diagnosis confirmed on HMBT may lead to unnecessary antibiotic use and costs.

References

1. Vasant DH, Paine PA, Black CJ, Houghton LA, Everitt HA, Corsetti M, Agrawal A, Aziz I, Farmer AD, Eugenicos MP, Moss-Morris R, Yiannakou Y, Ford AC. British Society of Gastroenterology guidelines on the management of irritable bowel syndrome. Gut. 2021 Jul;70(7):1214-1240.
2. Savarino E, Zingone F, Barberio B, Marasco G, Akyuz F, Akpinar H, Barboi O, Bodini G, Bor S, Chiarioni G, Cristian G, Corsetti M, Di Sabatino A, Dimitriu AM, Drug V, Dumitrascu DL, Ford AC, Hauser G, Nakov R, Patel N, Pohl D, Sfarti C, Serra J, Simrén M, Suciu A, Tack J, Toruner M, Walters J, Cremon C, Barbara G. Functional bowel disorders with diarrhoea: Clinical guidelines of the United European Gastroenterology and European Society for Neurogastroenterology and Motility. United European Gastroenterol J. 2022 Jul;10(6):556-584.
3. Rezaie A, Heimanson Z, McCallum R, Pimentel M. Lactulose Breath Testing as a Predictor of Response to Rifaximin in Patients With Irritable Bowel Syndrome With Diarrhea. Am J Gastroenterol. 2019 Dec;114(12):1886-1893.

Introduction

A considerable proportion of patients with disorders of gut-brain interaction suffer from carbohydrate intolerances. The European Guideline¹ recommends a diagnostic evaluation that combines malabsorption testing using hydrogen breath tests with symptom assessment using the validated aCPQ². This study evaluates 1) the relationship between the severity of abdominal symptoms (pain, nausea, bloating, flatulence, diarrhea) in patients' histories and the results of malabsorption and intolerance testing, and 2) the response to a diet in patients diagnosed with carbohydrate intolerance (positive aCPQ) with or without malabsorption (pos. or neg. breath test).

Aims & Methods

This is a retrospective analysis of 1,139 tests performed between February 2017 and June 2024in 708 patients (62% female; mean age 42 ± 16 years) referred for evaluation of suspected carbohydrate intolerance at the Medical Universities of Graz and Vienna. Malabsorption was evaluated by breath tests (H₂ maximum rise above baseline and area under the curve), and intolerance by the aCPQ after ingestion of 50 g lactose (n=588), 25 g fructose (n=550) or 25 g trehalose (n=1). Symptom intensities over the preceding six months for diarrhea, bloating, nausea, flatulence, and abdominal pain were assessed using the Bowel Disease Questionnaire (BDQ; VAS scale 0–100 mm). 63 patients with intolerance completed a 4- to 12-week diet. Symptoms after the diet were evaluated using identical VAS scales, with symptom intensity assessed within the previous 10 days. The difference between the VAS scores of each symptom (deltaVAS) before and after diet was determined.

Results

625 tests revealed intolerance (pos aCPQ), 373 malabsorption (pos. breath test), 273 tests a combination of intolerance and malabsorption and 414 tests were negative in both tests. In patients with intolerance weak positive correlations were found between each of the five symptoms in the preceding six months and maximum symptom intensity of the respective symptom on the aCPQ (r ranging from 0.17 to 0.31; p<0.001); the strongest correlation was observed for bloating and the weakest for diarrhea. This applied for the lactose and fructose groups. These correlations were present whether or not malabsorption was detected in the breath test. No significant correlation was observed between BDQ symptom severity and breath test results. The table shows symptom severity by VAS scoring before and after diet in patients with aCPQ-diagnosed intolerance: dietary intervention led to a significant improvement in all symptom severities (p>0.001). For all of the five symptoms strong correlations were observed between baseline symptom severity in the preceding 6 months (BDQ) and the extent of symptom improvement after the diet (delta VAS; *p<0.001). Malabsorption detected by breath test did not predict dietary response. Weak positive correlations were noted between aCPQ symptom severity and deltaVAS for nausea (r=0.32; p=0.012) and bloating (r=0.37; p=0.003).

Conclusion

Diagnosis of intolerance using the aCPQ identifies patients who benefit from dietary intervention. Patients who have the most severe baseline symptom history respond the best. Symptom history is a weak predictor of carbohydrate intolerance, and breath tests are not useful for explaining baseline symptom history or guiding treatment.

References

1. Hammer HF et al. European guideline on indications, performance and clinical impact of hydrogen and methane breath tests in adult and pediatric patients: EAGEN, ESNM and ESPGHAN consensus. United European Gastroenterol J. 2022;10:15-40 https://doi.org/10.1002/ueg2.12133
2. Hammer J et al. Carbohydrate induced gastrointestinal symptoms: development and validation of a test-specific symptom questionnaire for an adult population, the Adult Carbohydrate Perception Questionnaire aCPQ. Eur J Gastroenterol Hepatol 2021:32(2):171-177. doi: 10.1097/MEG.0000000000001880.

Clinical Case Summary

A 67-year-old man initially presented in 2020 with intermittent dysphagia for solid food. An endoscopy of the upper gastrointestinal tract revealed an inflammatory, presumed peptic stenosis at the level of the Z-line. No hiatus hernia was present. A balloon dilatation was performed and therapy with proton pump inhibitors was started. This maintained remission until 2023, when he represented with frequent bolus retention, retrosternal chest pain and regurgitation. A repeat endoscopy appeared normal; however, biopsies revealed lymphocytic esophagitis. A high-resolution oesophageal manometry was performed to clarify the cause of dysphagia. Water swallows showed no abnormal findings; however, the patient had repeated, symptomatic outlet-obstruction during the solid test meal. This finding is often seen in eosinophilic esophagitis.¹ The diagnosis of primary lymphocytic esophagitis, considered to be a variant of this condition,² was proposed. Treatment with oro-dispersible budesonide (1mg bid) was started.
At the same time, an abnormal AV conduction pattern was noted on ECG. Echocardiography and a cardiac stress test were normal; however, CT imaging showed bihilar lymphadenopathy with peri-lymphatic pulmonary nodules. Broncho-alveolar lavage showed lymphocytic alveolitis (29% lymphocytes) and an elevated CD4/CD8 ratio (ratio = 4). ACE (51 U/l) was normal and granulomas were not seen on fine needle aspiration of the lymph nodes; however, the diagnosis of stage 2 pulmonary sarcoidosis was confirmed on PET-CT. Oral prednisolone (30mg od) replaced locally active steroids. The patient was symptom free after one month treatment.
Sarcoidosis is a granulomatous disease that often affects the lungs, skin and lymph nodes; however, involvement of the digestive tract is rare, and secondary lymphocytic esophagitis has hardly ever been described.³ The investigation, primary or secondary aetiology, and management of dysphagia in this case of lymphocytic esophagitis will be discussed.

References

1. Sykes C, Fairlamb G, Fox M, et al. Assessment of Esophageal Motility in Patients With Eosinophilic Esophagitis: A Scoping Review. J Clin Gastroenterol 2023;57:10-30.
2. Greuter T, Straumann A, Fernandez-Marrero Y, et al. Characterization of eosinophilic esophagitis variants by clinical, histological, and molecular analyses: A cross-sectional multi-center study. Allergy 2022;77:2520-2533.
3. Brito-Zeron P, Bari K, Baughman RP, et al. Sarcoidosis Involving the Gastrointestinal Tract: Diagnostic and Therapeutic Management. Am J Gastroenterol 2019;114:1238-1247.

Disclosure

None of the authors have any conflict of interest to disclose

Introduction

The Mediterranean Diet (MedDiet) has proven to be highly beneficial to human health thanks to its balanced combination of anti-inflammatory and antioxidants nutrients. Several studies^1,2,3 have highlighted the inverse relationship between MedDiet, visceral adiposity, and chronic conditions, namely cardiovascular disease, diabetes, and cancer. The Chrono Med Diet Score (CMDS)⁴ is a recently validated, easy-to-use adherence questionnaire to the MedDiet that, differently from previously validated scores⁵, considers food, lifestyle habits and time of food consumption. Here, we evaluated the CMDS ability to predict the increased risk of gastrointestinal (GI) cancer (colorectal, liver, and stomach) development in a cohort of metabolic subjects.

Aims & Methods

We enrolled 261 patients who accessed our outpatients’ clinic to assess fatty liver disease and Metabolic Syndrome and followed them for a period of 3.2 years. At first evaluation, CMDS was calculated for each patient. Fatty Liver Index (FLI) was calculated as= (e 0.953 × loge (triglycerides) + 0.139 × BMI + 0.718 × loge (GGT) + 0.053 × WC − 15.745)/(1 + e 0.953 × loge (TG) + 0.139 × BMI + 0.718 × loge (GGT) + 0.053 × WC − 15.745) × 100. ROC curves were used to identify the capability of each score to predict cancer development. T-test comparisons for CMDS values were performed for cancer (prostate, bladder, ovarian, and endometrium) and GI cancer diagnosis. P-values lower than 0.05 were considered significant. Chi-square test was used to calculate the associated Odds Ratio (OR) with 95% confidence interval (CI).

Results

A total of 47 out of 261 patients developed cancer. CMDS showed a significant discriminative power (AUC 0.7428) to predict cancer development with a cut-off of 11 (77% sensitivity, 70% specificity, p-value <0.001), while in the 26 subjects with a diagnosis of GI cancer (AUC 0.7961) the cut-off was 13 (67% sensitivity, 85% specificity). Among subjects with CMDS ≤13, those who developed GI cancer showed significantly altered metabolic markers, namely waist circumference, triglycerides, fasting glucose, HDL cholesterol, and FLI compared to patients who did not develop cancer during the follow-up period (see Table). Values of CMDS ≤13 significantly increased the risk of GI cancer with an OR of 3.41 (95% CI: 1.99-6.12). Intriguingly, CMDS was significantly lower (7.1±0.4) in subjects who were diagnosed with gastrointestinal cancer, compared to patients that developed non – gastrointestinal cancer (9.5±0.7).

Conclusion

In our cohort, adherence to the MedDiet is strongly associated to an increased risk of cancer development in metabolic subjects. This association is even stronger in patients who developed GI cancer, as demonstrated by the significant correlation between the CMDS and specific parameters of dysmetabolism, such as visceral adiposity, dyslipidemia, and liver fibrosis. Taken together, our data indicates not only that the risk of GI cancer can be identified using the CMDS as a non-invasive reference method, but also emphasize that dietary and lifestyle changes, promoting a higher adherence to the MedDiet, are significantly recommended for people affected by dysmetabolic conditions.

References

1. Bamia, C.; Lagiou, P.; Buckland, G.; Grioni, S.; Agnoli, C.; Taylor, A.J.; Dahm, C.C.; Overvad, K.; Olsen, A.; Tjønneland, A., et al. Mediterranean diet and colorectal cancer risk: results from a European cohort. European Journal of Epidemiology 2013, 28, 317-328, doi:10.1007/s10654-013-9795-x
2. Mentella, M.C.; Scaldaferri, F.; Ricci, C.; Gasbarrini, A.; Miggiano, G.A.D. Cancer and Mediterranean Diet: A Review. Nutrients 2019, 11, 2059. https://doi.org/10.3390/nu11092059
3. Crudele, L.; Piccinin, E.; Moschetta, A. Visceral Adiposity and Cancer: Role in Pathogenesis and Prognosis. Nutrients 2021, 13, 2101. https://doi.org/10.3390/nu13062101
4. De Matteis, C.; Crudele, L.; Battaglia, S.; Loconte, T.; Rotondo, A.; Ferrulli, R.; Gadaleta, R.M.; Piazzolla, G.; Suppressa, P.; Sabbà, C.; Cariello, M.; Moschetta, A. Identification of a Novel Score for Adherence to the Mediterranean Diet That Is Inversely Associated with Visceral Adiposity and Cardiovascular Risk: The Chrono Med Diet Score (CMDS). Nutrients 2023, 15, 1910. https://doi.org/10.3390/nu15081910.
5. Panagiotakos, D.B.; Pitsavos, C.; Arvaniti, F.; Stefanadis, C. Adherence to the Mediterranean food pattern predicts the prevalence of hypertension, hypercholesterolemia, diabetes and obesity, among healthy adults; the accuracy of the MedDietScore. Prev. Med. 2007, 44, 335–340. https://doi.org/10.1016/j.ypmed.2006.12.009.

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

Small intestinal bacterial overgrowth (SIBO) is a commonly diagnosed finding in diverse conditions ranging from DGBI to GI motility, connective tissue and neurodegenerative disorders (1). A wide spectrum of signs and symptoms have been attributed to SIBO (1,2). Diagnosis is achieved either by direct culture of duodenal aspirate or indirectly, by demonstrating exhaled fermentation gases with ingested sugars, such as glucose or lactulose (3,4). In the breath tests used for carbohydrate intolerances, the symptoms provoked are at least as important for the diagnostic interpretation as the measured gas concentrations. However, the symptoms generated during SIBO breath tests are neither evaluated nor mentioned in most testing guidelines. SIBO exists in asymptomatic populations and the association with symptoms remains uncertain (1,2).

Aims & Methods

We examined the acute relationship between breath gases and the symptoms generated during glucose breath tests in DGBI. A standardised breath test with glucose (50g in 150ml water) was performed after a 24-hour low-FODMAP diet and >8-hour fast. Exhaled hydrogen and methane concentrations were measured and symptom assessments (composite symptom index score, SI used for intolerance breath tests)(5) were performed every 15 minutes for 2 hours in 790 male (30%) and female patients of average age 40.0 years referred to our gastroenterology practice with DGBI (Rome 4 criteria). Breath gas concentration thresholds of >20ppm and >10ppm above baseline were considered positive tests for hydrogen and methane, respectively.

Results

Overall, 59 (7.5%) and 111 (14.1%) DGBI patients were SIBO positive using the hydrogen and methane thresholds, respectively. The composite SI was positive in 208 (26.3%) of patients. The most common individual symptoms were fullness, nausea, tiredness, headache (each in >30% of patients), followed by bloating, flatulence, abdominal cramps or pain, GORD and problems concentrating (each in 20-30% of patients). A positive SI with a negative hydrogen test was seen in 151 (19.1%) of DGBI patients, in 108 (13.0%) with a negative methane test and in 55 (7.0%) with both negative hydrogen and methane tests. A negative SI occurred in 2.4% of patients if either of the gas tests was positive.

Conclusion

During the glucose SIBO breath test, positive gas results and evoked symptoms are closely associated. However, glucose frequently provokes symptoms in DGBI patients with negative hydrogen and/or methane breath test results. This may be due to a discrepancy between breath and intestinal gases, production of gases beyond hydrogen and methane, or the induction of symptoms by glucose or its metabolites via alternative mechanisms.

References

1. Quigley EMM, et al. Expert Review. Gastroenterology 2020;159:1526-1532.
2. Bushyhead D, et al. Gastroenterology 2022;163:593-607.
3. Losurdo G, et al. J Neurogastroenterol Motil 2020;26:16-28.
4. Tansel A, et al. Clin Transl Gastroenterol 2023;14:e00567.
5. Wilder-Smith CH, et al. Aliment Pharmacol Ther 2013;37:1074-83.