Year 2025 / Volume 117 / Number 8
Original
Small intestine bacterial overgrowth breath test does not predict symptom severity in gut-brain interaction disorders: role of anxiety, depression and inflammatory biomarkers

433-440

DOI: 10.17235/reed.2025.11157/2025

Sandra Izquierdo Santervás, Carlos Maroto Martín, Aida Fiz-López, José Antonio Garrote Adrados, Sara Cuesta Sancho, David Bernardo Ordiz, Eduardo Arranz Sanz, Luis Fernández-Salazar,

Abstract
Background: the high prevalence of disorders of the gut-brain interaction (DGBI), the availability of breath tests for the diagnosis of small intestine bacterial overgrowth (SIBO) together with some confusion about the concept of SIBO have led to an increase in the number of SIBO diagnoses. Objective: this study aimed to analyze factors associated with the severity of gastrointestinal symptoms in patients undergoing a SIBO breath test. Methods: a cross-sectional observational study including 70 patients who underwent a SIBO test with lactitol and completed questionnaires including the ROME IV criteria for irritable bowel syndrome (IBS), the Irritable Bowel Syndrome Severity Score (IBSSS), and HAD anxiety and depression scales. Additionally, blood levels of histamine, citrulline, ghrelin, intestinal-fatty acid binding protein (I-FABP) and transient receptor potential cation channel subfamily V, member 1 (TRPV-1) were measured. Results: the mean age of the cohort was 45 ± 16 years and 70 % were female. Abdominal pain and/or abdominal distension were present in 85 % of patients and 44 % met IBS Rome IV criteria. IBSSS total score correlated with age (-0.354, p < 0.001), HAD-A (0.391, p < 0.001) and HAD-D (0.409, p < 0.001) scores, and histamine levels (0.279, p = 0.019). Abdominal pain correlated with levels of histamine (0.320, p < 0.05; 0.282, p < 0.05) and ghrelin (0.252, p < 0.05, 0.347, p < 0.05), while abdominal distension correlated with I-FABP levels (0.314, p < 0.05). The SIBO test was positive in 75 % but did not correlate with symptom severity. Conclusion: this study unveiled some factors associated with the severity of abdominal pain and distension such as age, auto-perceived anxiety and depression and some biomarkers but not the SIBO test result.
Lay Summary
The small intestinal bacterial overgrowth breath test is proposed for the management of some gut-brain interaction disorders such as irritable bowel syndrome and symptoms like flatulence. The wide availability and overdemand of small intestinal bacterial overgrowth breath tests may lead to an increase in the number of diagnoses and antibiotic prescriptions. This study aimed to analyze the factors associated with the severity of gastrointestinal symptoms in patients who underwent a small intestinal bacterial overgrowth breath test in clinical practice. The study included 70 patients who underwent a small intestinal bacterial overgrowth test, as well as questionnaires on gastrointestinal symptoms related to their irritable bowel syndrome and scales assessing anxiety and depression. Additionally, blood levels of various molecules considered markers of inflammation, such as citrulline, ghrelin, histamine, Intestinal-Fatty Acid Binding Protein (I-FABP) and Transient Receptor Potential Cation Channel Subfamily V and Member 1 (TRPV-1) were measured. In patients who underwent a SIBO breath test due to clinical practice, the intensity of symptoms was not associated with the results of the test but instead with age and the patient's auto-perception of anxiety and depression. Molecules such as histamine, ghrelin and I-FABP correlated with the intensity of some gastrointestinal symptoms in this group of patients.
New comment
Comments
No comments for this article
References
1. Flores-Arriaga, J., et al., Prevalence and description of disorders of gut-brain interaction in Spain according to the results of the Rome Foundation Global Epidemiology Study. Neurogastroenterol Motil, 2023. 35(6): p. e14582.
2. Rezaie, A., et al., Hydrogen and Methane-Based Breath Testing in Gastrointestinal Disorders: The North American Consensus. Am J Gastroenterol, 2017. 112(5): p. 775-784.
3. Hammer, H.F., et al., European guideline on indications, performance, and clinical impact of hydrogen and methane breath tests in adult and pediatric patients: European Association for Gastroenterology, Endoscopy and Nutrition, European Society of Neurogastroenterology and Motility, and European Society for Paediatric Gastroenterology Hepatology and Nutrition consensus. United European Gastroenterol J, 2022. 10(1): p. 15-40.
4. Ghoshal, U.C., et al., Asian-Pacific consensus on small intestinal bacterial overgrowth in gastrointestinal disorders: An initiative of the Indian Neurogastroenterology and Motility Association. Indian J Gastroenterol, 2022. 41(5): p. 483-507.
5. Pimentel, M., et al., ACG Clinical Guideline: Small Intestinal Bacterial Overgrowth. Am J Gastroenterol, 2020. 115(2): p. 165-178.
6. Martín Domínguez, V., C. Malagelada, and C. Santander, Small intestinal bacterial overgrowth. A position paper of ASENEM-SEPD. Rev Esp Enferm Dig, 2023. 115(12): p. 679-681.
7. Kashyap, P., et al., Critical appraisal of the SIBO hypothesis and breath testing: A clinical practice update endorsed by the European society of neurogastroenterology and motility (ESNM) and the American neurogastroenterology and motility society (ANMS). Neurogastroenterol Motil, 2024. 36(6): p. e14817.
8. Lee, C., et al., The Increased Level of Depression and Anxiety in Irritable Bowel Syndrome Patients Compared with Healthy Controls: Systematic Review and Meta-analysis. J Neurogastroenterol Motil, 2017. 23(3): p. 349-362.
9. Esterita, T., et al., Association of Functional Dyspepsia with Depression and Anxiety: A Systematic Review. J Gastrointestin Liver Dis, 2021. 30(2): p. 259-266.
10. Vasant, D.H., et al., British Society of Gastroenterology guidelines on the management of irritable bowel syndrome. Gut, 2021. 70(7): p. 1214-1240.
11. Maric, S., et al., Citrulline, Biomarker of Enterocyte Functional Mass and Dietary Supplement. Metabolism, Transport, and Current Evidence for Clinical Use. Nutrients, 2021. 13(8).
12. Wu, W., et al., Ghrelin in Focus: Dissecting Its Critical Roles in Gastrointestinal Pathologies and Therapies. Curr Issues Mol Biol, 2024. 46(1): p. 948-964.
13. Klooker, T.K., et al., The mast cell stabiliser ketotifen decreases visceral hypersensitivity and improves intestinal symptoms in patients with irritable bowel syndrome. Gut, 2010. 59(9): p. 1213-21.
14. Decraecker, L., et al., Treatment of non-constipated irritable bowel syndrome with the histamine 1 receptor antagonist ebastine: a randomised, double-blind, placebo-controlled trial. Gut, 2024. 73(3): p. 459-469.
15. Linsalata, M., et al., Noninvasive biomarkers of gut barrier function identify two subtypes of patients suffering from diarrhoea predominant-IBS: a case-control study. BMC Gastroenterol, 2018. 18(1): p. 167.
16. Prospero, L., et al., Psychological and Gastrointestinal Symptoms of Patients with Irritable Bowel Syndrome Undergoing a Low-FODMAP Diet: The Role of the Intestinal Barrier. Nutrients, 2021. 13(7).
17. Logan, M., et al., Intestinal fatty acid binding protein is a disease biomarker in paediatric coeliac disease and Crohn's disease. BMC Gastroenterol, 2022. 22(1): p. 260.
18. Wouters, M.M., et al., Histamine Receptor H1-Mediated Sensitization of TRPV1 Mediates Visceral Hypersensitivity and Symptoms in Patients With Irritable Bowel Syndrome. Gastroenterology, 2016. 150(4): p. 875-87.e9.
19. Drossman, D.A. and W.L. Hasler, Rome IV-Functional GI Disorders: Disorders of Gut-Brain Interaction. Gastroenterology, 2016. 150(6): p. 1257-61.
20. Almansa, C., et al., Translation, cultural adaptation and validation of a Spanish version of the Irritable Bowel Syndrome Severity Score. Rev Esp Enferm Dig, 2011. 103(12): p. 612-8.
21. Zigmond, A.S. and R.P. Snaith, The hospital anxiety and depression scale. Acta Psychiatr Scand, 1983. 67(6): p. 361-70.
22. Nahon, S., et al., Risk factors of anxiety and depression in inflammatory bowel disease. Inflamm Bowel Dis, 2012. 18(11): p. 2086-91.
23. Mearin, F., et al., Bowel Disorders. Gastroenterology, 2016.
24. Sperber, A.D., Highlights of the Findings From the Rome Foundation Global Epidemiology Study. Gastroenterol Hepatol (N Y), 2023. 19(9): p. 564-567.
25. Mishima, Y. and S. Ishihara, Molecular Mechanisms of Microbiota-Mediated Pathology in Irritable Bowel Syndrome. Int J Mol Sci, 2020. 21(22).
26. Arasaradnam, R.P., et al., Guidelines for the investigation of chronic diarrhoea in adults: British Society of Gastroenterology, 3rd edition. Gut, 2018. 67(8): p. 1380-1399.
27. Savarino, E., et al., Functional bowel disorders with diarrhoea: Clinical guidelines of the United European Gastroenterology and European Society for Neurogastroenterology and Motility. United European Gastroenterol J, 2022. 10(6): p. 556-584.
28. Lacy, B.E., et al., ACG Clinical Guideline: Management of Irritable Bowel Syndrome. Am J Gastroenterol, 2021. 116(1): p. 17-44.
29. Pimentel, M., E.J. Chow, and H.C. Lin, Normalization of lactulose breath testing correlates with symptom improvement in irritable bowel syndrome. a double-blind, randomized, placebo-controlled study. Am J Gastroenterol, 2003. 98(2): p. 412-9.
30. Black, C.J., et al., Functional gastrointestinal disorders: advances in understanding and management. Lancet, 2020. 396(10263): p. 1664-1674.
31. Chen, M., et al., Neurotransmitter and Intestinal Interactions: Focus on the Microbiota-Gut-Brain Axis in Irritable Bowel Syndrome. Front Endocrinol (Lausanne), 2022. 13: p. 817100.
32. Maroto, C., et al., Plasma levels of intestinal fatty-acid binding protein (I-FABP), abdominal distension and hydrogen concentration after lactitol small intestinal bacterial overgrowth (SIBO) test. Rev Esp Enferm Dig, 2023. 115(12): p. 727-728.
33. Mir, B.A., et al., Emerging Biomarkers for Screening and Management of Celiac Disease. Biomed Res Int, 2022. 2022: p. 2756242.
34. Saad, R.J. and W.D. Chey, Breath testing for small intestinal bacterial overgrowth: maximizing test accuracy. Clin Gastroenterol Hepatol, 2014. 12(12): p. 1964-72; quiz e119-20.
35. Lacy, B.E., D. Cangemi, and M. Vazquez-Roque, Management of Chronic Abdominal Distension and Bloating. Clin Gastroenterol Hepatol, 2021. 19(2): p. 219-231.e1.
Related articles
Citation tools
Izquierdo Santervás S, Maroto Martín C, Fiz-López A, Garrote Adrados J, Cuesta Sancho S, Bernardo Ordiz D, et all. Small intestine bacterial overgrowth breath test does not predict symptom severity in gut-brain interaction disorders: role of anxiety, depression and inflammatory biomarkers. 11157/2025


Download to a citation manager

Download the citation for this article by clicking on one of the following citation managers:

Metrics
This article has received 9 visits.
This article has been downloaded 1 times.

Statistics from Dimensions


Statistics from Plum Analytics

Publication history

Received: 15/02/2025

Accepted: 03/04/2025

Online First: 25/04/2025

Published: 24/07/2025

Article revision time: 43 days

Article Online First time: 69 days

Article editing time: 159 days


Share
This article hasn't been rated yet.
Reader rating:
Valora este artículo:




Asociación Española de Ecografía Digestiva Sociedad Española de Endoscopia Digestiva Sociedad Española de Patología Digestiva
The Spanish Journal of Gastroenterology is the official organ of the Sociedad Española de Patología Digestiva, the Sociedad Española de Endoscopia Digestiva and the Asociación Española de Ecografía Digestiva
Cookie policy Privacy Policy Legal Notice © Copyright 2025 y Creative Commons. The Spanish Journal of Gastroenterology