Retrospective Cohort Study
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World J Gastroenterol. Feb 7, 2017; 23(5): 842-852
Published online Feb 7, 2017. doi: 10.3748/wjg.v23.i5.842
Levothyroxine therapy and impaired clearance are the strongest contributors to small intestinal bacterial overgrowth: Results of a retrospective cohort study
Thorsten Brechmann, Andre Sperlbaum, Wolff Schmiegel
Thorsten Brechmann, Andre Sperlbaum, Wolff Schmiegel, Department of Gastroenterology and Hepatology, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil GmbH, Ruhr-University Bochum, 44789 Bochum, Germany
Author contributions: Brechmann T was guarantor of the article; contributed to conception and design of the study, data analysis and interpretation, supervision, drafting the manuscript; Sperlbaum A contributed to conducting the study, acquisition of data, analysis and interpretation; Schmiegel W contributed to supervision, revision of the manuscript, support in terms of gastroenterology; all authors approved the final manuscript.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of the Ruhr-University Bochum (Registration number: 4864-13).
Conflict-of-interest statement: The authors declare that there is no actual or potential conflict of interest related to the work.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Thorsten Brechmann, MD, Department of Gastroenterology and Hepatology, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil GmbH, Ruhr-University Bochum, Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany.
Telephone: +49-234-3023411 Fax: +49-234-3026707
Received: August 26, 2016
Peer-review started: August 28, 2016
First decision: October 20, 2016
Revised: October 22, 2016
Accepted: November 16, 2016
Article in press: November 16, 2016
Published online: February 7, 2017

To identify a set of contributors, and weight and rank them on a pathophysiological basis.


Patients who have undergone a lactulose or glucose hydrogen breath test to rule out small intestinal bacterial overgrowth (SIBO) for various clinical symptoms, including diarrhoea, weight loss, abdominal pain, cramping or bloating, were seen as eligible for inclusion in a retrospective single-centre study. Clinical data such as co-morbidities, medication, laboratory parameters and other possible risk factors have been identified from the electronic data system. Cases lacking or with substantially incomplete clinical data were excluded from the analysis. Suspected contributors were summarised under four different pathophysiological pathways (impaired gastric acid barrier, impaired intestinal clearance, immunosuppression and miscellaneous factors including thyroid gland variables) and investigated using the χ2 test, Student’s t-test and logistic regression models.


A total of 1809 patients who had undergone hydrogen breath testing were analysed. Impairment of the gastric acid barrier (gastrectomy, odds ratio: OR = 3.5, PPI therapy OR = 1.4), impairment of intestinal clearance (any resecting gastric surgery OR = 2.6, any colonic resection OR = 1.9, stenosis OR = 3.4, gastroparesis OR = 3.4, neuropathy 2.2), immunological factors (any drug-induced immunosuppression OR = 1.8), altered thyroid gland metabolism (hypothyroidism OR = 2.6, levothyroxine therapy OR = 3.0) and diabetes mellitus (OR = 1.9) were associated significantly to SIBO. Any abdominal surgery, ileocecal resection, vagotomy or IgA-deficiency did not have any influence, and a history of appendectomy decreased the risk of SIBO. Multivariate analysis revealed gastric surgery, stenoses, medical immunosuppression and levothyroxine to be the strongest predictors. Levothyroxine therapy was the strongest contributor in a simplified model (OR = 3.0).


The most important contributors for the development of SIBO in ascending order are immunosuppression, impairment of intestinal clearance and levothyroxine use, but they do not sufficiently explain its emergence.

Keywords: Bacterial overgrowth syndrome, Hydrogen breath tests, Immunosuppression, Intestinal motility, Hypothyroidism

Core tip: Several contributors to small intestinal overgrowth have been described, but the impact of particular risk factors is poorly understood. We aimed to determine the influence of several pathomechanisms, such as impaired gastric acid barrier function, impaired intestinal clearance, impairment of defence mechanisms and miscellaneous factors, as well as to weight and rank a large set of potential contributors by means of a retrospective cohort study of 1809 consecutive patients who had undergone a hydrogen breath test to rule out small intestinal bacterial overgrowth. Overall, levothyroxine therapy, impaired intestinal clearance and immunosuppression are the strongest contributors, while an impaired gastric acid barrier only plays a minor role.