title: Levothyroxine therapy and impaired clearance are the strongest contributors to small intestinal bacterial overgrowth: Results of a retrospective cohort study.
abstract: OBJECTIVE
  To identify a set of contributors, and weight and rank them on a pathophysiological basis.
  
  
  METHODS
  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 theχ2test, Student'st-test and logistic regression models.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Thorsten Brechmann, Andre Sperlbaum, Wolff Schmiegel, Department of Gastroenterology and Hepatology, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil GmbH, Ruhr-University Bochum, 44789 Bochum, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Brechmann
authors.affiliation: Thorsten Brechmann, Andre Sperlbaum, Wolff Schmiegel, Department of Gastroenterology and Hepatology, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil GmbH, Ruhr-University Bochum, 44789 Bochum, Germany.
authors.forename: Andre
authors.initials: A
authors.lastname: Sperlbaum
authors.affiliation: Thorsten Brechmann, Andre Sperlbaum, Wolff Schmiegel, Department of Gastroenterology and Hepatology, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil GmbH, Ruhr-University Bochum, 44789 Bochum, Germany.
authors.forename: Wolff
authors.initials: W
authors.lastname: Schmiegel
mesh_terms: D000328:Adult; D000368:Aged; D001765:Blind Loop Syndrome / Q000139:chemically induced / Q000209:etiology* / Q000503:physiopathology; D001944:Breath Tests; D015331:Cohort Studies; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000187:drug effects; D005769:Gastrointestinal Motility; D006801:Humans; D007037:Hypothyroidism / Q000150:complications / Q000188:drug therapy; D007421:Intestine, Small / Q000187:drug effects* / Q000382:microbiology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D013974:Thyroxine / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D013974:Thyroxine
keywords: Bacterial overgrowth syndrome; Hydrogen breath tests; Hypothyroidism; Immunosuppression; Intestinal motility