Suppression of gastric acid secretion in patients with gastroesophageal reflux disease results in gastric bacterial overgrowth and deconjugation of bile acids


The aim of this study was to test the hypothesis that gastric bacterial overgrowth is a side effect of acid suppression therapy in patients with gastroesophageal reflux disease (GERD) and that the bacteria-contaminated gastric milieu is responsible for an increased amount of deconjugated bile acids. Thirty patients with GERD who were treated with 40 mg of omeprazole for at least 3 months and 10 patients with GERD who were off medication for at least 2 weeks were studied. At the time of upper endoscopy, 10 ml of gastric fluid was aspirated and analyzed for bacterial growth and bile acids. Bacterial over-growth was defined by the presence of more than 1000 bacteria/ml. Bile acids were quantified via high-performance liquid chromatography. Eleven of the 30 patients taking omeprazole had bacterial over-growth compared to one of the 10 control patients. The median pH in the bacteria-positive patients was 5.3 compared to 2.6 in those who were free of bacteria and 3.5 in the control patients who were off medication. Bacterial overgrowth only occurred when the pH was >3.8. The ratio of conjugated to unconjugated bile acids changed from 4:1 in the patients without bacterial overgrowth to 1:3 in those with bacterial growth greater than 1000/ml. Proton pump inhibitor therapy in patients with GERD results in a high prevalence of gastric bacterial overgrowth. The presence of bacterial overgrowth markedly increases the concentration of unconjugated bile acids. These findings may have implications in the pathophysiology of gastroesophageal mucosal injury.

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  1. 1.

    Sharma BK, Walt RP, Pounder RE, Gomes MD, Wood EC, Logan LH. Optimal dose of oral omeprazole for maximal 24 hour decrease of intragastric acidity. Gut 1984;25:957–964.

    PubMed  CAS  Google Scholar 

  2. 2.

    Thorens J, Froehlich F, Schwizer W, et al.. Bacterial over- growth during treatment with omeprazole compared with cimetidine: A prospective randomised double blind study. Gut 1996;39:54–59.

    PubMed  CAS  Google Scholar 

  3. 3.

    Karmeli Y, Stalnikowitz R, Elialdm R, Rahav G. Conventional dose of omeprazole alters gastric flora. Dig Dis Sci 1995;40:2070–2073.

    PubMed  Article  CAS  Google Scholar 

  4. 4.

    Domellof L, Reddy BS, Weisburger JH. Microflora and de- conjugation of bile acids in alkaline reflux after partial gas- trectomy. Am J Surg 1980;140:291–295.

    PubMed  Article  CAS  Google Scholar 

  5. 5.

    Stockbruegger RW, Cotton PB, Menon GG, et al.. Pernicious anaemia, intragastric bacterial overgrowth, and possible con- sequences. Scand J Gastroenterol 1984;19:355–364.

    PubMed  CAS  Google Scholar 

  6. 6.

    Freston JW. Long-term acid control and proton pump in- hibitors: Interactions and safety issues in perspective. Am J Gastroenterol 1997;92:51S-57S.

    PubMed  CAS  Google Scholar 

  7. 7.

    Hill M. Normal and pathological microbial flora of the upper gastrointestinal tract. Scand J Gastroenterol (Suppl) 1985; 111:1–6.

    CAS  Google Scholar 

  8. 8.

    Sherman P, Lichtman S. Small bowel bacterial overgrowth syndrome [Review]. Dig Dis 1987;5:157–171.

    PubMed  CAS  Google Scholar 

  9. 9.

    Driks MR, Craven DE, Celli BR, et al.. Nocosomial pneumo- nia in intubated patients given sucralfate as compared with antacids or histamine type 2 blockers. The role of gastric col- onization. N Engl J Med 1987;317:1376–1382.

    PubMed  CAS  Article  Google Scholar 

  10. 10.

    Reed PI, Smith PL, Haines K, House FR, Walters CL. Gas- tric juice N-nitrosamines in health and gastroduodenal dis- ease. Lancet 1981;2:550–552.

    PubMed  Article  CAS  Google Scholar 

  11. 11.

    Kauer WK, Peters JH, DeMeester TR, Ireland AP, Bremner CG, Hagen JA. Mixed reflux of gastric and duodenal juices is more harmful to the esophagus than gastric juice alone. The need for surgical therapy re-emphasized [discussion]. Ann Surg 1995;222:525–531.

    PubMed  CAS  Article  Google Scholar 

  12. 12.

    Gotley DC, Morgan AP, Cooper MJ. Bile acid concentrations in the refluxate of patients with reflux oesophagitis. Br J Surg 1988;75:587–590.

    PubMed  Article  CAS  Google Scholar 

  13. 13.

    Iftikhar SY, Ledingham S, Steele RJ, et al.. Bile reflux in columnar-lined Barrett’s oesophagus. Ann R Coll Surg Engl 1993;75:411–416.

    PubMed  CAS  Google Scholar 

  14. 14.

    Armstrong D, Rytina ER, Murphy GM, Dowling RH. Gastric mucosal toxicity of duodenal juice constituents in the rat. Acute studies using ex vivo rat gastric chamber model. Dig Dis Sci 1994;39:327–339.

    PubMed  Article  CAS  Google Scholar 

  15. 15.

    Bergey DH. Bergey’s Manual of Determinative Bacteriology. Baltimore: Williams & Wilkins, 1994.

    Google Scholar 

  16. 16.

    Nehra D, Howell P, Pye JK, Beynon J. Assessment of com- bined bile acid and pH profiles using an automated sampling device in gastro-oesophageal reflux disease. Br J Surg 1998; 85:134–137.

    PubMed  Article  CAS  Google Scholar 

  17. 17.

    Nehra D, Howell P, Williams CP, Pye JK, Beynon J. Toxic bile acids in gastro-oesophageal reflux disease: influence of gastric acidity. Gut 1999;44:598–602.

    PubMed  CAS  Article  Google Scholar 

  18. 18.

    Kivilaasko E, Fromm D, Silen W. Effect of bile acids and re- lated compounds on isolated esuphageal mucosa. Surgery 1989;87:280–285.

    Google Scholar 

  19. 19.

    Huang XP, Fan XT, Desjeux JF, Castagna M. Bile acids, non-phorbol-ester-type tumor promoters, stimulate the phosphorylation of protein kinase C substrates in human platelets and colon cell line HT29. Int J Cancer 1992;52:444–450.

    PubMed  Article  CAS  Google Scholar 

  20. 20.

    Hirano F, Tanada H, Makino Y, et al.. Induction of the trans- cription factor AP-1 in cultured human colon adenocarcinoma cells following exposure to bile acids. Carcinogenesis 1996;17:427–433.

    PubMed  Article  CAS  Google Scholar 

  21. 21.

    Zhang F, Subbaramaiah K, Altorki N, Dannenberg AJ. Dihy- droxy bile acids activate the transcription of cyclooxygenase-2. J Biol Chem 1998;273.:2424–3428.

    PubMed  Article  Google Scholar 

  22. 22.

    Theisen J, Danenberg K, DeMeester TR, et al.. Effect of acid and bile salts on COX-2 gene expression on an esophageal adenocarcinoma cell line [abstr]. Proc Am Assoc Cancer Res 1999;40:505.

    Google Scholar 

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Correspondence to Jeffrey H. Peters M.D..

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Theisen, J., Nehra, D., Citron, D. et al. Suppression of gastric acid secretion in patients with gastroesophageal reflux disease results in gastric bacterial overgrowth and deconjugation of bile acids. J Gastrointest Surg 4, 50–54 (2000).

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Key words

  • Bacterial overgrowth
  • omeprazole
  • deconjugation