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Erschienen in: Digestive Diseases and Sciences 1/2022

03.02.2021 | Original Article

Effects of Proton Pump Inhibitors on the Small Bowel and Stool Microbiomes

verfasst von: Stacy Weitsman, Shreya Celly, Gabriela Leite, Ruchi Mathur, Rashin Sedighi, Gillian M. Barlow, Walter Morales, Maritza Sanchez, Gonzalo Parodi, Maria Jesus Villanueva-Millan, Ali Rezaie, Mark Pimentel

Erschienen in: Digestive Diseases and Sciences | Ausgabe 1/2022

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Abstract

Background

Proton pump inhibitor (PPI) use is extremely common. PPIs have been suggested to affect the gut microbiome, and increase risks of Clostridium difficile infection and small intestinal bacterial overgrowth (SIBO). However, existing data are based on stool analyses and PPIs act on the foregut.

Aims

To compare the duodenal and stool microbiomes in PPI and non-PPI users.

Methods

Consecutive subjects presenting for upper endoscopy without colonoscopy were recruited. Current antibiotic users were excluded. Subjects taking PPI were age- and gender-matched 1:2 to non-PPI controls. Subjects completed medical history questionnaires, and duodenal aspirates were collected using a validated protected catheter. A subset also provided stool samples. Duodenal and stool microbiomes were analyzed by 16S rRNA sequencing.

Results

The duodenal microbiome exhibited no phylum-level differences between PPI (N = 59) and non-PPI subjects (N = 118), but demonstrated significantly higher relative abundances of families Campylobacteraceae (3.13-fold, FDR P value < 0.01) and Bifidobacteriaceae (2.9-fold, FDR P value < 0.01), and lower relative abundance of Clostridiaceae (88.24-fold, FDR P value < 0.0001), in PPI subjects. SIBO rates were not significantly different between groups, whether defined by culture (> 103 CFU/ml) or 16S sequencing, nor between subjects taking different PPIs. The stool microbiome exhibited significantly higher abundance of family Streptococcaceae (2.14-fold, P = 0.003), and lower Clostridiaceae (2.60-fold, FDR P value = 8.61E-13), in PPI (N = 22) versus non-PPI (N = 47) subjects.

Conclusions

These findings suggest that PPI use is not associated with higher rates of SIBO. Relative abundance of Clostridiaceae was reduced in both the duodenal and stool microbiomes, and Streptococcaceae was increased in stool. The clinical implications of these findings are unknown.
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Literatur
1.
Zurück zum Zitat Halfdanarson OO, Pottegard A, Bjornsson ES et al. Proton-pump inhibitors among adults: a nationwide drug-utilization study. Ther Adv Gastroenterol. 2018;11:1–11CrossRef Halfdanarson OO, Pottegard A, Bjornsson ES et al. Proton-pump inhibitors among adults: a nationwide drug-utilization study. Ther Adv Gastroenterol. 2018;11:1–11CrossRef
2.
Zurück zum Zitat Jaynes M, Kumar AB. The risks of long-term use of proton pump inhibitors: a critical review. Ther Adv Drug Saf. 2019;10:1–13CrossRef Jaynes M, Kumar AB. The risks of long-term use of proton pump inhibitors: a critical review. Ther Adv Drug Saf. 2019;10:1–13CrossRef
3.
Zurück zum Zitat Moayyedi P, Eikelboom JW, Bosch J et al. Safety of proton pump inhibitors based on a large, multi-year, randomized trial of patients receiving rivaroxaban or aspirin. Gastroenterology. 2019;157:e682CrossRef Moayyedi P, Eikelboom JW, Bosch J et al. Safety of proton pump inhibitors based on a large, multi-year, randomized trial of patients receiving rivaroxaban or aspirin. Gastroenterology. 2019;157:e682CrossRef
4.
Zurück zum Zitat Janarthanan S, Ditah I, Adler DG, Ehrinpreis MN. Clostridium difficile-associated diarrhea and proton pump inhibitor therapy: a meta-analysis. Am J Gastroenterol. 2012;107:1001–1010CrossRef Janarthanan S, Ditah I, Adler DG, Ehrinpreis MN. Clostridium difficile-associated diarrhea and proton pump inhibitor therapy: a meta-analysis. Am J Gastroenterol. 2012;107:1001–1010CrossRef
5.
Zurück zum Zitat Lombardo L, Foti M, Ruggia O, Chiecchio A. Increased incidence of small intestinal bacterial overgrowth during proton pump inhibitor therapy. Clin Gastroenterol Hepatol. 2010;8:504–508CrossRef Lombardo L, Foti M, Ruggia O, Chiecchio A. Increased incidence of small intestinal bacterial overgrowth during proton pump inhibitor therapy. Clin Gastroenterol Hepatol. 2010;8:504–508CrossRef
6.
Zurück zum Zitat Erdogan A, Rao SS, Gulley D, Jacobs C, Lee YY, Badger C. Small intestinal bacterial overgrowth: duodenal aspiration vs glucose breath test. Neurogastroenterol Motil. 2015;27:481–489CrossRef Erdogan A, Rao SS, Gulley D, Jacobs C, Lee YY, Badger C. Small intestinal bacterial overgrowth: duodenal aspiration vs glucose breath test. Neurogastroenterol Motil. 2015;27:481–489CrossRef
7.
Zurück zum Zitat Pimentel M. The prevalence of small intestinal bacterial overgrowth in irritable bowel syndrome: IBS vs healthy controls (not historical definitions). Gut. 2008;57:1334–1335 (author reply 1335).PubMed Pimentel M. The prevalence of small intestinal bacterial overgrowth in irritable bowel syndrome: IBS vs healthy controls (not historical definitions). Gut. 2008;57:1334–1335 (author reply 1335).PubMed
8.
Zurück zum Zitat Majewski M, McCallum RW. Results of small intestinal bacterial overgrowth testing in irritable bowel syndrome patients: clinical profiles and effects of antibiotic trial. Adv Med Sci. 2007;52:139–142PubMed Majewski M, McCallum RW. Results of small intestinal bacterial overgrowth testing in irritable bowel syndrome patients: clinical profiles and effects of antibiotic trial. Adv Med Sci. 2007;52:139–142PubMed
9.
Zurück zum Zitat Fialho A, Fialho A, Thota P, McCullough AJ, Shen B. Small intestinal bacterial overgrowth is associated with non-alcoholic fatty liver disease. J Gastrointest Liver Dis. 2016;25:159–165CrossRef Fialho A, Fialho A, Thota P, McCullough AJ, Shen B. Small intestinal bacterial overgrowth is associated with non-alcoholic fatty liver disease. J Gastrointest Liver Dis. 2016;25:159–165CrossRef
10.
Zurück zum Zitat Sanchez-Montes C, Ortiz V, Bastida G et al. Small intestinal bacterial overgrowth in inactive Crohn’s disease: influence of thiopurine and biological treatment. World J Gastroenterol. 2014;20:13999–14003CrossRef Sanchez-Montes C, Ortiz V, Bastida G et al. Small intestinal bacterial overgrowth in inactive Crohn’s disease: influence of thiopurine and biological treatment. World J Gastroenterol. 2014;20:13999–14003CrossRef
11.
Zurück zum Zitat Shah A, Talley NJ, Jones M et al. Small intestinal bacterial overgrowth in irritable bowel syndrome: a systematic review and meta-analysis of case-control studies. Am J Gastroenterol. 2020;115:190–201CrossRef Shah A, Talley NJ, Jones M et al. Small intestinal bacterial overgrowth in irritable bowel syndrome: a systematic review and meta-analysis of case-control studies. Am J Gastroenterol. 2020;115:190–201CrossRef
13.
Zurück zum Zitat Spiegel BM, Chey WD, Chang L. Bacterial overgrowth and irritable bowel syndrome: unifying hypothesis or a spurious consequence of proton pump inhibitors? Am J Gastroenterol. 2008;103:2972–2976CrossRef Spiegel BM, Chey WD, Chang L. Bacterial overgrowth and irritable bowel syndrome: unifying hypothesis or a spurious consequence of proton pump inhibitors? Am J Gastroenterol. 2008;103:2972–2976CrossRef
14.
Zurück zum Zitat Leite GGS, Morales W, Weitsman S et al. Optimizing microbiome sequencing for small intestinal aspirates: validation of novel techniques through the REIMAGINE study. BMC Microbiol. 2019;19:239CrossRef Leite GGS, Morales W, Weitsman S et al. Optimizing microbiome sequencing for small intestinal aspirates: validation of novel techniques through the REIMAGINE study. BMC Microbiol. 2019;19:239CrossRef
16.
Zurück zum Zitat Leite G, Morales W, Weitsman S et al. The duodenal microbiome is altered in small intestinal bacterial overgrowth. PLoS ONE. 2020;15:e0234906CrossRef Leite G, Morales W, Weitsman S et al. The duodenal microbiome is altered in small intestinal bacterial overgrowth. PLoS ONE. 2020;15:e0234906CrossRef
17.
Zurück zum Zitat Klindworth A, Pruesse E, Schweer T et al. Evaluation of general 16S ribosomal RNA gene PCR primers for classical and next-generation sequencing-based diversity studies. Nucleic Acids Res. 2013;41:1CrossRef Klindworth A, Pruesse E, Schweer T et al. Evaluation of general 16S ribosomal RNA gene PCR primers for classical and next-generation sequencing-based diversity studies. Nucleic Acids Res. 2013;41:1CrossRef
18.
Zurück zum Zitat Rezaie A, Buresi M, Lembo A et al. Hydrogen and methane-based breath testing in gastrointestinal disorders: the North American consensus. Am J Gastroenterol. 2017;112:775–784CrossRef Rezaie A, Buresi M, Lembo A et al. Hydrogen and methane-based breath testing in gastrointestinal disorders: the North American consensus. Am J Gastroenterol. 2017;112:775–784CrossRef
19.
Zurück zum Zitat Pimentel M, Saad RJ, Long MD, Rao SSC. ACG Clinical Guideline: Small Intestinal Bacterial Overgrowth Am J Gastroenterol. 9000; E-published Ahead of Print. Pimentel M, Saad RJ, Long MD, Rao SSC. ACG Clinical Guideline: Small Intestinal Bacterial Overgrowth Am J Gastroenterol. 9000; E-published Ahead of Print.
20.
Zurück zum Zitat McMurdie PJ, Holmes S. Waste not, want not: why rarefying microbiome data is inadmissible. PLoS Comput Biol. 2014;10:e1003531CrossRef McMurdie PJ, Holmes S. Waste not, want not: why rarefying microbiome data is inadmissible. PLoS Comput Biol. 2014;10:e1003531CrossRef
21.
Zurück zum Zitat Weiss S, Xu ZZ, Peddada S et al. Normalization and microbial differential abundance strategies depend upon data characteristics. Microbiome. 2017;5:27CrossRef Weiss S, Xu ZZ, Peddada S et al. Normalization and microbial differential abundance strategies depend upon data characteristics. Microbiome. 2017;5:27CrossRef
22.
Zurück zum Zitat Weiss S, Van Treuren W, Lozupone C et al. Correlation detection strategies in microbial data sets vary widely in sensitivity and precision. ISME J. 2016;10:1669–1681CrossRef Weiss S, Van Treuren W, Lozupone C et al. Correlation detection strategies in microbial data sets vary widely in sensitivity and precision. ISME J. 2016;10:1669–1681CrossRef
23.
Zurück zum Zitat MacLaren R, Reynolds PM, Allen RR. Histamine-2 receptor antagonists vs proton pump inhibitors on gastrointestinal tract hemorrhage and infectious complications in the intensive care unit. JAMA Intern Med. 2014;174:564–574CrossRef MacLaren R, Reynolds PM, Allen RR. Histamine-2 receptor antagonists vs proton pump inhibitors on gastrointestinal tract hemorrhage and infectious complications in the intensive care unit. JAMA Intern Med. 2014;174:564–574CrossRef
24.
Zurück zum Zitat Alshamsi F, Belley-Cote E, Cook D et al. Efficacy and safety of proton pump inhibitors for stress ulcer prophylaxis in critically ill patients: a systematic review and meta-analysis of randomized trials. Crit Care. 2016;20:120CrossRef Alshamsi F, Belley-Cote E, Cook D et al. Efficacy and safety of proton pump inhibitors for stress ulcer prophylaxis in critically ill patients: a systematic review and meta-analysis of randomized trials. Crit Care. 2016;20:120CrossRef
25.
Zurück zum Zitat Biswal S. Proton pump inhibitors and risk for Clostridium difficile associated diarrhea. Biomed J. 2014;37:178–183CrossRef Biswal S. Proton pump inhibitors and risk for Clostridium difficile associated diarrhea. Biomed J. 2014;37:178–183CrossRef
26.
Zurück zum Zitat Arriola V, Tischendorf J, Musuuza J, Barker A, Rozelle JW, Safdar N. Assessing the risk of hospital-acquired clostridium difficile infection with proton pump inhibitor use: a meta-analysis. Infect Control Hosp Epidemiol. 2016;37:1408–1417CrossRef Arriola V, Tischendorf J, Musuuza J, Barker A, Rozelle JW, Safdar N. Assessing the risk of hospital-acquired clostridium difficile infection with proton pump inhibitor use: a meta-analysis. Infect Control Hosp Epidemiol. 2016;37:1408–1417CrossRef
27.
Zurück zum Zitat Choung RS, Locke GR, Schleck CD, Zinsmeister AR, Talley NJ. Associations between medication use and functional gastrointestinal disorders: a population-based study. Neurogastroenterol Motil. 2013;25:e298 Choung RS, Locke GR, Schleck CD, Zinsmeister AR, Talley NJ. Associations between medication use and functional gastrointestinal disorders: a population-based study. Neurogastroenterol Motil. 2013;25:e298
28.
Zurück zum Zitat Freedberg DE, Toussaint NC, Chen SP et al. Proton pump inhibitors alter specific taxa in the human gastrointestinal microbiome: a crossover trial. Gastroenterology. 2015;149:e889 Freedberg DE, Toussaint NC, Chen SP et al. Proton pump inhibitors alter specific taxa in the human gastrointestinal microbiome: a crossover trial. Gastroenterology. 2015;149:e889
30.
Zurück zum Zitat Vich Vila A, Collij V, Sanna S et al. Impact of commonly used drugs on the composition and metabolic function of the gut microbiota. Nat Commun. 2020;11:362CrossRef Vich Vila A, Collij V, Sanna S et al. Impact of commonly used drugs on the composition and metabolic function of the gut microbiota. Nat Commun. 2020;11:362CrossRef
31.
Zurück zum Zitat Liu S, Chen M, Wang Y et al. Effect of Veillonella parvula on the physiological activity of Streptococcus mutans. Arch Oral Biol. 2020;109:104578CrossRef Liu S, Chen M, Wang Y et al. Effect of Veillonella parvula on the physiological activity of Streptococcus mutans. Arch Oral Biol. 2020;109:104578CrossRef
Metadaten
Titel
Effects of Proton Pump Inhibitors on the Small Bowel and Stool Microbiomes
verfasst von
Stacy Weitsman
Shreya Celly
Gabriela Leite
Ruchi Mathur
Rashin Sedighi
Gillian M. Barlow
Walter Morales
Maritza Sanchez
Gonzalo Parodi
Maria Jesus Villanueva-Millan
Ali Rezaie
Mark Pimentel
Publikationsdatum
03.02.2021
Verlag
Springer US
Erschienen in
Digestive Diseases and Sciences / Ausgabe 1/2022
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-021-06857-y

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