Proton Pump Inhibitors Alter Specific Taxa in the Human Gastrointestinal Microbiome: A Crossover Trial

Freedberg, Daniel E.; Toussaint, Nora C.; Chen, Sway P.; Ratner, Adam J.; Whittier, Susan; Wang, Yichen; Wang, Harris H.; Abrams, Julian A.

doi:10.1053/j.gastro.2015.06.043

Cited by 263 publications

(257 citation statements)

References 32 publications

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“…5,17 Subsequent gut microbiota studies attributed the increased risk to unfavorable gut microbiota alterations caused by PPI use. [6][7][8] Human, animal and in vitro studies show an overlap between the specific gut microbiota alterations associated with PPI use (as found in Imhann et al Gut 2016) and the bacterial changes that lead to increased susceptibility to Clostridium difficile (as depicted in Fig. 2).…”

Section: Consequences Of Gut Microbiota Changes Caused By Medicationmentioning

confidence: 84%

“…Bacterial families associated with PPI use in 3 gut microbiota studies. [6][7][8] ; Consistent changes in 2 or all studies are marked in bold; NR D Not reported. Table 3.…”

Section: Other Commonly Used Drugs and The Gut Microbiotamentioning

confidence: 99%

“…[6][7][8][9][10][11] As a consequence, these types of medication could have an effect on the risk of developing enteric infections or gut inflammation, and they may also have an effect on host metabolism. [12][13][14][15] Susceptibility to enteric infections A well-known example of reduced enteric infection resistance through alteration of the gut microbiota caused by medication is the increased risk of Clostridium difficile infections after (repeated) treatment with antibiotics.…”

Section: Consequences Of Gut Microbiota Changes Caused By Medicationmentioning

confidence: 99%

“…One small scale intervention study investigating the role of PPI on the gut microbiota has already been performed. 7 …”

Section: Intervention Studiesmentioning

confidence: 99%

“…A small intervention study was published a few months before ours and a similar observational study was published in the same issue of Gut. 7,8 In Table 1, the bacterial alterations associated with PPI use from all 3 studies are presented at the family level. There are many similarities between the results of all 3 studies and, when associations at different taxonomical levels are taken into account (e.g.…”

mentioning

confidence: 99%

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The influence of proton pump inhibitors and other commonly used medication on the gut microbiota

et al. 2017

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Proton pump inhibitors (PPIs), used to treat gastro-esophageal reflux and prevent gastric ulcers, are among the most widely used drugs in the world. The use of PPIs is associated with an increased risk of enteric infections. Since the gut microbiota can, depending on composition, increase or decrease the risk of enteric infections, we investigated the effect of PPI-use on the gut microbiota. We discovered profound differences in the gut microbiota of PPI users: 20% of their bacterial taxa were statistically significantly altered compared with those of non-users. Moreover, we found that it is not only PPIs, but also antibiotics, antidepressants, statins and other commonly used medication were associated with distinct gut microbiota signatures. As a consequence, commonly used medications could affect how the gut microbiota resist enteric infections, promote or ameliorate gut inflammation, or change the host's metabolism. More studies are clearly needed to understand the role of commonly used medication in altering the gut microbiota as well as the subsequent health consequences.KEYWORDS gut microbiota; medication; proton pump inhibitors Proton pump inhibitors affect the gut microbiotaProton pump inhibitors (PPIs), used to treat gastroesophageal reflux and to prevent gastric ulcers, are among the most commonly used drugs in the world.1,2 In the Netherlands, one PPI alone (omeprazole) was the fourth most prescribed drug in 2015. In observational studies, the use of PPIs has been associated with an increased risk of enteric infections caused by Clostridium difficile, Salmonella spp., Shigella spp and Campylobacter spp. [3][4][5] Since the gut microbiota can, depending on composition, increase or decrease the risk of enteric infections, we investigated the effect of PPI use on the gut microbiota. 6 Using the 16S rRNA sequences of stool samples from 1815 individuals spanning 3 independent cohorts, we observed profound changes in the gut microbiota of PPI users. In PPI users the relative abundance of 20% of the bacterial taxa, whereof 18 bacterial families, was statistically significantly different (either increased or decreased) compared with abundances in samples from non-users. 6 Concurrently with our research, other research groups were also investigating the influence of PPIs on the gut microbiota. A small intervention study was published a few months before ours and a similar observational study was published in the same issue of Gut. 7,8 In Table 1, the bacterial alterations associated with PPI use from all 3 studies are presented at the family level. There are many similarities between the results of all 3 studies and, when associations at different taxonomical levels are taken into account (e.g. the decrease of order Clostridiales and increases of class Gammaproteobacteria and order Actinomycetales), a consistent profile of alterations in gut microbiota associated with PPI use emerges. Other commonly used drugs and the gut microbiotaTo ensure that our observed alterations in gut microbiota associated wi...

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Section: Consequences Of Gut Microbiota Changes Caused By Medicationmentioning

confidence: 84%

“…Bacterial families associated with PPI use in 3 gut microbiota studies. [6][7][8] ; Consistent changes in 2 or all studies are marked in bold; NR D Not reported. Table 3.…”

Section: Other Commonly Used Drugs and The Gut Microbiotamentioning

confidence: 99%

Section: Consequences Of Gut Microbiota Changes Caused By Medicationmentioning

confidence: 99%

“…One small scale intervention study investigating the role of PPI on the gut microbiota has already been performed. 7 …”

Section: Intervention Studiesmentioning

confidence: 99%

mentioning

confidence: 99%

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The influence of proton pump inhibitors and other commonly used medication on the gut microbiota

et al. 2017

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Association Between Acute Gastroenteritis and Continuous Use of Proton Pump Inhibitors During Winter Periods of Highest Circulation of Enteric Viruses

et al. 2019

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IMPORTANCE An increased risk of acute bacterial enteric infections has been reported among patients receiving proton pump inhibitor (PPI) therapy. The risk of acute gastroenteritis (AGE) of viral origin associated with continuous PPI exposure has been less studied. OBJECTIVE To investigate the association between continuous PPI therapy and AGE occurrence during winter epidemic periods when the circulation of enteric viruses is the highest. DESIGN, SETTING, AND PARTICIPANTS A matched cohort study was performed using a prospectively collected drug dispensing database from a large panel of community pharmacies in continental France. All patients recorded in the database during the 2015 to 2016 winter season, with documented age, sex, and use of an identifiable regular panel pharmacy, were eligible for the study. Each patient exposed to continuous PPI therapy was matched to 3 unexposed patients, according to year of birth, sex, and identifiable regular panel pharmacy. Analyses were performed between January 2017 and December 2018. EXPOSURE Continuous PPI use during the 2015 to 2016 AGE winter epidemic. MAIN OUTCOMES AND MEASURES The occurrence of at least 1 AGE episode during the 2015 to 2016 AGE winter epidemic was the main outcome. Episodes of AGE were identified using a previously validated algorithm based on drug dispensing data. Relative risks of AGE were estimated using a multivariable log-binomial model adjusted for age, sex, and treatments for chronic conditions. RESULTS There were 233 596 patients receiving PPI therapy (median [interquartile range] age, 71 [62-81] years; 55.8% female) and 626 887 matched patients not receiving PPI therapy (median [interquartile range] age, 70 [61-80] years; 56.3% female) included in the analyses. At least 1 AGE epidemic episode was identified in 3131 patients (1.3%) receiving PPI therapy and in 4327 patients (0.7%) not receiving PPI therapy. The adjusted relative risk of AGE for those receiving PPI therapy was 1.81 (95% CI, 1.72-1.90) for all ages considered, 1.66 (95% CI, 1.54-1.80) among those aged 45 to 64 years, 2.19 (95% CI, 1.98-2.42) among those aged 65 to 74 years, and 1.98 (95% CI, 1.82-2.15) among those aged 75 years and older. CONCLUSIONS AND RELEVANCE Continuous PPI therapy was associated with an increased risk of developing AGE during periods of highest circulation of enteric viruses. These findings support the hypothesis that PPI use is associated with an increased risk of enteric viral infections.

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Association of Proton Pump Inhibitors With Hospitalization Risk in Children With Oropharyngeal Dysphagia

Duncan

Mitchell

Larson

et al. 2018

JAMA Otolaryngol Head Neck Surg

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IMPORTANCE Proton pump inhibitors (PPI) are commonly prescribed to children with oropharyngeal dysphagia and resultant aspiration based on the assumption that these patients are at greater risk for reflux-related lung disease. There is little data to support this approach and the potential risk for increased infections in children treated with PPI may outweigh any potential benefit. OBJECTIVE The aim of this study was to determine if there is an association between hospitalization risk in pediatric patients with oropharyngeal dysphagia and treatment with PPI. DESIGN, SETTING, AND PARTICIPANTS We performed a retrospective cohort study to compare the frequency and length of hospitalizations for children who had abnormal results on videofluoroscopic swallow studies that were performed between January 1, 2015, and December 31, 2015, and who were or were not treated with PPI, with follow-up through December 31, 2016. Records were reviewed for children who presented for care at Boston Children's Hospital, a tertiary referral center. Participants included 293 children 2 years and younger with evidence of aspiration or penetration on videofluoroscopic swallow study. EXPOSURES Groups were compared based on their exposure to PPI treatment. MAIN OUTCOMES AND MEASURES The primary outcomes were hospital admission rate and hospital admission nights and these were measured as incident rates. Multivariable analyses were performed to determine predictors of hospitalization risk after adjusting for comorbidities. Kaplan-Meier curves were created to determine the association of PPI prescribing with time until first hospitalization. RESULTS A total of 293 patients with a mean (SD) age of 8.8 (0.4) months and a mean (SD) follow-up time of 18.15 (0.20) months were included in the analysis. Patients treated with PPI had higher admission rates (Incidence rate ratio [IRR], 1.77; 95% CI, 1.16-2.68) and admission nights (IRR, 2.51; 95% CI, 1.36-4.62) even after adjustment for comorbidities. Patients with enteral tubes who were prescribed PPIs were at the highest risk for admission (hazard ratio [HR], 2.31; 95% CI, 1.24-4.31). CONCLUSIONS AND RELEVANCE Children with aspiration who are treated with PPI have increased risk of hospitalization compared with untreated patients. These results support growing concern about the risks of PPI use in children.

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Proton Pump Inhibitors Alter Specific Taxa in the Human Gastrointestinal Microbiome: A Crossover Trial

Cited by 263 publications

References 32 publications

The influence of proton pump inhibitors and other commonly used medication on the gut microbiota

The influence of proton pump inhibitors and other commonly used medication on the gut microbiota

Association Between Acute Gastroenteritis and Continuous Use of Proton Pump Inhibitors During Winter Periods of Highest Circulation of Enteric Viruses

Association of Proton Pump Inhibitors With Hospitalization Risk in Children With Oropharyngeal Dysphagia

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