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Proton pump inhibitors affect the gut microbiome.

ABSTRACT: BACKGROUND AND AIMS:Proton pump inhibitors (PPIs) are among the top 10 most widely used drugs in the world. PPI use has been associated with an increased risk of enteric infections, most notably Clostridium difficile. The gut microbiome plays an important role in enteric infections, by resisting or promoting colonisation by pathogens. In this study, we investigated the influence of PPI use on the gut microbiome. METHODS:The gut microbiome composition of 1815 individuals, spanning three cohorts, was assessed by tag sequencing of the 16S rRNA gene. The difference in microbiota composition in PPI users versus non-users was analysed separately in each cohort, followed by a meta-analysis. RESULTS:211 of the participants were using PPIs at the moment of stool sampling. PPI use is associated with a significant decrease in Shannon's diversity and with changes in 20% of the bacterial taxa (false discovery rate <0.05). Multiple oral bacteria were over-represented in the faecal microbiome of PPI-users, including the genus Rothia (p=9.8×10(-38)). In PPI users we observed a significant increase in bacteria: genera Enterococcus, Streptococcus, Staphylococcus and the potentially pathogenic species Escherichia coli. CONCLUSIONS:The differences between PPI users and non-users observed in this study are consistently associated with changes towards a less healthy gut microbiome. These differences are in line with known changes that predispose to C. difficile infections and can potentially explain the increased risk of enteric infections in PPI users. On a population level, the effects of PPI are more prominent than the effects of antibiotics or other commonly used drugs.

SUBMITTER: Imhann F

PROVIDER: S-EPMC4853569 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Proton pump inhibitors affect the gut microbiome.

Imhann Floris F Bonder Marc Jan MJ Vich Vila Arnau A Fu Jingyuan J Mujagic Zlatan Z Vork Lisa L Tigchelaar Ettje F EF Jankipersadsing Soesma A SA Cenit Maria Carmen MC Harmsen Hermie J M HJ Dijkstra Gerard G Franke Lude L Xavier Ramnik J RJ Jonkers Daisy D Wijmenga Cisca C Weersma Rinse K RK Zhernakova Alexandra A

Gut 20151209 5

<h4>Background and aims</h4>Proton pump inhibitors (PPIs) are among the top 10 most widely used drugs in the world. PPI use has been associated with an increased risk of enteric infections, most notably Clostridium difficile. The gut microbiome plays an important role in enteric infections, by resisting or promoting colonisation by pathogens. In this study, we investigated the influence of PPI use on the gut microbiome.<h4>Methods</h4>The gut microbiome composition of 1815 individuals, spanning ...[more]

PMID: 26657899

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Project description:BackgroundCurrently, few studies focus on the association between gut microbiota and systemic lupus erythematosus (SLE), and much less studies consider the effect of drug usage. Proton pump inhibitors (PPIs) are commonly used to treat drug-related gastrointestinal damage in SLE patients. Therefore, the purpose of this study is to examine the gut microbiota of SLE patients using PPIs.MethodsFecal samples from 20 SLE patients with PPIs (P-SLE), 20 SLE patients without PPIs (NP-SLE) and 17 healthy controls (HCs) were obtained. The structure of the bacterial community in the fecal samples was analyzed by 16S rRNA gene sequencing. Redundancy analysis (RDA) was performed to observe the relationship between clinical variables and microbiome composition in P-SLE and NP-SLE patients. Based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, functional capabilities of microbiota were estimated. Network analysis was performed to analyze the association of metabolic pathway alterations with altered gut microbiota in P-SLE and NP-SLE patients.ResultsP-SLE patients exhibited increased alpha-diversity and an altered composition of the gut microbiota compared with NP-SLE patients. The alpha-diversity of NP-SLE patients was significantly lower than HCs but also of P-SLE patients, whose alpha-diversity had become similar to HCs. Compared with NP-SLE patients, the relative abundances of Lactobacillus, Roseburia, Oxalobacter, and Desulfovibrio were increased, while those of Veillonella, Escherichia, Morganella, Pseudomonas and Stenotrophomonas were decreased in P-SLE patients. RDA indicated that PPI use was the only significant exploratory variable for the microbiome composition when comparing SLE patients. KEGG analysis showed that 16 metabolic pathways were significantly different between NP-SLE and P-SLE patients. These metabolic pathways were mainly associated with changes in Escherichia, Roseburia, Stenotrophomonas, Morganella and Alipipes as determined by the network analysis.ConclusionsPPI use is associated with an improved microbiome composition of SLE patients as it 1) increases alpha-diversity levels back to normal, 2) increases the abundance of various (beneficial) commensals, and 3) decreases the abundance of certain opportunistic pathogenic genera such as Escherichia. Validation studies with higher patient numbers are however recommended to explore these patterns in more detail.

Dataset Information

Proton pump inhibitors affect the gut microbiome.

Publications

Proton pump inhibitors affect the gut microbiome.

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