Does Long-Term Proton Pump Inhibitor Therapy Affect the Health of Gut Microbiota?

Lee, Chansu; Hong, Sung Noh

doi:10.5009/gnl16438

Cited by 4 publications

(3 citation statements)

References 10 publications

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“…Furthermore, the results suggest that PPI-associated increase of some bacterial populations may lead to infections and diseases or increase susceptibility for other bacterial infections (like Veilonella) or promote a carcinogenic effect (like Veilonella) . Previous studies have highlighted that PPI intake is associated with decreased bacterial richness 16 , 18 , 56 , 57 , increased risk of enteric and other infections (e.g. caused by Salmonella, Clostridium difficile , Shigella, Listeria ) 17 , 58 , increase in the abundance of oral and upper GI tract commensals and potential pathogenic bacteria (e.g.…”

Section: Resultsmentioning

confidence: 99%

Nonlinear machine learning pattern recognition and bacteria-metabolite multilayer network analysis of perturbed gastric microbiome

Durán¹,

Ciucci²,

Palladini

et al. 2021

Nat Commun

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The stomach is inhabited by diverse microbial communities, co-existing in a dynamic balance. Long-term use of drugs such as proton pump inhibitors (PPIs), or bacterial infection such as Helicobacter pylori, cause significant microbial alterations. Yet, studies revealing how the commensal bacteria re-organize, due to these perturbations of the gastric environment, are in early phase and rely principally on linear techniques for multivariate analysis. Here we disclose the importance of complementing linear dimensionality reduction techniques with nonlinear ones to unveil hidden patterns that remain unseen by linear embedding. Then, we prove the advantages to complete multivariate pattern analysis with differential network analysis, to reveal mechanisms of bacterial network re-organizations which emerge from perturbations induced by a medical treatment (PPIs) or an infectious state (H. pylori). Finally, we show how to build bacteria-metabolite multilayer networks that can deepen our understanding of the metabolite pathways significantly associated to the perturbed microbial communities.

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Section: Resultsmentioning

confidence: 99%

Nonlinear machine learning pattern recognition and bacteria-metabolite multilayer network analysis of perturbed gastric microbiome

Durán¹,

Ciucci²,

Palladini

et al. 2021

Nat Commun

View full text Add to dashboard Cite

show abstract

“…Furthermore, the results suggest that PPI-associated increas of some bacterial populations may lead to infections and diseases or increase susceptibility for other bacterial infections (like Veilonella) or promote a carcinogenic effect (like Veilonella). Previous studies have highlighted that PPI intake is associated with decreased bacterial richness 16,18,89,90 , increased risk of enteric and other infections (e.g. caused by Salmonella, Clostridium difficile , Shigella, Listeria ) 17,91 , increase in the abundance of oral and upper GI tract commensals and potential pathogenic bacteria (e.g.…”

Section: Resultsmentioning

confidence: 99%

Machine learning pattern recognition and differential network analysis of gastric microbiome in the presence of proton pump inhibitor treatment or Helicobacter pylori infection

Ciucci

Durán

Palladini

et al. 2020

Preprint

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40Although long thought to be a sterile and inhospitable environment, the stomach is inhabited 41 by diverse microbial communities, co-existing in a dynamic balance. Long-term use of orally 42 administered drugs such as Proton Pump Inhibitors (PPIs), or bacterial infection such as 43 Helicobacter pylori, cause significant microbial alterations. Yet, studies revealing how the 44 commensal bacteria re-organize, due to these perturbations of the gastric environment, are in 45 the early phase. They mainly focus on the most prevalent taxa and rely on linear techniques for 46 multivariate analysis. 47Here we disclose the importance of complementing linear dimensionality reduction techniques 48 such as Principal Component Analysis and Multidimensional Scaling with nonlinear 49 approaches derived from the physics of complex systems. Then, we show the importance to 50 complete multivariate pattern analysis with differential network analysis, to reveal mechanisms 51 of re-organizations which emerge from combinatorial microbial variations induced by a 52 medical treatment (PPIs) or an infectious state (H. pylori). 53 Keywords 54 Proton Pump Inhibitors -Dyspepsia -Helicobacter pylori -Gastric microbiota -Linear and 55 nonlinear unsupervised methods -Mininum Curvilinear Embedding -Nonlinearity -PC-corr 56 network -16S rRNA 57 58 3 Introduction 59The gastric environment with its microbiota is the active gate that regulates access to the whole 60 gastrointestinal tract, and therefore it has a remarkable impact on the correct functionality of 61 the entire human organism. Recent studies have revealed that many orally administered drugs 62 can perturb the elegant balance of the gastric flora 1,2 . However, not all of them cause permanent 63 adverse effects and particular attention should be addressed to drugs that are frequently 64 prescribed and administered for long periods. They can cause permanent unbalance of the 65 gastric microbiota that might generate adverse side effects for the patient's health. Since the 66 introduction of proton pump inhibitors (PPIs) into clinical practice more than 25 years ago, PPIs 67 have become the mainstay in the treatment of gastric-acid-related diseases 3 . PPIs are potent 68 agents that block acid secretion by gastric parietal cells by binding covalently to and inhibiting 69 the hydrogen/potassium (H + /K + )-ATPases (or proton pumps), and additionally they can bind 70 non-gastric H + /K + -ATPases, both on human cells and on bacteria and fungi, such as 71 Helicobacter pylori (H. pylori) 4-6 . 72 PPIs are drugs of first choice for peptic ulcers (PU) and their complications (e.g. bleeding), 73 gastroesophageal reflux disease (GERD), nonsteroidal anti-inflammatory drug (NSAID)-74 induced gastrointestinal (GI) lesions, Zollinger-Ellison syndrome and dyspepsia 3,7,8 . In 75 particular, dyspepsia is a common clinical problem characterized by symptoms (e.g. epigastric 76 pain, burning, postprandial fullness, or early satiation) originating from the gastroduodenal 77 region 9 . The potent gastri...

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“…However, due to ethical reasons, this approach is not feasible in humans. [116] In rat models, long-term use of lansoprazole (50 weeks) was associated with significant shift in terminal ileum bacterial composition: a predominance of Proteobacteria (93.9%, mainly Escherichia and Pasteurella genera) in the controls and the abundance of Firmicutes (66.9%, mainly Clostridium and Lactobacillus genera) in the treatment group. [117]…”

Section: Intestinal Microbiomementioning

confidence: 99%

The Gastric and Intestinal Microbiome: Role of Proton Pump Inhibitors

Minalyan

Gabrielyan

Scott

et al. 2017

Curr Gastroenterol Rep

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Purpose of review The discovery of Helicobacter pylori and other organisms colonizing the stomach and the intestines has shed some light on the importance of microbiome in maintaining overall health and developing pathological conditions when alterations in biodiversity are present. The gastric acidity plays a crucial role in filtering out bacteria and preventing development of enteric infections. In this article, we discuss the physiology of gastric acid secretion and bacterial contribution to the composition of gastric and intestinal barriers and review the current literature on the role of proton pump inhibitors (PPIs) in the microbial biodiversity of the gastrointestinal tract. Recent findings Culture-independent techniques, such as 16S rRNA sequencing, have revolutionized our understanding of the microbial biodiversity in the gastrointestinal tract. Luminal and mucosa-associated microbial populations are not identical. Streptococcus is overrepresented in the biopsies of patients with antral gastritis and may also be responsible for the development of peptic ulcer disease. The use of PPIs favors relative streptococcal abundance irrespective of H. pylori status and may explain the persistence of dyspeptic symptoms in patients on PPI therapy. Increased risk of enteric infections has also been seen in patients taking PPIs. The overuse of PPIs leads to significant shift of the gastrointestinal microbiome towards a less healthy state. Summary With the advent of PPIs, many studies have demonstrated the significant changes in the microbial composition of both gastric and intestinal microbiota. Although they are considered relatively safe over-the-counter medications, PPIs in many cases are over- and even inappropriately used. Future studies assessing the safety of PPIs and their role in the development of microbiome changes should be encouraged.

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Does Long-Term Proton Pump Inhibitor Therapy Affect the Health of Gut Microbiota?

Cited by 4 publications

References 10 publications

Nonlinear machine learning pattern recognition and bacteria-metabolite multilayer network analysis of perturbed gastric microbiome

Nonlinear machine learning pattern recognition and bacteria-metabolite multilayer network analysis of perturbed gastric microbiome

Machine learning pattern recognition and differential network analysis of gastric microbiome in the presence of proton pump inhibitor treatment or Helicobacter pylori infection

The Gastric and Intestinal Microbiome: Role of Proton Pump Inhibitors

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