Proton Pump Inhibitor-Induced Gut Dysbiosis Increases Mortality Rates for Patients with Clostridioides difficile Infection

Lin, Cheng‐Yu; Cheng, Hao‐Tsai; Kuo, Chia‐Jung; Lee, Yun‐Shien; Sung, Chang‐Mu; Keidan, Micah; Rao, Krishna; Kao, John Y.; Hsieh, Sen‐Yung

doi:10.1128/spectrum.00486-22

Cited by 20 publications

(6 citation statements)

References 48 publications

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“…play a key role in regulating human microbiome health and are mostly associated with oral infections. In fact, a newly published study found that the relative abundance of Prevotella copri and Ruminococcus gnavus is inversely correlated with the duration of PPI use in patients with CDI [ 54 ], which supports the discovery of the decrease in the abundance of Paraprevotella , Prevotella 2 , and Prevotella 9 belonging to the Prevotellaceae family in our results. The altered abundance of Prevotella caused by the use of PPIs might therefore worsen infection and be associated with some risk factors for inflammatory diseases.…”

Section: Discussionsupporting

confidence: 91%

Meta-analysis of the effects of proton pump inhibitors on the human gut microbiota

Zhang

et al. 2023

BMC Microbiol

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Mounting evidence has linked changes in human gut microbiota to proton pump inhibitor (PPI) use. Accordingly, multiple studies have analyzed the gut microbiomes of PPI users, but PPI–microbe interactions are still understudied. Here, we performed a meta-analysis of four studies with available 16S rRNA gene amplicon sequencing data to uncover the potential changes in human gut microbes among PPI users. Despite some differences, we found common features of the PPI-specific microbiota, including a decrease in the Shannon diversity index and the depletion of bacteria from the Ruminococcaceae and Lachnospiraceae families, which are crucial short-chain fatty acid-producers. Through training based on multiple studies, using a random forest classification model, we further verified the representativeness of the six screened gut microbial genera and 20 functional genes as PPI-related biomarkers, with AUC values of 0.748 and 0.879, respectively. Functional analysis of the PPI-associated 16S rRNA microbiome revealed enriched carbohydrate- and energy-associated genes, mostly encoding fructose-1,6-bisphosphatase and pyruvate dehydrogenase, among others. In this study, we have demonstrated alterations in bacterial abundance and functional metabolic potential related to PPI use, as a basis for future studies on PPI-induced adverse effects.

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Section: Discussionsupporting

confidence: 91%

Meta-analysis of the effects of proton pump inhibitors on the human gut microbiota

Zhang

et al. 2023

BMC Microbiol

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“…As dietary change is an external factor that alters the gut microbiota, an initial increase in diversity may have occurred in the high-dose group. In addition, increased diversity of the gut microbiota can positively affect host health by maintaining gut homeostasis ( 27 ), whereas decreased diversity is associated with various gastrointestinal, metabolic, and immune diseases, indicating dysbiosis of the gut microbiota ( 28 , 29 ). Thus, red ginseng dietary fiber may improve host health by increasing gut microbial diversity.…”

Section: Discussionmentioning

confidence: 99%

Red Ginseng Dietary Fiber Shows Prebiotic Potential by Modulating Gut Microbiota in Dogs

Song,

Lee,

et al. 2023

Microbiol Spectr

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“…Among these selected species, there are species that are known commensals such as Faecalibacterium prausnitzii and Bacteroides thetaiotaomicron 62 and species that are known to co-colonize with C. difficile such as Klebsiella pneumoniae , 63 and species that are reported to provide some protection against CDI such as Prevotella copri and Ruminococcus gnavus . 64 …”

Section: Discussionmentioning

confidence: 99%

Functional profile of host microbiome indicates Clostridioides difficile infection

Nzabarushimana

Tang

2022

Gut Microbes

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Clostridioides difficile infection (CDI) is a gastro-intestinal (GI) infection that illustrates how perturbations in symbiotic host–microbiome interactions render the GI tract vulnerable to the opportunistic pathogens. CDI also serves as an example of how such perturbations could be reversed via gut microbiota modulation mechanisms, especially fecal microbiota transplantation (FMT). However, microbiome-mediated diagnosis of CDI remains understudied. Here, we evaluated the diagnostic capabilities of the fecal microbiome on the prediction of CDI. We used the metagenomic sequencing data from ten previous studies, encompassing those acquired from CDI patients treated by FMT, CDI-negative patients presenting other intestinal health conditions, and healthy volunteers taking antibiotics. We designed a hybrid species/function profiling approach that determines the abundances of microbial species in the community contributing to its functional profile. These functionally informed taxonomic profiles were then used for classification of the microbial samples. We used logistic regression (LR) models using these features, which showed high prediction accuracy (with an average ), substantiating that the species/function composition of the gut microbiome has a robust diagnostic prediction of CDI. We further assessed the confounding impact of antibiotic therapy on CDI prediction and found that it is distinguishable from the CDI impact. Finally, we devised a log-odds score computed from the output of the LR models to quantify the likelihood of CDI in a gut microbiome sample and applied it to evaluating the effectiveness of FMT based on post-FMT microbiome samples. The results showed that the gut microbiome of patients exhibited a gradual but steady improvement after receiving successful FMT, indicating the restoration of the normal microbiome functions.

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Proton Pump Inhibitor-Induced Gut Dysbiosis Increases Mortality Rates for Patients with Clostridioides difficile Infection

Cited by 20 publications

References 48 publications

Meta-analysis of the effects of proton pump inhibitors on the human gut microbiota

Meta-analysis of the effects of proton pump inhibitors on the human gut microbiota

Red Ginseng Dietary Fiber Shows Prebiotic Potential by Modulating Gut Microbiota in Dogs

Functional profile of host microbiome indicates Clostridioides difficile infection

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