Proton Pump Inhibitors and Oral–Gut Microbiota: From Mechanism to Clinical Significance
Abstract
:1. Introduction
2. Impact of PPIs on Oral and Gut Microbiota
2.1. PPIs and Oral Microbiota
Study | Study Design | Patient Characteristic | Confounders | Sample | Sequencing Methods | Alpha Diversity | Beta Diversity | Taxonomic Changes |
---|---|---|---|---|---|---|---|---|
Tsuda et al. (2015) [21] | Cross-sectional study | Total patients (n = 45), including 12 functional dyspepsia and six GERD patients taking a PPI for more than 2 years, 27 of 45 healthy volunteers. | Matching for age | Saliva | Barcoded 454 pyrosequencing, 16S rDNA, V1-V2 | OTU number (ns) | Unweighted UniFrac distance (sig.) PCoA analysis (ns) | ns |
Rosen et al. (2015) [24] | Cross-sectional study | Children undergoing bronchoscopy and gastrointestinal endoscopy for chronic cough (n = 116), 59 were receiving a PPI dose within 24 h of endoscopy. | - | Oropharyngeal swabs | Illumina Miseq sequencing, 16S rDNA, - | Shannon index (ns) | - | Increased prevalence: Butyrivibrio Increased abundance: Allobaculum, Bifidobacterium, Cloacibacterium, Janthinobacterium, Ralstonia, Rhodobacter, Rhodoferax, Streptococcus, Yersinia, and Zoogloea. |
Mishiro et al. (2018) [22] | Prospective self-controlled trial | Healthy adults (n = 10) before and after four weeks of 20 mg esomeprazole once daily. | - | Saliva, periodontal pocket fluid | Illumina Miseq sequencing, 16S rDNA, V3-V4 | Chao1 (ns) Shannon index (sig. in saliva) | UniFrac distance (ns) PCoA analysis (sig. in saliva) | Increase: Fusobacterium and Leptotrichia in periodontal pocket fluid Decrease: Neisseria, Veillonella, and Haemophilus in saliva |
Kawar et al. (2021) [23] | Cross-sectional study | Total patients (n = 128), including 20 patients with GERD who used PPIs, and 16 who had GERD but did not use medication, 102 negative control subjects. | Matching for age, periodontal status, and edentualism. | Saliva | Illumina Miseq sequencing, 16S rDNA, V1-V3 | Chao1 (ns) Shannon index (ns) | PCoA analysis (ns) | Decrease: Prevotella melaninogenica, Prevotella pallens, Solobacterium moorei and Leptotrichia in the GERD patients not using PPIs compared to negative controls. |
2.2. PPIs and Gut Microbiota
3. Influence of Oral–Gut Translocation on PPI-Induced Gut Microbiota Alteration
4. Oral–Gut Microbiota and PPI-Related Digestive System Complications
4.1. Cirrhosis and Related Complications
4.2. Gastric Cancer
4.3. Esophageal Cancer
4.4. Colorectal Cancer
4.5. Clostridium Difficile Infection and Other Enteric Infections
4.6. Inflammatory Bowel Disease
4.7. Lower Gastrointestinal Bleeding
4.8. Biliary Tract Diseases
5. Conclusions and Future Directions
Author Contributions
Funding
Conflicts of Interest
References
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Study | Study Design | Patient Characteristic | Sample | Methods | Translocated Oral Microbes in the Gut | Major Findings | |
---|---|---|---|---|---|---|---|
Genus | Species | ||||||
Imhann et al. (2016) [11] | Cross-sectional study | A total of 1815 individuals (211 PPI users) in three independent cohorts from the Netherlands: LifeLines-DEEP study, IBD cohort, IBS case-control study. | Oral cavity mucus samples and Feces | Illumina Miseq sequencing, 16S rDNA, V4 | Rothia, Streptococcus, Actinomyces, Alloscardovia, Lactobacillus, Oribacterium, Granulicatella, Scardovia, Staphylococcus, Atopobium, Corynebacterium | Rothia mucilaginosa, Rothia dentocariosa, Lactobacillus salivarius, Streptococcus sobrinus, Streptococcus anginosus, Staphylococcus aureus, Staphylococcus epidermidis, Lactobacillus reuteri, Lactobacillus vaginalis, Lactobacillus delbrueckii, Streptococcus infantis, Atopobium rimae, Staphylococcus haemolyticus. | Multiple oral bacteria were over represented in the fecal microbiome of PPI users. |
Jackson et al. (2016) [12] | Cross-sectional study | 1827 healthy twins from the TwinsUK cohort. | Feces | Illumina Miseq sequencing, 16S rDNA, V4 | Rothia, Streptococcus, Scardovia, Granulicatella, Oribacterium, Lactobacillus, Corynebacterium | Rothia mucilaginosa, Streptococcus anginosus | PPI use was associated with a significant increase in the abundance of oral and upper gastrointestinal tract commensals in gut commensals. |
Otsuka et al. (2016) [34] | Prospective interventional trial | Helicobacter pylori IgG-negative healthy individuals (n = 20) taking four-week of 30 mg lansoprazole (n = 11) or 20 mg vonoprazan daily (n = 9). | Feces | Illumina Miseq sequencing, 16S rDNA, - | PPI group: Streptococcus, Carnobacterium, Oribacterium Vonoprazan group: Actinomyces, Rothia, Granulicatella, Streptococcus | - | Oral microbiome is more abundant in the gut microbiome after vonoprazan treatment as compared with lansoprazole treatment. |
Xiao et al. (2024) [17] | Prospective self-controlled trial | Healthy adults (n = 16) taking 7-day course of 40 mg esomeprazole once daily. | Saliva and Feces | Illumina Miseq sequencing, 16S rDNA, V3-V4 | Streptococcus, Gemella | Streptococcus anginosus, Streptococcus parasanguinis clade 411, Streptococcus salivarius, Streptococcus vestibularis, Streptococcus mitis, Streptococcus sp. HMT 061, Streptococcus oralis subsp. dentisani clade 398, Streptococcus oralis subsp. dentisani clade 058, Lactococcus lactis | PPI administration increased Streptococcus abundance in gut microbiota, and the increased species of Streptococcus were found to be from the oral site or oral/nasal sites, in which Streptococcus anginosus was identified as the significantly changed species. |
Zhu et al. (2024) [33] | Prospective randomized controlled trial | Healthy adults (n = 49) before and after 7-day course of 20 mg omeprazole (n = 23) or 20 mg famotidine daily (n = 26). | Saliva and Feces | Shotgun metagenomic sequencing | PPI group: Streptococcus, Rothia H2RA group: Streptococcus | PPI group: Actinomyces bouchesdurhonensis, Actinomyces oris, Actinomyces SGB17168, Actinomyces sp ICM58, Actinomyces sp S6 Spd3, Trueperella pyogenes, Rothia mucilaginosa, Isoptericola variabilis, Gemella sanguinis, Abiotrophia defective, Streptococcus constellatus, Streptococcus cristatus, Streptococcus mitis, Streptococcus sanguinis, Streptococcus sp 263 SSPC, Mogibacterium diversum, Solobacterium SGB6833, Megasphaera micronuciformis, Parvimonas micra, Fusobacterium nucleatum, Fusobacterium pseudoperiodonticum, Haemophilus sputorum H2RA group: Actinomyces, Bouchesdurhonensis, Rothia mucilaginosa, Isoptericola variabilis, Gemella sanguinis, Solobacterium SGB6833 | PPI usage led to a significantly higher extent of oral-to-gut transmission and promoted the growth of specific oral microbes in the gut than H2RA usage. |
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Zhang, X.; Li, Q.; Xia, S.; He, Y.; Liu, Y.; Yang, J.; Xiao, X. Proton Pump Inhibitors and Oral–Gut Microbiota: From Mechanism to Clinical Significance. Biomedicines 2024, 12, 2271. https://doi.org/10.3390/biomedicines12102271
Zhang X, Li Q, Xia S, He Y, Liu Y, Yang J, Xiao X. Proton Pump Inhibitors and Oral–Gut Microbiota: From Mechanism to Clinical Significance. Biomedicines. 2024; 12(10):2271. https://doi.org/10.3390/biomedicines12102271
Chicago/Turabian StyleZhang, Xian, Qing Li, Siyuan Xia, Yan He, Yuqiang Liu, Jinlin Yang, and Xue Xiao. 2024. "Proton Pump Inhibitors and Oral–Gut Microbiota: From Mechanism to Clinical Significance" Biomedicines 12, no. 10: 2271. https://doi.org/10.3390/biomedicines12102271
APA StyleZhang, X., Li, Q., Xia, S., He, Y., Liu, Y., Yang, J., & Xiao, X. (2024). Proton Pump Inhibitors and Oral–Gut Microbiota: From Mechanism to Clinical Significance. Biomedicines, 12(10), 2271. https://doi.org/10.3390/biomedicines12102271