Compared to histamine-2 receptor antagonist, proton pump inhibitor induces stronger oral-to-gut microbial transmission and gut microbiome alterations: a randomised controlled trial

Abstract

ObjectiveWe aim to compare the effects of proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) on the gut microbiota through longitudinal analysis.DesignHealthy volunteers were randomly assigned to receive either PPI (n=23) or H2RA (n=26) daily for seven consecutive days. We collected oral (saliva) and faecal samples before and after the intervention for metagenomic next-generation sequencing. We analysed intervention-induced alterations in the oral and gut microbiome including microbial abundance and growth rates, oral-to-gut transmissions, and compared differences between the PPI and H2RA groups.ResultsBoth interventions disrupted the gut microbiota, with PPIs demonstrating more pronounced effects. PPI usage led to a significantly higher extent of oral-to-gut transmission and promoted the growth of specific oral microbes in the gut. This led to a significant increase in both the number and total abundance of oral species present in the gut, including the identification of known disease-associated species likeFusobacterium nucleatumandStreptococcus anginosus. Overall, gut microbiome-based machine learning classifiers could accurately distinguish PPI from non-PPI users, achieving an area under the receiver operating characteristic curve (AUROC) of 0.924, in contrast to an AUROC of 0.509 for H2RA versus non-H2RA users.ConclusionOur study provides evidence that PPIs have a greater impact on the gut microbiome and oral-to-gut transmission than H2RAs, shedding light on the mechanism underlying the higher risk of certain diseases associated with prolonged PPI use.Trial registration numberChiCTR2300072310.

Alterations in gut microbiota and bile acids by proton‐pump inhibitor use and possible mediating effects on elevated glucose levels and insulin resistance

“…A number of interventional and observational studies have suggested that long‐term PPI use is associated with alterations in the abundance and diversity of various microbial species 16,29–32 . Consistent with our findings, a study based on 1827 healthy twins showed that PPI use was negatively associated with 22 OTUs from the Firmicutes phylum and positively associated with 20 OTUs from the Bacteroidales order.…”

“…This was in line with our findings that PPI users had a lower abundance of Firmicutes and a higher abundance of the Bacteroidetes phylum 29 . PPI use could induce oral bacteria to colonize the gut by reducing the acidity of the stomach 16,32 . A recent randomized clinical trial (RCT) indicated that PPIs could cause a higher extent of oral‐to‐gut transmission and promote the growth of certain oral species in the gut compared to H2 receptor antagonists (H2RAs), a less potent acid suppressor, and subsequently have a more pronounced effect on disrupting the gut microbiota 32 .…”

“…PPI use could induce oral bacteria to colonize the gut by reducing the acidity of the stomach 16,32 . A recent randomized clinical trial (RCT) indicated that PPIs could cause a higher extent of oral‐to‐gut transmission and promote the growth of certain oral species in the gut compared to H2 receptor antagonists (H2RAs), a less potent acid suppressor, and subsequently have a more pronounced effect on disrupting the gut microbiota 32 . Another recent RCT in China indicated that PPIs altered the gut microbiota by increasing gastrointestinal pH and subsequently inducing the translocation of oral bacteria to the gut, and mouthwash could weaken these changes 33 .…”

Explainable machine learning model for identifying key gut microbes and metabolites biomarkers associated with myasthenia gravis

“…The inclusion criteria were (1) having MG signs and symptoms, such as muscle weakness and fatigue, and symptom fluctuation; (2) being seropositive for autoantibodies; (3) abnormal repetitive nerve stimulation or single-fiber electromyography; and (4) undergoing follow-up for ≥ 6 months from baseline. The exclusion criteria were (1) receiving aggressive immunomodulation therapy, including plasmapheresis, intravenous immunoglobulin, or rituximab, in the previous year or during the study inclusion period; (2) receiving antibiotics, probiotics in the previous 6 months; (3) having digestive disorders necessitating the use of a proton pump inhibitor or histamine-2 receptor antagonist, and disorders that related with change fecal microenvironments, such as inflammatory bowel disease in the previous year [20] , [21] ; or (4) requiring no immunosuppressant dose adjustment in the past one year. This study was approved by the Research Ethics Committee of Fu-Jen Catholic University Hospital (approval number: FJUH109042).…”

Stomach microbiota in gastric cancer development and clinical implications

“…The use of acid suppressants, for example, proton pump inhibitors, elevates the gastric pH to over 6, which encourages the growth of gastric microbes. 14 Additionally, throughout the Correa's cascade of gastric carcinogenesis which is mainly triggered by H. pylori, increased infiltration of inflammatory cells and displacement of normal glandular tissue by metaplastic glands can eventually lead to the occurrence of neoplastic tissues in the stomach. 15 Thus, gastric pH increases while pepsin level decreases, enabling the expansion and alterations of microorganisms in the stomach.…”