Influence of proton pump inhibitor or rebamipide use on gut microbiota of rheumatoid arthritis patients

Abstract Objective Patients with rheumatoid arthritis (RA) commonly use gastrointestinal (GI) protective drugs for treatment and prevention of peptic ulcer disease. However, how these drugs affect gut microbiota is unknown in RA patients. The objective of this study was to examine the gut microbiota of RA patients according to their use of GI protective drugs, such as proton pump inhibitors (PPIs), H2-receptor antagonists, and rebamipide. Methods Fecal samples were obtained from 15 healthy controls (HCs) and 32 RA patients who were receiving PPI, H2-receptor antagonist, or rebamipide. Bacterial DNA was extracted from the fecal samples and 16S rRNA sequencing was performed. Microbial composition and function were analyzed using QIIME and PICRUSt. Results RA patients showed reduced diversity and altered composition of the gut microbiota compared with HCs. Gut microbiota of RA patients receiving acid-suppressing drugs, particularly PPI, was distinct from that of RA patients receiving rebamipide (PPI versus rebamipide, p=0.005). Streptococcus was enriched in RA patients receiving PPI, whereas Clostridium bolteae was enriched in RA patients receiving rebamipide. Gut microbiota of PPI-users was highly expressing the microbial functional pathway involved in virulence factors production. This featured microbial function was positively correlated with the relative abundance of Streptococcus, the differentially abundant taxa of PPI-users. Conclusions Gut microbiota of RA patients receiving PPI was distinguished from those receiving rebamipide. Enriched virulent function in gut microbiota of PPI-users suggests that PPIs should not be overprescribed in RA patients.