The Effect of Proton-Pomp Inhibitors on the Gut Microbiota by Metagnome Approach

2022 Fiscal Year Final Research Report

• Project/Area Number: 17K09365
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Tokyo Medical University (2020, 2022); National Center for Global Health and Medicine (2017-2018)
• Principal Investigator: Nagata Naoyoshi 東京医科大学, 医学部, 准教授 (10562788)
• Project Period (FY): 2017-04-01 – 2023-03-31
• Keywords: 腸内細菌 / 口腔内細菌 / 機能代謝遺伝子 / KEGG / マイクロバイオーム / 薬剤使用 / 多剤併用

Outline of Final Research Achievements

Relationships between gut microbiota and PPIs, potassium competitive acid blockers (PCABs), and histamine H2 receptor antagonist (H2RA) use were examined. We found microbial signatures of PPI and PCAB were substantially overlapped, but not H2RA. Moreover, the proportion of multidrug-resistant bacteria (ESKAPE pathogens), which cause opportunistic infections, increased in the gut with PPI use, but not H2RA. A comprehensive microbial functional analysis identified more than 10,000 functional genes, among which PPI and PCAB were both characterized by findings of an elevated gene cluster related to amino acid metabolism, carbohydrate metabolism, and vitamin metabolism, but not H2RA. Administration of PPI showed an increase in bacteria of oral origin and pathogens after PPI use, but these species decreased with PPI discontinuation.

Free Research Field

マイクロバイオーム

Academic Significance and Societal Importance of the Research Achievements

薬剤の中でも消化器系の薬剤、とくにPPIやPCABなど薬剤が最も影響度が強い。PPIやPCAB使用に伴う腸内細菌叢への影響は、ほか薬剤併用による相加的効果、口腔内細菌の流入、細菌が担う食物代謝機能の更新、日和見菌増加などの広範囲に認められた。胃酸分泌抑制薬による腸内環境への負の影響を示唆するものであり、適正な薬剤投与の適応や投与期間を見直す意義が強調された。