The human gut microbiome and asprin-induced gut injury

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K08366
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Tokyo Medical University
• Principal Investigator: Takashi Kawai 東京医科大学, 医学部, 主任教授 (40266490)
• Co-Investigator(Kenkyū-buntansha): 永田 尚義 東京医科大学, 医学部, 准教授 (10562788)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 腸内細菌 / 腸内真菌 / 機能代謝遺伝子 / メタゲノム解析 / ショットガンメタゲノム / 大規模コホート研究 / 多剤併用

Outline of Final Research Achievements

We conducted shotgun metagenomic sequencing of a total of 5,200 fecal samples.
We found that the microbial diversity (β-diversity) between aspirin users and non-users differed significantly, but not α-diversity. In contrast, PPIs showed significant and marked differences in both α-diversity and β-diversity, and increased α-diversity. We revealed aspirin was found to decrease Blautia spp. and increase Strepotococcus and Lactobacillus spp. Warfarin, DOAC, thienopyridines, and aspirin showed different bacterial signatures. In contrast, bacterial changes, such as streptococcus and Lactobacillus in PPI were consistent with the aspirin, whereas the PPI increased abundances oral-derived bacterial and decreases in butyrate-producers.
Importantly, an additive effect of aspirin and PPI on gut microbiota compared to the single-drug use. Furthermore, mycobiome analysis showed no significant changes in aspirin users, while PPI users showed changes in some fungal species.

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Academic Significance and Societal Importance of the Research Achievements

薬剤の中でも世界的に頻度の高いアスピリンと胃酸分泌抑制薬（PPI）の腸内環境への影響を見出した。PPIでは著明な口腔内細菌の増加と酪酸産生菌の低下を認めた。また、アスピリンとの併用により腸内における口腔内細菌の相加効果があることが分かった。この2剤は血栓塞栓症で併用することが多い薬剤であり、継続的に使用することで腸内環境の負の影響から新たな疾患発症のリスクにもなる可能性が示唆された。今後、同定した腸内細菌種の変化が実際に粘膜障害を起こす機序を動物実験などの基礎研究で明らかにする必要がある。