钾竞争性酸阻滞剂对接受经皮冠状动脉介入治疗患者肠道菌群的影响：一项随机初步研究。
完整摘要 · 中文译文
背景与目的：质子泵抑制剂（PPIs）常规用于接受经皮冠状动脉介入治疗（PCI）的患者，以预防与双联抗血小板治疗（DAPT）相关的胃肠道出血。然而，长期使用PPI与肠道菌群失调有关。替戈拉生（tegoprazan）是一种钾竞争性酸阻滞剂（P-CAB），可能对肠道微生物组产生不同的影响。本研究比较了替戈拉生和泮托拉唑对接受PCI的心绞痛患者肠道菌群组成的纵向影响。 方法：这项前瞻性、随机、对照的初步研究将38例患者按1：1：1随机分配至替戈拉生50 mg每日一次、泮托拉唑40 mg每日一次或不接受抑酸治疗，持续24周。5名参与者未提供基线粪便样本，9名参与者在第24周前退出研究。因此，最终分析纳入了24名提供配对基线和第24周粪便样本的参与者。粪便样本采用16S rRNA基因测序进行分析。 结果：各组均未发生药物相关不良事件或胃肠道出血。在整个队列（p = 0.003）和P-CAB组（p = 0.016）中，第24周观察到的扩增子序列变异（ASV）丰富度显著高于基线，而Shannon指数无显著变化。按患者ID限制置换的配对PERMANOVA分析显示，P-CAB组（R² = 0.070, p = 0.031）和PPI组（R² = 0.059, p = 0.008）基线与第24周之间的Bray-Curtisβ多样性存在显著差异，而无抑酸治疗组则无显著差异。 治疗组（R² = 0.021，p = 0.691）。在正式的交叉臂分析中，治疗组与访视的交互作用对Bray-Curtis β多样性不显著（R² = 0.021，伪F = 0.505，p = 0.270）。尽管观察到名义上的组内分类学变化，但在ANCOM-BC2中，没有治疗组与访视的交互作用通过Benjamini-Hochberg校正。 结论：替戈拉赞耐受性良好，在24周随访期间未出现药物相关不良事件或胃肠道出血。两个抑酸治疗组均表现出适度的纵向微生物组变化。分类学水平的结果属于探索性和假设生成性质，不应被解释为治疗特异性差异效应的确凿证据。需要更大规模、充分把握度的研究来证实这些观察结果。
完整摘要 · 英文原文
BACKGROUND AND AIM: Proton pump inhibitors (PPIs) are routinely used in patients undergoing percutaneous coronary intervention (PCI) to prevent gastrointestinal bleeding associated with dual-antiplatelet therapy (DAPT). However, long-term PPI use has been linked to gut microbiota dysbiosis. Tegoprazan, a potassium-competitive acid blocker (P-CAB), may exert distinct effects on the gut microbiome. This study compared the longitudinal effects of tegoprazan and pantoprazole on gut microbiota composition in patients with angina undergoing PCI. METHODS: This prospective, randomized, controlled pilot study randomized 38 patients 1:1:1 to tegoprazan 50 mg once daily, pantoprazole 40 mg once daily, or no acid-suppressive therapy for 24 weeks. Five participants did not provide baseline fecal samples, and nine discontinued participation before week 24. Thus, 24 participants with paired baseline and week-24 fecal samples were included in the final analysis. Fecal samples were analyzed using 16S rRNA gene sequencing. RESULTS: No drug-related adverse events or gastrointestinal bleeding occurred in any group. Observed amplicon sequence variant (ASV) richness was significantly higher at week 24 than at baseline in the overall cohort (p = 0.003) and P-CAB group (p = 0.016), whereas the Shannon index showed no significant changes. Paired PERMANOVA with permutations restricted by patient ID revealed significant differences in Bray-Curtis beta diversity between baseline and week 24 in the P-CAB group (R² = 0.070, p = 0.031) and PPI group (R² = 0.059, p = 0.008), but not in the no acid-suppressive therapy group (R² = 0.021, p = 0.691). In the formal cross-arm analysis, the treatment group-by-visit interaction was not significant for Bray-Curtis beta diversity (R² = 0.021, pseudo-F = 0.505, p = 0.270). Although nominal within-arm taxonomic changes were observed, no treatment group-by-visit interaction survived Benjamini-Hochberg correction in ANCOM-BC2. CONCLUSION: Tegoprazan was well tolerated, with no drug-related adverse events or gastrointestinal bleeding during the 24-week follow-up. Both acid-suppressive treatment groups showed modest longitudinal microbiome changes. The taxon-level findings were exploratory and hypothesis-generating and should not be interpreted as definitive evidence of treatment-specific differential effects. Larger, adequately powered studies are required to confirm these observations.