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Lung Allograft Microbiome Association with Gastroesophageal Reflux, Inflammation, and Allograft Dysfunction.
American Journal of Respiratory and Critical Care Medicine ( IF 24.7 ) Pub Date : 2022-12-15 , DOI: 10.1164/rccm.202110-2413oc
Pierre H H Schneeberger 1, 2, 3, 4 , Chen Yang Kevin Zhang 1, 2, 5 , Jessica Santilli 1, 2, 3 , Bo Chen 6 , Wei Xu 6 , Youngho Lee 1, 2, 3 , Zonelle Wijesinha 1, 2, 3 , Elaine Reguera-Nuñez 1, 2, 3 , Noelle Yee 1, 2, 3 , Musawir Ahmed 3, 5 , Kristen Boonstra 5 , Rayoun Ramendra 5 , Courtney W Frankel 7 , Scott M Palmer 7 , Jamie L Todd 7 , Tereza Martinu 1, 2, 3, 5 , Bryan Coburn 1, 2, 3
Affiliation  

Rationale: It remains unclear how gastroesophageal reflux disease (GERD) affects allograft microbial community composition in lung transplant recipients and its impact on lung allograft inflammation and function. Objectives: Our objective was to compare the allograft microbiota in lung transplant recipients with or without clinically diagnosed GERD in the first year after transplant and assess associations between GERD, allograft microbiota, inflammation, and acute and chronic lung allograft dysfunction (ALAD and CLAD). Methods: A total of 268 BAL samples were collected from 75 lung transplant recipients at a single transplant center every 3 months after transplant for 1 year. Ten transplant recipients from a separate transplant center provided samples before and after antireflux Nissen fundoplication surgery. Microbial community composition and density were measured using 16S ribosomal RNA gene sequencing and quantitative polymerase chain reaction, respectively, and inflammatory markers and bile acids were quantified. Measurements and Main Results: We observed a range of allograft community composition with three discernible types (labeled community state types [CSTs] 1-3). Transplant recipients with GERD were more likely to have CST1, characterized by high bacterial density and relative abundance of the oropharyngeal colonizing genera Prevotella and Veillonella. GERD was associated with more frequent transitions to CST1. CST1 was associated with lower inflammatory cytokine concentrations than pathogen-dominated CST3 across the range of microbial densities observed. Cox proportional hazard models revealed associations between CST3 and the development of ALAD/CLAD. Nissen fundoplication decreased bacterial load and proinflammatory cytokines. Conclusions: GERD was associated with a high bacterial density, Prevotella- and Veillonella-dominated CST1. CST3, but not CST1 or GERD, was associated with inflammation and early development of ALAD and CLAD. Nissen fundoplication was associated with a reduction in microbial density in BAL fluid samples, especially the CST1-specific genus, Prevotella.

中文翻译:

肺同种异体移植物微生物组与胃食管反流、炎症和同种异体移植物功能障碍的关联。

理由:目前尚不清楚胃食管反流病 (GERD) 如何影响肺移植受者的同种异体移植物微生物群落组成及其对肺同种异体移植物炎症和功能的影响。目标:我们的目标是比较移植后第一年有或没有临床诊断为 GERD 的肺移植受者的同种异体移植物微生物群,并评估 GERD、同种异体移植物微生物群、炎症和急性和慢性肺同种异体移植物功能障碍(ALAD 和 CLAD)之间的关联。方法:在移植后 1 年内,每 3 个月在一个移植中心从 75 名肺移植受者收集共 268 个 BAL 样本。来自独立移植中心的 10 名移植接受者提供了抗反流 Nissen 胃底折叠术前后的样本。分别使用 16S 核糖体 RNA 基因测序和定量聚合酶链反应测量微生物群落组成和密度,并对炎症标志物和胆汁酸进行定量。测量和主要结果:我们观察到一系列同种异体移植物群落组成,具有三种可辨别的类型(标记的群落状态类型 [CST] 1-3)。患有 GERD 的移植受者更可能患有 CST1,其特征是口咽部普雷沃氏菌属和韦荣氏菌属的高细菌密度和相对丰度。GERD 与更频繁地过渡到 CST1 相关。在观察到的微生物密度范围内,与病原体主导的 CST3 相比,CST1 与较低的炎症细胞因子浓度相关。Cox 比例风险模型揭示了 CST3 与 ALAD/CLAD 发展之间的关联。Nissen 胃底折叠术减少了细菌负荷和促炎细胞因子。结论:GERD 与高细菌密度、Prevotella 和 Veillonella 为主的 CST1 相关。CST3,而不是 CST1 或 GERD,与炎症和 ALAD 和 CLAD 的早期发展相关。Nissen 胃底折叠术与 BAL 液样本中微生物密度的降低有关,尤其是 CST1 特异性普雷沃菌属。
更新日期:2022-07-23
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