Compositionally and functionally distinct sinus microbiota in chronic rhinosinusitis patients have immunological and clinically divergent consequences.
Compositionally and functionally distinct sinus microbiota in chronic rhinosinusitis patients have immunological and clinically divergent consequences.
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DOI：
10.1186/s40168-017-0266-6
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发表时间：
2017-05-12
期刊：
影响因子：
15.5
通讯作者：
Lynch SV
中科院分区：
文献类型：
--
作者：
Cope EK;Goldberg AN;Pletcher SD;Lynch SV
慢性鼻窦炎（CRS）是一种异质性疾病，其特征为持续性鼻窦炎症和鼻窦微生物群失调。这种异质性的基础尚未被充分了解。我们试图验证一个假设，即慢性鼻窦炎患者中存在数量有限的成分不同的致病性细菌微生物群，并在慢性鼻窦炎患者中引发不同的免疫反应和临床表型。
在内镜鼻窦手术期间收集的慢性鼻窦炎患者（n = 59）和健康个体（n = 10）的鼻窦刷取物，通过16S rRNA基因测序、预测宏基因组学以及黏膜免疫反应的RNA分析进行了研究。我们发现慢性鼻窦炎患者聚类为不同的亚组（DSI - III），每个亚组由特定的细菌共定植模式所定义（置换多元方差分析（PERMANOVA）；p = 0.001，r² = 0.318）。每个亚组通常由一个致病家族主导：链球菌科（DSI）、假单胞菌科（DSII）、棒状杆菌科[DSIII（a）]或葡萄球菌科[DSIII（b）]。预测每个致病性微生物群在功能上是不同的（置换多元方差分析（PERMANOVA）；p = 0.005，r² = 0.217），并且编码独特富集的基因通路，包括安莎霉素生物合成（DSI）、色氨酸代谢（DSII）、双组分反应[DSIII（b）]以及过氧化物酶体增殖物激活受体 - γ信号通路[DSIII（a）]。每个亚组也与明显不同的宿主免疫反应相关；DSI、II和III（b）引发多种促炎、TH1反应，而DSIII（a）鼻息肉发生率显著增加（费舍尔精确检验；p = 0.034，相对风险 = 2.16），主要诱导白细胞介素 - 5表达（克鲁斯卡尔 - 沃利斯检验；q = 0.045）。
慢性鼻窦炎患者的大部分异质性可以通过其鼻窦细菌微生物群的组成以及相关的宿主免疫反应来解释——这些特征可能为该患者群体的个体化治疗策略提供依据。
本文的在线版本（doi:10.1186/s40168 - 017 - 0266 - 6）包含补充材料，授权用户可获取。
Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by persistent sinonasal inflammation and sinus microbiome dysbiosis. The basis of this heterogeneity is poorly understood. We sought to address the hypothesis that a limited number of compositionally distinct pathogenic bacterial microbiota exist in CRS patients and invoke discrete immune responses and clinical phenotypes in CRS patients. Sinus brushings from patients with CRS (n = 59) and healthy individuals (n = 10) collected during endoscopic sinus surgery were analyzed using 16S rRNA gene sequencing, predicted metagenomics, and RNA profiling of the mucosal immune response. We show that CRS patients cluster into distinct sub-groups (DSI-III), each defined by specific pattern of bacterial co-colonization (permutational multivariate analysis of variance (PERMANOVA); p = 0.001, r 2 = 0.318). Each sub-group was typically dominated by a pathogenic family: Streptococcaceae (DSI), Pseudomonadaceae (DSII), Corynebacteriaceae [DSIII(a)], or Staphylococcaceae [DSIII(b)]. Each pathogenic microbiota was predicted to be functionally distinct (PERMANOVA; p = 0.005, r 2 = 0.217) and encode uniquely enriched gene pathways including ansamycin biosynthesis (DSI), tryptophan metabolism (DSII), two-component response [DSIII(b)], and the PPAR-γ signaling pathway [DSIII(a)]. Each is also associated with significantly distinct host immune responses; DSI, II, and III(b) invoked a variety of pro-inflammatory, TH1 responses, while DSIII(a), which exhibited significantly increased incidence of nasal polyps (Fisher’s exact; p = 0.034, relative risk = 2.16), primarily induced IL-5 expression (Kruskal Wallis; q = 0.045). A large proportion of CRS patient heterogeneity may be explained by the composition of their sinus bacterial microbiota and related host immune response—features which may inform strategies for tailored therapy in this patient population. The online version of this article (doi:10.1186/s40168-017-0266-6) contains supplementary material, which is available to authorized users.