Patients with cystic fibrosis (CF) have altered fecal microbiomes compared to those of healthy controls. The magnitude of this dysbiosis correlates with measures of CF gastrointestinal (GI) disease, including GI inflammation and nutrient malabsorption. However, whether this dysbiosis is caused by mutations in the CFTR gene, the underlying defect in CF, or whether CF-associated dysbiosis augments GI disease was not clear. To test the relationships between CFTR dysfunction, microbes, and intestinal health, we established a germ-free (GF) CF mouse model and demonstrated that CFTR gene mutations are sufficient to alter the GI microbiome. Furthermore, flow cytometric analysis demonstrated that colonized CF mice have increased mesenteric lymph node and spleen TH17+ cells compared with non-CF mice, suggesting that CFTR defects alter adaptive immune responses. Our findings demonstrate that CFTR mutations modulate both the host adaptive immune response and the intestinal microbiome.

中文翻译：

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CFTR失调驱动肠道微生物组的主动选择。

与健康对照组相比，囊性纤维化（CF）患者的粪便微生物组已改变。这种营养不良的程度与CF胃肠道（GI）疾病的措施有关，包括GI炎症和营养吸收不良。但是，这种营养不良是否是由CFTR基因突变引起的，CF的潜在缺陷，还是与CF相关的营养不良会加剧GI疾病尚不清楚。为了测试CFTR功能障碍，微生物与肠道健康之间的关系，我们建立了无菌（GF）CF小鼠模型，并证明CFTR基因突变足以改变GI微生物组。此外，流式细胞仪分析表明，与非CF小鼠相比，定植的CF小鼠的肠系膜淋巴结和脾TH17 +细胞增加，提示CFTR缺陷会改变适应性免疫反应。我们的研究结果表明CFTR突变调节宿主的适应性免疫反应和肠道微生物组。