Cftr deletion in mouse epithelial and immune cells differentially influence the intestinal microbiota.
Cftr deletion in mouse epithelial and immune cells differentially influence the intestinal microbiota.
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DOI：
10.1038/s42003-022-04101-5
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发表时间：
2022-10-26
影响因子：
5.9
通讯作者：
中科院分区：
文献类型：
--
作者：
囊性纤维化 (CF) 是一种危及生命的遗传性疾病，由 CF 跨膜电导调节基因 (cftr) 突变引起，该基因编码 CFTR（一种 cAMP 激活的氯离子和碳酸氢根通道）。临床上，CF肺病在成年患者群体中占主导地位。然而，其胃肠道疾病的发病率和死亡率较高，表现为肠道菌群失调、炎症和梗阻。由于 CF 被广泛认为是一种上皮功能障碍疾病，因此尚不清楚免疫细胞中 CFTR 功能丧失是否会导致这些临床结果。利用 cftr 基因敲除和骨髓移植小鼠模型，我们对肠道微生物进行了 16S rRNA 基因测序。在这里，我们发现上皮细胞和免疫细胞中的 cftr 缺失共同影响肠道微生物群。然而，免疫缺陷是决定小肠菌群失调的主要因素，而上皮缺陷则在很大程度上影响大肠菌群失调。这一发现修正了当前的概念，表明 CF 上皮缺陷和免疫缺陷在 CF 肠道疾病中发挥着不同的作用。上皮细胞和免疫细胞中的囊性纤维化跨膜电导调节因子（cftr）基因功能对小鼠肠道微生物群产生不同的影响。
Cystic fibrosis (CF) is a life-threatening genetic disorder, caused by mutations in the CF transmembrane-conductance regulator gene (cftr) that encodes CFTR, a cAMP-activated chloride and bicarbonate channel. Clinically, CF lung disease dominates the adult patient population. However, its gastrointestinal illness claims the early morbidity and mortality, manifesting as intestinal dysbiosis, inflammation and obstruction. As CF is widely accepted as a disease of epithelial dysfunction, it is unknown whether CFTR loss-of-function in immune cells contributes to these clinical outcomes. Using cftr genetic knockout and bone marrow transplantation mouse models, we performed 16S rRNA gene sequencing of the intestinal microbes. Here we show that cftr deletion in both epithelial and immune cells collectively influence the intestinal microbiota. However, the immune defect is a major factor determining the dysbiosis in the small intestine, while the epithelial defect largely influences that in the large intestine. This finding revises the current concept by suggesting that CF epithelial defect and immune defect play differential roles in CF intestinal disease. The cystic fibrosis transmembrane-conductance regulator (cftr) gene function in epithelial and immune cells affect gut microbiome in mice differently.
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影响因子：
2.6
作者：
Gu, Min;Samuelson, Derrick R.;de la Rua, Nicholas M.;Charles, Tysheena P.;Taylor, Christopher M.;Luo, Meng;Siggins, Robert W.;Shellito, Judd E.;Welsh, David A.
通讯作者：
Welsh, David A.
影响因子：
48
作者：
Callahan BJ;McMurdie PJ;Rosen MJ;Han AW;Johnson AJ;Holmes SP
通讯作者：
Holmes SP
影响因子：
4.8
作者：
Furdui, C;Ragsdale, SW
通讯作者：
Ragsdale, SW
囊性纤维化。
影响因子：
1.3
作者：
Dickinson KM;Collaco JM
通讯作者：
Collaco JM
影响因子：
5.4
作者：
De Lisle, Robert C.;Borowitz, Drucy
通讯作者：
Borowitz, Drucy