Transcriptomic Profile of Whole Blood Cells from Elderly Subjects Fed Probiotic Bacteria Lactobacillus rhamnosus GG ATCC 53103 (LGG) in a Phase I Open Label Study.
Transcriptomic Profile of Whole Blood Cells from Elderly Subjects Fed Probiotic Bacteria Lactobacillus rhamnosus GG ATCC 53103 (LGG) in a Phase I Open Label Study.
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DOI：
10.1371/journal.pone.0147426
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Hibberd PL
中科院分区：
文献类型：
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作者：
Solano-Aguilar G;Molokin A;Botelho C;Fiorino AM;Vinyard B;Li R;Chen C;Urban J Jr;Dawson H;Andreyeva I;Haverkamp M;Hibberd PL
我们使用RNA测序（RNA-Seq）检查了来自参与I期开放标签研究的11名健康老年志愿者在用鼠李糖乳杆菌GG-ATCC 53103（LGG）口服治疗之前和之后的全血细胞（WBC）的基因表达。老年患者（65-80岁）完成了健康状况的临床评估，并在研究入院时（基线）、每日LGG治疗28天后（第28天）和LGG治疗暂停28天后研究结束时（第56天）抽血用于细胞RNA提取。通过测量宿主粪便样品中检测到的LGG-DNA拷贝水平来验证治疗依从性。使用在通常用于基因计数数据分析的三个分析平台（edgeR、DESeq 2和TSPM）内构建的配对设计分析WBC RNA中的标准化基因表达水平。从检测到的25，990个转录物中，所有分析平台共同检测到95个差异表达基因（DEG），在LGG处理后第28天基因表达存在名义上的显著差异（FDR<0.1; 77个降低，18个增加）。在更严格的显著性阈值（FDR<0.05）下，只有两个基因（FCER 2和LY 86）下调超过1.5倍，并且满足两个分析平台的差异表达标准。其余93个基因仅在该阈值水平下用DESeq 2平台检测到。绝对倍数变化为1.5的DEG的生物学解释的数据分析揭示了涉及细胞运动、细胞与细胞信号传导相互作用、免疫细胞运输和炎症反应的重叠基因的下调。这些数据为健康老年志愿者中LGG诱导的转录调节提供了证据，因为在LGG治疗停止后28天恢复了治疗前的转录水平。为了深入了解响应于LGG处理而受影响的信号传导途径，使用生物学途径和基因组数据挖掘包绘制DEG以指示显著的生物学相关性。试用注册：ClinicalTrials.gov NCT 01274598
We examined gene expression of whole blood cells (WBC) from 11 healthy elderly volunteers participating on a Phase I open label study before and after oral treatment with Lactobacillus rhamnosus GG-ATCC 53103 (LGG)) using RNA-sequencing (RNA-Seq). Elderly patients (65–80 yrs) completed a clinical assessment for health status and had blood drawn for cellular RNA extraction at study admission (Baseline), after 28 days of daily LGG treatment (Day 28) and at the end of the study (Day 56) after LGG treatment had been suspended for 28 days. Treatment compliance was verified by measuring LGG-DNA copy levels detected in host fecal samples. Normalized gene expression levels in WBC RNA were analyzed using a paired design built within three analysis platforms (edgeR, DESeq2 and TSPM) commonly used for gene count data analysis. From the 25,990 transcripts detected, 95 differentially expressed genes (DEGs) were detected in common by all analysis platforms with a nominal significant difference in gene expression at Day 28 following LGG treatment (FDR<0.1; 77 decreased and 18 increased). With a more stringent significance threshold (FDR<0.05), only two genes (FCER2 and LY86), were down-regulated more than 1.5 fold and met the criteria for differential expression across two analysis platforms. The remaining 93 genes were only detected at this threshold level with DESeq2 platform. Data analysis for biological interpretation of DEGs with an absolute fold change of 1.5 revealed down-regulation of overlapping genes involved with Cellular movement, Cell to cell signaling interactions, Immune cell trafficking and Inflammatory response. These data provide evidence for LGG-induced transcriptional modulation in healthy elderly volunteers because pre-treatment transcription levels were restored at 28 days after LGG treatment was stopped. To gain insight into the signaling pathways affected in response to LGG treatment, DEG were mapped using biological pathways and genomic data mining packages to indicate significant biological relevance. Trial Registration: ClinicalTrials.gov NCT01274598