Fecal Microbiota Characteristics of Patients with Colorectal Adenoma Detected by Screening: A Population-based Study.

Fecal Microbiota Characteristics of Patients with Colorectal Adenoma Detected by Screening: A Population-based Study.
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DOI:
10.1016/j.ebiom.2015.04.010
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发表时间:
2015-06
期刊:
影响因子:
11.1
通讯作者:
Zheng Y
Zheng Y
中科院分区:
医学1区
文献类型:
--
作者:
Goedert JJ;Gong Y;Hua X;Zhong H;He Y;Peng P;Yu G;Wang W;Ravel J;Shi J;Zheng Y

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筛查结直肠癌(CRC)和癌前结直肠癌腺瘤(CRA)可以发现可治愈的疾病。然而,参与结肠镜检查和粪便血红素对CRA的敏感性较低。微生物群指标采用Illumina测序,从RNAlater自收集的粪便中提取DNA扩增16S rRNA基因。在粪便免疫化学测试阳性(FIT +)的参与者中,结肠镜定义的正常与CRA患者通过回归、排列和随机森林加留一法进行比较。在95名FIT +参与者中,61名成功进行了粪便微生物群分析和结肠镜检查,确定了24名完全正常患者,20名CRA患者,2名CRC患者和15名其他疾病患者。门水平粪便群落组成在CRA患者和正常患者之间差异显著(排列P = 0.02)。等级门水平丰度将CRA与正常患者区分开来(曲线下面积= 0.767,排列P = 0.006)。门级组B的CRA患病率为59%,组A为20% (P = 0.01)。大部分差异反映了Proteobacteria类群的中位数相对丰度高出3倍(Wilcoxon符号秩P = 0.03,阳性预测值= 67%)。抗生素暴露和其他潜在的混杂因素对这种关联没有影响。如果在更大、更多样化的人群中得到证实,粪便微生物群分析可能用于改善CRA的筛查,并最终降低CRC的死亡率。结直肠腺瘤患者的粪便微生物群组成与正常人不同。大多数差异反映了腺瘤患者中变形杆菌的丰度高出3倍。人群范围内的微生物群筛查是可行的,如果得到验证,可以补充现有的早期检测计划。
Screening for colorectal cancer (CRC) and precancerous colorectal adenoma (CRA) can detect curable disease. However, participation in colonoscopy and sensitivity of fecal heme for CRA are low. Microbiota metrics were determined by Illumina sequencing of 16S rRNA genes amplified from DNA extracted from feces self-collected in RNAlater. Among fecal immunochemical test-positive (FIT +) participants, colonoscopically-defined normal versus CRA patients were compared by regression, permutation, and random forest plus leave-one-out methods. Of 95 FIT + participants, 61 had successful fecal microbiota profiling and colonoscopy, identifying 24 completely normal patients, 20 CRA patients, 2 CRC patients, and 15 with other conditions. Phylum-level fecal community composition differed significantly between CRA and normal patients (permutation P = 0.02). Rank phylum-level abundance distinguished CRA from normal patients (area under the curve = 0.767, permutation P = 0.006). CRA prevalence was 59% in phylum-level cluster B versus 20% in cluster A (exact P = 0.01). Most of the difference reflected 3-fold higher median relative abundance of Proteobacteria taxa (Wilcoxon signed-rank P = 0.03, positive predictive value = 67%). Antibiotic exposure and other potential confounders did not affect the associations. If confirmed in larger, more diverse populations, fecal microbiota analysis might be employed to improve screening for CRA and ultimately to reduce mortality from CRC. Fecal microbiota composition differed for patients with colorectal adenoma compared to normals. Most of the difference reflected 3-fold higher abundance of Proteobacteria in patients with adenoma. Population-wide microbiota screening is feasible and, if validated, could complement established early-detection programs.