A Simple and Novel Fecal Biomarker for Colorectal Cancer: Ratio of Fusobacterium Nucleatum to Probiotics Populations, Based on Their Antagonistic Effect
A Simple and Novel Fecal Biomarker for Colorectal Cancer: Ratio of Fusobacterium Nucleatum to Probiotics Populations, Based on Their Antagonistic Effect
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一种简单而新颖的结直肠癌粪便生物标志物：具核梭杆菌与益生菌群的比例，基于其拮抗作用。
DOI：
10.1373/clinchem.2018.289728
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发表时间：
2018-09-01
影响因子：
9.3
通讯作者：
Zhang, Ge
中科院分区：
文献类型：
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作者：
Guo, Songhe;Li, Linfang;Zhang, Ge
背景：肠道微生物生态失调有助于结直肠癌（CRC）的发展。我们评估了通过我们的16S rDNA测序分析确定的粪便细菌生物标志物候选物在CRC诊断中的效用。方法：采用定量PCR的方法，对2组903人的粪便样本进行了核梭杆菌（Fn）、prausnitzii粪杆菌（Fp）、双歧杆菌（Bb）和乳杆菌（Lb）的相对丰度检测。我们评估并验证了这些微生物比例的诊断性能，并研究了Fn对3种不同指示剂的拮抗作用。结果：Fn/Bb微生物比（Fn/Bb）检测结直肠癌的敏感性为84.6%，特异性为92.3%（曲线下面积，AUC = 0.911）。Fn/Bb和Fn/Fp联合检测提高了诊断价值（AUC = 0.943）。Fn/Bb和Fn/Fp联合检测CRC I期的特异性为60.0%，敏感性为90.0% （AUC = 0.804）。特别是在CRC组中，Fn与Fp呈负相关。在验证队列II中证实了CRC诊断的性能。Fn培养上清液对益生菌Fp和Bb有较强的杀菌活性。结论：本研究发现Fn可能通过分泌对益生菌的拮抗物质在菌群失调中发挥作用。此外，Fn与重要益生菌Fp和Bb的比值被确定为筛查早期结直肠癌的有价值的生物标志物。(c) 2018年美国临床化学协会。
BACKGROUND: Gut microbial dysbiosis contributes to the development of colorectal cancer (CRC). We evaluated the utility of fecal bacterial biomarker candidates identified by our 16S rDNA sequencing analysis for CRC diagnosis.METHODS: We measured the relative abundance of Fusobacterium nucleatum (Fn), Faecalibacterium prausnitzii (Fp), Bifidobacterium (Bb), and Lactobacillus (Lb) by quantitative PCR in fecal samples from 2 cohorts of 903 individuals. We evaluated and validated the diagnostic performance of these microbial ratios and investigated the antagonistic effect of Fn against 3 different indicator stains.RESULTS: The microbial ratio of Fn to Bb (Fn/Bb) had a superior sensitivity of 84.6% and specificity of 92.3% in detecting CRC (area under the curve, AUC = 0.911). The combination of Fn/Bb and Fn/Fp improved the diagnostic value (AUC = 0.943). Moreover, the combination of Fn/Bb and Fn/Fp offered 60.0% specificity and 90.0% sensitivity in detecting stage I of CRC (AUC = 0.804). In particular, Fn was negatively correlated with Fp in the CRC group. The performance for CRC diagnosis was confirmed in the validation cohort II. The culture supernatant from Fn exhibited strong bactericidal activity against probiotics Fp and Bb strains.CONCLUSIONS: This study found that Fn could play a role in microbiota dysbiosis via the secreted antagonistic substances against probiotics. Moreover, the ratio of Fn to the important probiotics Fp and Bb was identified as a valuable biomarker for screening early CRC. (c) 2018 American Association for Clinical Chemistry.