Variations of oral microbiota are associated with pancreatic diseases including pancreatic cancer.

Variations of oral microbiota are associated with pancreatic diseases including pancreatic cancer.
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DOI:
10.1136/gutjnl-2011-300784
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发表时间:
2012-04
期刊:
Gut
影响因子:
24.5
通讯作者:
Wong DT
Wong DT
中科院分区:
医学1区
文献类型:
--
作者:
Farrell JJ;Zhang L;Zhou H;Chia D;Elashoff D;Akin D;Paster BJ;Joshipura K;Wong DT

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口腔疾病和胰腺癌风险增加之间的关联已在几项前瞻性队列研究中报道。在这项研究中,我们测量了唾液微生物群的变化,并评估了它们与胰腺癌和慢性胰腺炎的潜在关联。本研究分为三个阶段:(1)使用人类口腔微生物鉴定微阵列的微生物谱分析,以研究10名可切除的胰腺癌患者和10名匹配的健康对照之间的唾液微生物群变化,(2)通过实时定量PCR(qPCR)鉴定和验证细菌候选物,以及(3)通过qPCR对28个可切除的胰腺癌、28个匹配的健康对照和27个慢性胰腺炎样品的独立队列验证细菌候选物。胰腺癌患者和健康对照受试者之间唾液微生物群的综合比较揭示了唾液微生物群的显著变化。胰腺癌患者(n = 10)唾液中的31种细菌/簇与健康对照组(n = 10)相比有所增加,而25种细菌/簇则有所减少。使用独立样品验证六种细菌候选物中的两种(细长奈瑟氏球菌和缓症链球菌),显示胰腺癌患者和对照(n=56)之间的显著变化(p<0.05,qPCR)。此外,两种细菌(颗粒状芽孢杆菌和缓症芽孢杆菌)在慢性胰腺炎样品和对照(n=55)之间显示出显著变化(p<0.05,qPCR)。两种细菌生物标志物(细长亚硝化单胞菌和缓症亚硝化单胞菌)的组合产生了0.90(95%CI 0.78至0.96,p<0.0001)的受试者操作特征曲线下面积,在区分胰腺癌患者与健康受试者方面具有96.4%的灵敏度和82.1%的特异性。作者观察了患者唾液微生物群的变化与胰腺癌和慢性胰腺炎之间的关系。该报告还提供了唾液微生物群作为发现全身性疾病的非侵入性生物标志物的信息来源的证据。
The associations between oral diseases and increased risk of pancreatic cancer have been reported in several prospective cohort studies. In this study, we measured variations of salivary microbiota and evaluated their potential associations with pancreatic cancer and chronic pancreatitis. This study was divided into three phases: (1) microbial profiling using the Human Oral Microbe Identification Microarray to investigate salivary microbiota variation between 10 resectable patients with pancreatic cancer and 10 matched healthy controls, (2) identification and verification of bacterial candidates by real-time quantitative PCR (qPCR) and (3) validation of bacterial candidates by qPCR on an independent cohort of 28 resectable pancreatic cancer, 28 matched healthy control and 27 chronic pancreatitis samples. Comprehensive comparison of the salivary microbiota between patients with pancreatic cancer and healthy control subjects revealed a significant variation of salivary microflora. Thirty-one bacterial species/clusters were increased in the saliva of patients with pancreatic cancer (n=10) in comparison to those of the healthy controls (n=10), whereas 25 bacterial species/clusters were decreased. Two out of six bacterial candidates (Neisseria elongata and Streptococcus mitis) were validated using the independent samples, showing significant variation (p<0.05, qPCR) between patients with pancreatic cancer and controls (n=56). Additionally, two bacteria (Granulicatella adiacens and S mitis) showed significant variation (p<0.05, qPCR) between chronic pancreatitis samples and controls (n=55). The combination of two bacterial biomarkers (N elongata and S mitis) yielded a receiver operating characteristic plot area under the curve value of 0.90 (95% CI 0.78 to 0.96, p<0.0001) with a 96.4% sensitivity and 82.1% specificity in distinguishing patients with pancreatic cancer from healthy subjects. The authors observed associations between variations of patients’ salivary microbiota with pancreatic cancer and chronic pancreatitis. This report also provides proof of salivary microbiota as an informative source for discovering non-invasive biomarkers of systemic diseases.
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