Department of Gastroenterological Endoscopy, Tokyo Medical University, Tokyo, Japan; Department of Gastroenterology and Hepatology, National Center for Global Health and Medicine, Tokyo, Japan.
Computational Bio-Big Data Open Innovation Lab, National Institute of Advanced Industrial Science and Technology, Tokyo, Japan; Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, Japan; Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
Gastroenterology. 2022 Jul;163(1):222-238. doi: 10.1053/j.gastro.2022.03.054. Epub 2022 Apr 8.
BACKGROUND & AIMS: To identify gut and oral metagenomic signatures that accurately predict pancreatic ductal carcinoma (PDAC) and to validate these signatures in independent cohorts.
We conducted a multinational study and performed shotgun metagenomic analysis of fecal and salivary samples collected from patients with treatment-naïve PDAC and non-PDAC controls in Japan, Spain, and Germany. Taxonomic and functional profiles of the microbiomes were characterized, and metagenomic classifiers to predict PDAC were constructed and validated in external datasets.
Comparative metagenomics revealed dysbiosis of both the gut and oral microbiomes and identified 30 gut and 18 oral species significantly associated with PDAC in the Japanese cohort. These microbial signatures achieved high area under the curve values of 0.78 to 0.82. The prediction model trained on the Japanese gut microbiome also had high predictive ability in Spanish and German cohorts, with respective area under the curve values of 0.74 and 0.83, validating its high confidence and versatility for PDAC prediction. Significant enrichments of Streptococcus and Veillonella spp and a depletion of Faecalibacterium prausnitzii were common gut signatures for PDAC in all the 3 cohorts. Prospective follow-up data revealed that patients with certain gut and oral microbial species were at higher risk of PDAC-related mortality. Finally, 58 bacteriophages that could infect microbial species consistently enriched in patients with PDAC across the 3 countries were identified.
Metagenomics targeting the gut and oral microbiomes can provide a powerful source of biomarkers for identifying individuals with PDAC and their prognoses. The identification of shared gut microbial signatures for PDAC in Asian and European cohorts indicates the presence of robust and global gut microbial biomarkers.
鉴定能够准确预测胰腺导管腺癌（PDAC）的肠道和口腔宏基因组特征，并在独立队列中验证这些特征。
我们进行了一项多国家研究，对来自日本、西班牙和德国未经治疗的 PDAC 患者和非 PDAC 对照者的粪便和唾液样本进行了 shotgun 宏基因组分析。对微生物组的分类和功能谱进行了表征，并构建和验证了外部数据集预测 PDAC 的宏基因组分类器。
比较宏基因组学揭示了肠道和口腔微生物组的失调，并在日本队列中鉴定出 30 种与 PDAC 显著相关的肠道物种和 18 种口腔物种。这些微生物特征的曲线下面积值达到 0.78 至 0.82。在西班牙和德国队列中，基于日本肠道微生物组建立的预测模型也具有较高的预测能力，相应的曲线下面积值分别为 0.74 和 0.83，验证了其对 PDAC 预测的高可信度和多功能性。在所有 3 个队列中，链球菌属和韦荣球菌属的丰度增加以及粪肠球菌属的减少是 PDAC 的常见肠道特征。前瞻性随访数据显示，具有某些肠道和口腔微生物物种的患者患 PDAC 相关死亡的风险更高。最后，在 3 个国家的 PDAC 患者中一致富集的微生物物种中鉴定出 58 种可能感染的噬菌体。
针对肠道和口腔微生物组的宏基因组学可以为识别 PDAC 患者及其预后提供强大的生物标志物来源。在亚洲和欧洲队列中鉴定出 PDAC 的共享肠道微生物特征表明存在稳健且具有全球意义的肠道微生物生物标志物。
