Background Increasing evidence implicates microbiome involvement in the development and progression of pancreatic ductal adenocarcinoma (PDAC). Studies suggest that reflux of gut or oral microbiota can lead to colonization in the pancreas, resulting in dysbiosis that culminates in release of microbial toxins and metabolites that potentiate an inflammatory response and increase susceptibility to PDAC. Moreover, microbe-derived metabolites can exert direct effector functions on precursors and cancer cells, as well as other cell types, to either promote or attenuate tumor development and modulate treatment response. Content The occurrence of microbial metabolites in biofluids thereby enables risk assessment and prognostication of PDAC, as well as having potential for design of interception strategies. In this review, we first highlight the relevance of the microbiome for progression of precancerous lesions in the pancreas and, using liquid chromatography–mass spectrometry, provide supporting evidence that microbe-derived metabolites manifest in pancreatic cystic fluid and are associated with malignant progression of intraductal papillary mucinous neoplasm(s). We secondly summarize the biomarker potential of microbe-derived metabolite signatures for (a) identifying individuals at high risk of developing or harboring PDAC and (b) predicting response to treatment and disease outcomes. Summary The microbiome-derived metabolome holds considerable promise for risk assessment and prognostication of PDAC.

中文翻译：

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微生物组衍生的代谢组对胰腺癌风险评估和预后的贡献

背景 越来越多的证据表明微生物组参与胰腺导管腺癌 (PDAC) 的发生和进展。研究表明，肠道或口腔微生物群的回流可导致胰腺定植，导致菌群失调，最终导致微生物毒素和代谢物的释放，从而增强炎症反应并增加对 PDAC 的易感性。此外，微生物衍生的代谢物可以对前体细胞和癌细胞以及其他细胞类型发挥直接效应功能，以促进或减弱肿瘤发展并调节治疗反应。内容因此，生物体液中微生物代谢物的出现使得 PDAC 的风险评估和预测成为可能，并且具有设计拦截策略的潜力。在这篇综述中，我们首先强调微生物组与胰腺癌前病变进展的相关性，并使用液相色谱-质谱法提供支持证据，证明微生物衍生的代谢物出现在胰腺囊液中，并与导管内癌的恶性进展相关。乳头状粘液性肿瘤。其次，我们总结了微生物衍生代谢特征的生物标志物潜力，用于 (a) 识别具有发展或携带 PDAC 高风险的个体，以及 (b) 预测对治疗和疾病结果的反应。摘要 微生物组衍生的代谢组对于 PDAC 的风险评估和预测具有很大的前景。