最近出现的证据显示肠道菌群在胰腺导管腺癌（PDAC）中起着突出的作用。然而，虽然大多数观察是在患者中进行的，但小鼠模型仍然需要精确地表征与疾病相关的菌群，以便将其用于机制和干预性临床前研究。为了调查LSL-KrasG12D / +; LSL-Trp53R172H / +; Pdx-1-Cre（KPC）和对照（CTRL）小鼠的粪便和肿瘤菌群，我们采用了牛津纳米孔测序方法。从10只KPC小鼠和10只CTRL小鼠分别收集到粪便样本，分别在3个时间点（6周，12周，肿瘤发生时（KPC）或6个月后（CTRL））进行实验。通过对粪便DNA进行宏基因组测序，并对KPC肿瘤和健康胰腺的DNA样本进行16S rRNA基因测序。通过荧光原位杂交（FISH）和免疫组织化学（IHC）检测，发现KPC肿瘤组织中的细菌标记成分随时间变化。小鼠粪便样本的微生物组与同龄健康的CTRL小鼠相比在beta多样性方面存在显著差异（p = 0.001，Bray-Curtis的R2值为0.2-0.25）。经过调整的人类PDAC分类器预测了来自KPC小鼠粪便的疾病状态，其接收者操作特征曲线（AUROC）值为80%。此外，KPC肿瘤中的细菌组分明显多于健康胰腺。此外，KPC肿瘤与健康胰腺组织的微生物组成差异也显著（Bray-Curtis的p值为0.042）。在人类PDAC样本中高度丰富的微生物群落在KPC肿瘤中明显比健康胰腺样本更丰富（p值<0.001）。KPC粪便样本的微生物组成与人类PDAC患者的大便样本的微生物组成相似。Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.

Emerging evidence has recently revealed a prominent role of the microbiome in pancreatic ductal adenocarcinoma (PDAC). However, while most observations were made in patients, mouse models still require a precise characterization of their disease-related microbiome to employ them for mechanistic and interventional preclinical studies.To investigate the fecal and tumoral microbiome of LSL-KrasG12D/+;LSL-Trp53R172H/+;Pdx-1-Cre (KPC) and control (CTRL) mice, Oxford Nanopore sequencing was applied. Feces were collected from 10 KPC mice and 10 CTRLs at 3 timepoints (6 weeks, 12 weeks, and when tumor-bearing (KPC) or 6 months (CTRL), respectively). Metagenomic sequencing was performed on feces DNA. KPC tumor and healthy pancreas DNA samples were subjected to 16S rRNA gene sequencing. Bacterial marker components were detected in KPC tumor tissue over time by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC).Murine fecal samples showed a significantly different microbiome compared to age-matched healthy CTRLs regarding beta diversity (p = 0.001, R2 = 0.2-0.25 for Bray-Curtis). Adjusted human PDAC classifiers predicted disease status from feces of KPC mice achieving area under the receiver operating characteristic (AUROC) values of 80%. Furthermore, KPC tumors harbored significantly more bacterial components than healthy pancreas. Also the microbial composition differs significantly between KPC tumors and healthy pancreas tissue (p = 0.042 for Bray-Curtis). Microbiota found highly abundant in human PDAC samples were considerably more abundant in KPC tumors as compared to healthy pancreas samples (p-value <0.001).KPC fecal samples show similarities with the microbial composition of stool samples from human PDAC patients.Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.