Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing, China.
Microbiol Spectr. 2024 Nov 5;12(11):e0096224. doi: 10.1128/spectrum.00962-24. Epub 2024 Oct 10.
Pancreatic cancer, predominantly pancreatic ductal adenocarcinoma (PDAC), is one of the most malignant tumors of the digestive system. Emerging evidence suggests the involvement of the microbiome and metabolic substances in the development of PDAC, yet the results remain contradictory. This study aims to identify the alterations and relationships in intratumoral microbiome and metabolites in PDAC. We collected matched tumor and normal adjacent tissue (NAT) samples from 105 PDAC patients and performed a 6-year follow-up. 2bRAD-M sequencing, untargeted liquid chromatography-tandem mass spectrometry, and untargeted gas chromatography-mass spectrometry were performed. Compared with NATs, microbial α-diversity decreased in PDAC tumors. The relative abundance of , and was higher in PDAC tumor after adjusting for confounding factors body mass index and M stage, and the presence of was found associated with a worse overall survival. Metabolomic analysis revealed distinctive differences in composition between PDAC and NAT, with 553 discriminative metabolites identified. Differential metabolites were revealed to originate from the microbiota and showed significant interactions with shifted bacterial species through KO (KEGG Orthology) genes. These findings suggest that the PDAC microenvironment harbors unique microbial-derived enzymatic reactions, potentially influencing the occurrence and development of PDAC by modulating the levels of glycerol-3-phosphate, succinate, carbonate, and beta-alanine.
We conducted a large sample-size pancreatic adenocarcinoma microbiome study using a novel microbiome sequencing method and two metabolomic assays. Two significant outcomes of our analysis are: (i) commensal opportunistic pathogens , , and were enriched in pancreatic ductal adenocarcinoma (PDAC) tumors compared with normal adjacent tissues, and (ii) worse overall survival was found related to the presence of . Microbial species affect the tumorigenesis, metastasis, and prognosis of PDAC via unique microbe-enzyme-metabolite interaction. Thus, our study highlights the need for further investigation of the potential associations between pancreatic microbiota-derived omics signatures, which may drive the clinical transformation of microbiome-derived strategies toward therapy-targeted bacteria.
胰腺癌，主要是胰腺导管腺癌（PDAC），是消化系统中最恶性的肿瘤之一。新出现的证据表明，微生物组和代谢物质参与了 PDAC 的发展，但结果仍存在矛盾。本研究旨在确定 PDAC 肿瘤内微生物组和代谢物的改变和关系。我们收集了 105 名 PDAC 患者的配对肿瘤和正常邻近组织（NAT）样本，并进行了 6 年的随访。进行了 2bRAD-M 测序、非靶向液相色谱-串联质谱和非靶向气相色谱-质谱分析。与 NAT 相比，PDAC 肿瘤中的微生物 α多样性降低。在调整混杂因素体重指数和 M 期后， 、 和 的相对丰度在 PDAC 肿瘤中较高， 的存在与总体生存率较差相关。代谢组学分析显示 PDAC 和 NAT 之间在组成上存在明显差异，鉴定出 553 种有区别的代谢物。差异代谢物来源于微生物群，通过 KO（KEGG 直系同源）基因与移位细菌物种显示出显著的相互作用。这些发现表明，PDAC 微环境中存在独特的微生物衍生酶反应，通过调节甘油-3-磷酸、琥珀酸、碳酸盐和β-丙氨酸的水平，可能影响 PDAC 的发生和发展。
我们使用一种新的微生物组测序方法和两种代谢组学检测方法进行了大规模的胰腺腺癌微生物组研究。我们分析的两个重要结果是：（i）与正常邻近组织相比，机会性共生病原体 、 和 在胰腺导管腺癌（PDAC）肿瘤中富集，（ii）总体生存率较差与 的存在有关。微生物物种通过独特的微生物-酶-代谢物相互作用影响 PDAC 的发生、转移和预后。因此，我们的研究强调需要进一步研究胰腺微生物组衍生的omics 特征与潜在的关联，这可能推动微生物组衍生策略向针对治疗的细菌的临床转化。
