Data Sheet 2_The close association of Muribaculum and PA (10:0/a-17:0) with the occurrence of pancreatic ductal adenocarcinoma and immunotherapy.docx

BackgroundProgress in immunotherapy for pancreatic ductal adenocarcinoma (PDAC) has been slow, yet the relationship between microorganisms and metabolites is crucial to PDAC development. This study compares the biliary microbiota and metabolomic profiles of PDAC patients with those of benign pancreatic disease patients to investigate PDAC pathogenesis and its relationship with immunotherapy.
MethodsA total of 27 patients were recruited, including 15 diagnosed with PDAC and 12 with benign pancreaticobiliary conditions, all of whom underwent surgical treatment. Intraoperative bile samples were collected and analyzed using 16S rRNA sequencing in conjunction with liquid chromatography-mass spectrometry (LC-MS). Multivariate statistical methods and correlation analyzes were employed to assess differences in microbial composition, structure, and function between malignant and benign pancreatic diseases. Additionally, a retrospective analysis was conducted on PDAC patients post-surgery regarding immunotherapy and its correlation with metabolic components.
ResultsPDAC patients exhibited a significantly higher abundance of bile microbiota compared to controls, with notable differences in microbiota structure between the two groups (P < 0.05). At the genus level, Muribaculum was markedly enriched in the bile of PDAC patients and was strongly correlated with phosphatidic acid (PA) (10:0/a-17:0). Both of these components, along with the tumor marker CA199, formulated a predictor of PDAC. Furthermore, PA (10:0/a-17:0) demonstrated a strong correlation with PDAC immunotherapy outcomes (Rho: 0.758; P=0.011).
ConclusionThese findings suggest that the biliary microbiota and associated metabolites play a crucial role in the development of PDAC and may serve as potential predictive biomarkers and therapeutic targets for disease management.

背景：胰腺导管腺癌（pancreatic ductal adenocarcinoma, PDAC）的免疫治疗进展迟缓，而微生物与代谢物的关联对PDAC的发生发展至关重要。本研究通过对比PDAC患者与胰腺良性疾病患者的胆道微生物群及代谢组谱，旨在探究PDAC的发病机制及其与免疫治疗的关联。
方法：本研究共纳入27例受试者，其中15例确诊为PDAC，12例罹患胰腺胆道良性疾病，所有受试者均接受手术治疗。收集术中胆汁样本，采用16S rRNA测序结合液相色谱-质谱联用（liquid chromatography-mass spectrometry, LC-MS）进行检测分析。通过多变量统计方法与相关性分析，评估良、恶性胰腺疾病患者的微生物组成、结构及功能差异。此外，本研究还对术后PDAC患者开展回顾性分析，探究其免疫治疗情况与代谢组分的相关性。
结果：与对照组相比，PDAC患者的胆道微生物群丰度显著更高，两组微生物群结构存在显著统计学差异（P < 0.05）。在属水平上，Muribaculum在PDAC患者的胆汁中显著富集，且与磷脂酸（phosphatidic acid, PA）(10:0/a-17:0) 呈强相关性。上述两种组分联合肿瘤标志物糖链抗原199（CA199）共同构建了PDAC的预测模型。进一步分析显示，PA(10:0/a-17:0)与PDAC免疫治疗疗效呈显著强相关（Rho: 0.758; P=0.011）。
结论：本研究结果表明，胆道微生物群及其相关代谢物在PDAC的发生发展中发挥关键作用，有望成为疾病管理的潜在预测生物标志物与治疗靶点。