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揭示肠道微生物组对胰腺导管腺癌的贡献:机制见解与治疗前景

英文原题:Unraveling the gut microbiome's contribution to pancreatic ductal adenocarcinoma: mechanistic insights and therapeutic perspectives.

查看英文原题

Unraveling the gut microbiome's contribution to pancreatic ductal adenocarcinoma: mechanistic insights and therapeutic perspectives.

PubMed 2024/07/09(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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中文摘要

肠道微生物组参与胰腺导管腺癌的发生发展,影响致癌、免疫反应和治疗结局。牙龈卟啉单胞菌和具核梭杆菌等微生物可通过多种机制促进疾病进展。肠道微生物也影响免疫细胞活化及免疫检查点抑制剂、CAR-T 等免疫治疗反应。特定微生物及其代谢物影响检查点抑制疗效;微生物组变化可增强或削弱PD-1/PD-L1及CTLA-4阻断效果。三甲胺-N-氧化物和脂多糖等细菌代谢物可调节抗肿瘤免疫,可能成为增敏靶点。粪菌移植、益生菌、益生元、饮食调整和抗生素调节微生物组显示治疗潜力,但结果差异较大。高纤维和特定脂肪摄入也会影响菌群及癌症风险。微生物组疗法与现有治疗联合可能改善胰腺癌结局,仍需研究优化方案。

展开英文摘要原文

The gut microbiome plays a significant role in the pathogenesis of pancreatic ductal adenocarcinoma (PDAC), influencing oncogenesis, immune responses, and treatment outcomes. Studies have identified microbial species like Porphyromonas gingivalis and Fusobacterium nucleatum, that promote PDAC progression through various mechanisms.

Additionally, the gut microbiome affects immune cell activation and response to immunotherapy, including immune checkpoint inhibitors and CAR-T therapy. Specific microbes and their metabolites play a significant role in the effectiveness of immune checkpoint inhibitors (ICIs). Alterations in the gut microbiome can either enhance or diminish responses to PD-1/PD-L1 and CTLA-4 blockade therapy.

Additionally, bacterial metabolites like trimethylamine N-oxide (TMAO) and lipopolysaccharide (LPS) impact antitumor immunity, offering potential targets to augment immunotherapy responses. Modulating the microbiome through fecal microbiota transplantation, probiotics, prebiotics, dietary changes, and antibiotics shows promise in PDAC treatment, although outcomes are highly variable.

Dietary modifications, particularly high-fiber diets and specific fat consumption, influence microbiome composition and impact cancer risk. Combining microbiome-based therapies with existing treatments holds potential for improving PDAC therapy outcomes, but further research is needed to optimize their effectiveness.

论文信息

作者
Tabrizi E、Pourteymour Fard Tabrizi F、Mahmoud Khaled G、Sestito MP、Jamie S、Boone BA
单位
Department of Microbiology, Immunology and Cell Biology, School of Medicine, West Virginia University, Morgantown, WV, United States.United States
文献类型
综述
期刊
Frontiers in immunology2024
原文标识
PubMed 39044834 · DOI 10.3389/fimmu.2024.1434771