齐豪爽,景元明

胰腺癌是常见的消化道恶性肿瘤之一，近年来其发病率还在不断攀升。肠道菌群作为维持人体健康和免疫系统稳态的一个内在因素，其数量的变化及失衡可能会导致肠内环境的改变，从而影响肿瘤的发生发展。在过去的十年中，一些研究已经表明肠道微生物群在肿瘤的代谢和免疫反应的调节中起着关键作用。在本文中，我们将进一步探讨肠道菌群在胰腺癌发生发展中的影响，并深入研究其在胰腺癌治疗中的潜在作用，为胰腺癌的诊断和治疗提供新的方向。

肠道菌群；胰腺癌；致癌性；治疗

[1]郑荣寿,陈茹,韩冰峰,等.2022 年中国恶性肿瘤流行情况分析[J].中华肿瘤杂志,2024,46(03). [2]Springfeld C,Ferrone C R,Katz M H G,et al.Neoadjuvant therapy for pancreatic cancer[J].Nature Reviews Clinical Oncology,2023, 20(5):318-337. [3]Shalon D,Culver R N,Grembi J A,et al.Profiling the human intestinal environment under physiological conditions[J].Nature,2023:1-11. [4]谢扬帆,曹玲敏,汪雪媛,等.中国胰腺癌患者肠道菌群多样性组成谱的系统评价[J].中国循证医学杂志,2023,23(02):186-190. [5]Hashimoto S,Tochio T,Funasaka K,et al.Changes in intestinal bacteria and imbalances of metabolites induced in the intestines of pancreatic ductal adenocarcinoma patients in a Japanese population:a preliminary result[J].Scandinavian Journal of Gastroenterology, 2023,58(2):193-198. [6]Kohi S,Macgregor-Das A,Dbouk M,et al.Alterations in the duodenal fluid microbiome of patients with pancreatic cancer[J].Clinical Gastroenterology and Hepatology,2022,20(2):e196-e227. [7]Halimi A,Gabarrini G,Sobkowiak M J,et al.Isolation of pancreatic microbiota from cystic precursors of pancreatic cancer with intracellular growth and DNA damaging properties[J].Gut Microbes,2021,13(1):1983101. [8]Nash A K,Auchtung T A,Wong M C,et al.The gut mycobiome of the Human Microbiome Project healthy cohort[J].Microbiome,2017,5: 1-13. [9]Aykut B,Pushalkar S,Chen R,et al.The fungal mycobiome promotes pancreatic oncogenesis via activation of MBL[J].Nature,2019, 574(7777):264-267. [10]Alam A,Levanduski E,Denz P,et al.Fungal mycobiome drives IL-33 secretion and type 2 immunity in pancreatic cancer[J].Cancer Cell,2022,40(2):153-167. [11]Alipour M.Molecular mechanism of Helicobacter pylori-induced gastric cancer[J].Journal of gastrointestinal cancer,2021,52:23-30. [12]Chagneau C V,Payros D,Tang-Fichaux M,et al.The pks island:A bacterial Swiss army knife?Colibactin:Beyond DNA damage and cancer[J].Trends in Microbiology,2022，30(12):1146-1159 [13]Tan Q,Ma X,Yang B,et al.Periodontitis pathogen Porphyromonas gingivalis promotes pancreatic tumorigenesis via neutrophil elastase from tumor-associated neutrophils[J].Gut Microbes,2022,14(1):2073785. [14]Jia W,Xie G,Jia W.Bile acid–microbiota crosstalk in gastrointestinal inflammation and carcinogenesis[J].Nature reviews Gastro- enterology&hepatology.2018,15(2):111-128 [15]Sarkar J,Aoki H,Wu R,et al.Conjugated bile acids accelerate progression of pancreatic cancer metastasis via S1PR2 signaling in cholestasis[J].Annals of Surgical Oncology,2023,30(3):1630-1641. [16]Yang C,Yuan H,Gu J,et al.ABCA8-mediated efflux of taurocholic acid contributes to gemcitabine insensitivity in human pancreatic cancer via the S1PR2-ERK pathway[J].Cell Death Discovery,2021,7(1):6. [17]Zhu S,Yang K,Yang S,et al.A high bile acid environment promotes apoptosis and inhibits migration in pancreatic cancer[J]. Bioengineered,2022,13(3):6719-6728. [18]Ren Z,Jiang J,Xie H,et al.Gut microbial profile analysis by MiSeq sequencing of pancreatic carcinoma patients in China[J].Oncotarget, 2017,8(56):95176. [19]Yin H,Pu N,Chen Q,et al.Gut-derived lipopolysaccharide remodels tumoral microenvironment and synergizes with PD-L1 checkpoint blockade via TLR4/MyD88/AKT/NF-κB pathway in pancreatic cancer[J].Cell Death&Disease,2021,12(11):1033. [20]Chandra V,Li L,Le Roux O,et al.Gut epithelial Interleukin-17 receptor A signaling can modulate distant tumors growth through microbial regulation[J].Cancer cell,2024,42(1):85-100.e6. [21]Jeong S H,Hurh K,Park E C,et al.Risk of Pancreatic Cancer After Acute Pancreatitis:A Retrospective Analysis of the Korean National Sample Cohort[J].Journal of Korean Medical Science,2024,39(4). [22]Takeuchi T,Kameyama K,Miyauchi E,et al.Fatty acid overproduction by gut commensal microbiota exacerbates obesity[J].Cell Metabolism,2023,35(2):361-375.e9. [23]国家卫生健康委员会医院管理研究所，中华医学会肠外肠内营养学分会肠道微生态协作组.肠道菌群移植临床应用管理中国专 家共识(2022 版)[J].中华胃肠外科杂志,2022,25(9):747-756.DOI:10.3760/cma.j.cn441530-20220725-00324. [24]Routy B,Le Chatelier E,Derosa L,et al.Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors[J].Science,2018,359(6371):91-97. [25]Baruch E N,Youngster I,Ben-Betzalel G,et al.Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients[J].Science,2021,371(6529):602-609. [26]Tintelnot J,Xu Y,Lesker T R,et al.Microbiota-derived 3-IAA influences chemotherapy efficacy in pancreatic cancer[J].Nature,2023, 615(7950):168-174. [27]Swanson K S,Gibson G R,Hutkins R,et al.The International Scientific Association for Probiotics and Prebiotics(ISAPP)consensus statement on the definition and scope of synbiotics[J].Nature Reviews Gastroenterology&Hepatology,2020,17(11):687-701. [28]Konishi H,Isozaki S,Kashima S,et al.Probiotic Aspergillus oryzae produces anti-tumor mediator and exerts anti-tumor effects in pancreatic cancer through the p38 MAPK signaling pathway[J].Scientific Reports,2021,11(1):11070. [29]Zhu Z,Yi B,Tang Z,et al.Lactobacillus casei combined with Lactobacillus reuteri alleviate pancreatic cancer by inhibiting TLR4 to promote macrophage M1 polarization and regulate gut microbial homeostasis[J].BMC cancer,2023,23(1):1044. [30]Panebianco C,Pisati F,Villani A,et al.Counteracting gemcitabine+nab-paclitaxel induced dysbiosis in KRAS wild type and KRASG12D mutated pancreatic cancer in vivo model[J].Cell Death Discovery,2023,9(1):116. [31]Chaib M,Hafeez B B,Mandil H,et al.Reprogramming of pancreatic adenocarcinoma immunosurveillance by a microbial probiotic siderophore[J].Communications Biology,2022,5(1):1181. [32]李金星,蒋丰岭,周青青等.合生元制剂对抗生素诱导肠道紊乱的改善作用[J].食品研究与开发,2022,43(3):28-3341 [33]Salminen S,Collado M C,Endo A,et al.The International Scientific Association of Probiotics and Prebiotics(ISAPP)consensus statement on the definition and scope of postbiotics[J].Nature Reviews Gastroenterology&Hepatology,2021,18(9):649-667. [34]Ubachs J,Ziemons J,Soons Z,et al.Gut microbiota and short-chain fatty acid alterations in cachectic cancer patients[J].J Cachexia Sarcopenia Muscle.2021,12(6):2007-2021. [35]Yang X,Zhang Z,Shen X,et al.Clostridium butyricum and its metabolite butyrate promote ferroptosis susceptibility in pancreatic ductal adenocarcinoma[J].Cellular Oncology,2023:1-14. [36]Panebianco C,Villani A,Pisati F,et al.Butyrate,a postbiotic of intestinal bacteria,affects pancreatic cancer and gemcitabine response in in vitro and in vivo models[J].Biomedicine&Pharmacotherapy,2022,151:113163. [37]Mirji G,Worth A,Bhat S A,et al.The microbiome-derived metabolite TMAO drives immune activation and boosts responses to immune checkpoint blockade in pancreatic cancer[J].Science immunology,2022,7(75):eabn0704.

点击下载PDF