Guo Xuanchi, Shao Yuhan
School of Stomatology, Shandong University, No. 44-1 Wenhua West Road, Jinan City, Shandong Province, China.
State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
Mol Med. 2025 Mar 18;31(1):103. doi: 10.1186/s10020-025-01166-w.
Pancreatic cancer, one of the most lethal malignancies, remains challenging due to late diagnosis, aggressive progression, and therapeutic resistance. Recent advances have revealed the presence of intratumoral microbiota, predominantly originating from the oral and gut microbiomes, which play pivotal roles in pancreatic cancer pathogenesis. The dynamic interplay between oral and gut microbial communities, termed the "oral-gut microbiota axis," contributes multifacetedly to pancreatic ductal adenocarcinoma (PDAC). Microbial translocation via anatomical or circulatory routes establishes tumor-resident microbiota, driving oncogenesis through metabolic reprogramming, immune regulation, inhibition of apoptosis, chronic inflammation, and dysregulation of the cell cycle. Additionally, intratumoral microbiota promote chemoresistance and immune evasion, further complicating treatment outcomes. Emerging evidence highlights microbial signatures in saliva and fecal samples as promising non-invasive diagnostic biomarkers, while microbial diversity correlates with prognosis. Therapeutic strategies targeting this axis-such as antibiotics, probiotics, and engineered bacteria-demonstrate potential to enhance treatment efficacy. By integrating mechanisms of microbial influence on tumor biology, drug resistance, and therapeutic applications, the oral-gut microbiota axis emerges as a critical regulator of PDAC, offering novel perspectives for early detection, prognostic assessment, and microbiome-based therapeutic interventions.
胰腺癌是最致命的恶性肿瘤之一，由于诊断延迟、进展迅速和治疗耐药性，仍然具有挑战性。最近的研究进展揭示了肿瘤内微生物群的存在，主要源自口腔和肠道微生物群，它们在胰腺癌的发病机制中起着关键作用。口腔和肠道微生物群落之间的动态相互作用，即“口腔-肠道微生物群轴”，对胰腺导管腺癌（PDAC）有多方面的影响。通过解剖学或循环途径的微生物易位建立了肿瘤驻留微生物群，通过代谢重编程、免疫调节、抑制细胞凋亡、慢性炎症和细胞周期失调来驱动肿瘤发生。此外，肿瘤内微生物群促进化疗耐药性和免疫逃逸，进一步使治疗结果复杂化。新出现的证据表明，唾液和粪便样本中的微生物特征有望成为有前景的非侵入性诊断生物标志物，而微生物多样性与预后相关。针对该轴的治疗策略，如抗生素、益生菌和工程菌，显示出提高治疗效果的潜力。通过整合微生物对肿瘤生物学、耐药性和治疗应用的影响机制，口腔-肠道微生物群轴成为PDAC的关键调节因子，为早期检测、预后评估和基于微生物群的治疗干预提供了新的视角。
