Zhejiang Chinese Medical University, Hangzhou 310053, China.
Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310000, China.
Pharmacol Res. 2024 Oct;208:107364. doi: 10.1016/j.phrs.2024.107364. Epub 2024 Aug 22.
We delve into the critical role of the gut microbiota and its metabolites in the pathogenesis and progression of hepatobiliary and pancreatic (HBP) cancers, illuminating an urgent need for breakthroughs in diagnostic and therapeutic strategies. Given the high mortality rates associated with HBP cancers, which are attributed to aggressive recurrence, metastasis, and poor responses to chemotherapy, exploring microbiome research presents a promising frontier. This research highlights how microbial metabolites, including secondary bile acids, short-chain fatty acids, and lipopolysaccharides, crucially influence cancer cell behaviors such as proliferation, apoptosis, and immune evasion, significantly contributing to the oncogenesis and progression of HBP cancers. By integrating the latest findings, we discuss the association of microbial alterations with HBP cancers, key metabolites, and their implications, and how metabolomics and microbiomics can enhance diagnostic precision. Furthermore, the paper explores strategies for targeted therapies through microbiome metabolomics, including the direct therapeutic effects of microbiome metabolites and potential synergistic effects on conventional therapies. We also recognize that the field of microbial metabolites for the diagnosis and treatment of tumors still has a lot of problems to be solved. The aim of this study is to pioneer microbial metabolite research and provide a reference for HBP cancer diagnosis, treatment, and prognosis.
我们深入探讨了肠道微生物群及其代谢物在肝胆胰腺(HBP)癌症发病机制和进展中的关键作用,阐明了在诊断和治疗策略方面取得突破的迫切需要。鉴于 HBP 癌症相关的高死亡率归因于侵袭性复发、转移和对化疗的反应不佳,探索微生物组研究具有广阔的前景。这项研究强调了微生物代谢物(包括次级胆汁酸、短链脂肪酸和脂多糖)如何关键地影响癌细胞的行为,如增殖、凋亡和免疫逃逸,这对 HBP 癌症的发生和发展有重大影响。通过整合最新的发现,我们讨论了微生物变化与 HBP 癌症、关键代谢物及其影响的关联,以及代谢组学和微生物组学如何提高诊断精度。此外,本文还探讨了通过微生物组代谢组学进行靶向治疗的策略,包括微生物代谢物的直接治疗效果以及对常规治疗的潜在协同作用。我们还认识到,微生物代谢物在肿瘤诊断和治疗领域仍有许多问题需要解决。本研究的目的是开拓微生物代谢物的研究,并为 HBP 癌症的诊断、治疗和预后提供参考。