Microbiome-Derived Metabolites Show Promise for Pancreatic Cancer Risk Assessment
Gut and oral microbial dysbiosis in the pancreas releases metabolites that potentiate inflammation and tumour development. Using LC-MS, the authors demonstrate that microbe-derived metabolites are detectable in pancreatic cystic fluid and are associated with malignant progression of intraductal papillary mucinous neoplasms. The review synthesises evidence that circulating microbial metabolite signatures could identify individuals at high risk of pancreatic ductal adenocarcinoma and predict treatment response, opening avenues for early interception.
The original study
Contributions of the Microbiome-Derived Metabolome for Risk Assessment and Prognostication of Pancreatic Cancer.
- Authors
- León-Letelier RA, Dou R, Vykoukal J, Yip-Schneider MT, Maitra A, Irajizad E, et al.
- Journal
- Clinical chemistry
- Type
- Review, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
- PMID
- 38175578
Original abstract
BACKGROUND: Increasing evidence implicates microbiome involvement in the development and progression of pancreatic ductal adenocarcinoma (PDAC). Studies suggest that reflux of gut or oral microbiota can lead to colonization in the pancreas, resulting in dysbiosis that culminates in release of microbial toxins and metabolites that potentiate an inflammatory response and increase susceptibility to PDAC. Moreover, microbe-derived metabolites can exert direct effector functions on precursors and cancer cells, as well as other cell types, to either promote or attenuate tumor development and modulate treatment response. CONTENT: The occurrence of microbial metabolites in biofluids thereby enables risk assessment and prognostication of PDAC, as well as having potential for design of interception strategies. In this review, we first highlight the relevance of the microbiome for progression of precancerous lesions in the pancreas and, using liquid chromatography-mass spectrometry, provide supporting evidence that microbe-derived metabolites manifest in pancreatic cystic fluid and are associated with malignant progression of intraductal papillary mucinous neoplasm(s). We secondly summarize the biomarker potential of microbe-derived metabolite signatures for (a) identifying individuals at high risk of developing or harboring PDAC and (b) predicting response to treatment and disease outcomes. SUMMARY: The microbiome-derived metabolome holds considerable promise for risk assessment and prognostication of PDAC.