TY - JOUR
T1 - Contributions of the Microbiome-Derived Metabolome for Risk Assessment and Prognostication of Pancreatic Cancer
AU - León-Letelier, Ricardo A.
AU - Dou, Rongzhang
AU - Vykoukal, Jody
AU - Yip-Schneider, Michele T.
AU - Maitra, Anirban
AU - Irajizad, Ehsan
AU - Wu, Ranran
AU - Dennison, Jennifer B.
AU - Do, Kim An
AU - Zhang, Jianjun
AU - Schmidt, C. Max
AU - Hanash, Samir
AU - Fahrmann, Johannes F.
N1 - Publisher Copyright:
© 2024 Association for Diagnostics & Laboratory Medicine. All rights reserved.
PY - 2024/1/1
Y1 - 2024/1/1
N2 - 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.
AB - 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.
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U2 - 10.1093/clinchem/hvad186
DO - 10.1093/clinchem/hvad186
M3 - Review article
C2 - 38175578
AN - SCOPUS:85181627187
SN - 0009-9147
VL - 70
SP - 102
EP - 115
JO - Clinical chemistry
JF - Clinical chemistry
IS - 1
ER -