Dataset Information

Contributions of the Microbiome-Derived Metabolome for Risk Assessment and Prognostication of Pancreatic Cancer

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.

INSTRUMENT(S): Liquid Chromatography MS - positive - hilic, Liquid Chromatography MS - positive - reverse phase

SUBMITTER: Yining Cai

PROVIDER: MTBLS7260 | MetaboLights | 2023-08-09

REPOSITORIES: MetaboLights

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Dataset's files

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			Action	DRS
	MTBLS7260	Other
	FILES	Other
	a_MTBLS7260_LC-MS_positive_hilic_Biogenic_Amines_metabolite_profiling.txt	Txt
	a_MTBLS7260_LC-MS_positive_reverse-phase_Lipids_metabolite_profiling.txt	Txt
	a_MTBLS7260_LC-MS_positive_reverse-phase_Primary_Metabolites_metabolite_profiling.txt	Txt

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Publications

Contributions of the Microbiome-Derived Metabolome for Risk Assessment and Prognostication of Pancreatic Cancer.

León-Letelier Ricardo A RA Dou Rongzhang R Vykoukal Jody J Yip-Schneider Michele T MT Maitra Anirban A Irajizad Ehsan E Wu Ranran R Dennison Jennifer B JB Do Kim-An KA Zhang Jianjun J Schmidt C Max CM Hanash Samir S Fahrmann Johannes F JF

Clinical chemistry 20240101 1

<h4>Background</h4>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 ...[more]

PMID: 38175578

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Project description:Pancreatic cancer is the 3rd most prevalent cause of cancer related deaths in United states alone, with over 55000 patients being diagnosed in 2019 alone and nearly as many succumbing to it. Late detection, lack of effective therapy and poor understanding of pancreatic cancer systemically contributes to its poor survival statistics. Obesity and high caloric intake linked co-morbidities like type 2 diabetes (T2D) have been attributed as being risk factors for a number of cancers including pancreatic cancer. Studies on gut microbiome has shown that lifestyle factors as well as diet has a huge effect on the microbial flora of the gut. Further, modulation of gut microbiome has been seen to contribute to effects of intensive insulin therapy in mice on high fat diet. In another study, abnormal gut microbiota was reported to contribute to development of diabetes in Db/Db mice. Recent studies indicate that microbiome and microbial dysbiosis plays a role in not only the onset of disease but also in its outcome. In colorectal cancer, Fusobacterium has been reported to promote therapy resistance. Certain intra-tumoral bacteria have also been shown to elicit chemo-resistance by metabolizing anti-cancerous agents. In pancreatic cancer, studies on altered gut microbiome have been relatively recent. Microbial dysbiosis has been observed to be associated with pancreatic tumor progression. Modulation of microbiome has been shown to affect response to anti-PD1 therapy in this disease as well. However, most of the studies in pancreatic cancer and microbiome have remained focused om immune modulation. In the current study, we observed that in a T2D mouse model, the microbiome changed significantly as the hyperglycemia developed in these animals. Our results further showed that, tumors implanted in the T2D mice responded poorly to Gemcitabine/Paclitaxel (Gem/Pac) standard of care compared to those in the control group. A metabolomic reconstruction of the WGS of the gut microbiota further revealed that an enrichment of bacterial population involved in drug metabolism in the T2D group.