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Metagenomic analysis of gut microbiome reveals a dynamic change in Alistipes onderdonkii in the preclinical model of pancreatic cancer, suppressing its proliferation

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Abstract
Pancreatic cancer is a lethal cancer with aggressive and invasive characteristics. By the time it is diagnosed, patients already have tumors extended to other organs and show extremely low survival rates. The gut microbiome is known to be associated with many diseases and its imbalance affects the pathogenesis of pancreatic cancer. In this study, we established an orthotopic, patient-derived xenograft model to identify how the gut microbiome is linked to pancreatic ductal adenocarcinoma (PDAC). Using the 16S rDNA metagenomic sequencing, we revealed that the levels of Alistipes onderdonkii and Roseburia hominis decreased in the gut microbiome of the PDAC model. To explore the crosstalk between the two bacteria and PDAC cells, we collected the supernatant of the bacteria or cancer cell culture medium and treated it in a cross manner. While the cancer cell medium did not affect bacterial growth, we observed that the A. onderdonkii medium suppressed the growth of the pancreatic primary cancer cells. Using the bromodeoxyuridine/7-amino-actinomycin D (BrdU/7-AAD) staining assay, we confirmed that the A. onderdonkii medium inhibited the proliferation of the pancreatic primary cancer cells. Furthermore, RNA-seq analysis revealed that the A. onderdonkii medium induced unique transcriptomic alterations in the PDAC cells, compared to the normal pancreatic cells. Altogether, our data suggest that the reduction in the A. onderdonkii in the gut microbiome provides a proliferation advantage to the pancreatic cancer cells.
Author(s)
김명지김시내안세희이기학오효재강민수김선원장수환
Issued Date
2021
Type
Article
Keyword
A. onderdonkiiGut microbeMetagenome analysisPDACPreclinical model
DOI
10.1007/s00253-021-11617-z
URI
https://oak.ulsan.ac.kr/handle/2021.oak/7324
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_proquest_miscellaneous_2582112652&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,Metagenomic%20analysis%20of%20gut%20microbiome%20reveals%20a%20dynamic%20change%20in%20Alistipes%20onderdonkii%20in%20the%20preclinical%20model%20of%20pancreatic%20cancer,%20suppressing%20its%20proliferation&offset=0&pcAvailability=true
Publisher
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
Location
미국
Language
영어
ISSN
0175-7598
Citation Volume
105
Citation Number
21
Citation Start Page
8343
Citation End Page
8358
Appears in Collections:
Medicine > Medicine
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