Evidence map›Paper›PMID 29846515›Full record

ArticleCarcinogenesis2018

Intestinal microbiota enhances pancreatic carcinogenesis in preclinical models.

Ryan M Thomas, Raad Z Gharaibeh, Josee Gauthier, Mark Beveridge, Jillian L Pope, Maria V Guijarro, Qin Yu, Zhen He, Christina Ohland, Rachel Newsome and 7 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Carcinogenesis, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 159 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
159citing papers in PubMed, 2 pooled it
6.2field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

159 citing papers in PubMed, 2 syntheses or guidelines pooled it, 219 citations in OpenAlex.

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99 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 2 institutions in 1 country.

Ryan M ThomasDepartment of Surgery, University of Florida College of Medicine, Gainesville, FL, USA.
Raad Z GharaibehDepartment of Medicine, University of Florida College of Veterinary Medicine, Gainesville, FL, USA.
Josee GauthierDepartment of Medicine, University of Florida College of Veterinary Medicine, Gainesville, FL, USA.
Mark BeveridgeDepartment of Surgery, University of Florida College of Medicine, Gainesville, FL, USA.
Jillian L PopeDepartment of Medicine, University of Florida College of Veterinary Medicine, Gainesville, FL, USA.
Maria V GuijarroDepartment of Anatomy and Cell Biology, University of Florida College of Veterinary Medicine, Gainesville, FL, USA.
Qin YuDepartment of Medicine, University of Florida College of Veterinary Medicine, Gainesville, FL, USA.
Zhen HeDepartment of Medicine, University of Florida College of Veterinary Medicine, Gainesville, FL, USA.
Christina OhlandDepartment of Medicine, University of Florida College of Veterinary Medicine, Gainesville, FL, USA.
Rachel NewsomeDepartment of Medicine, University of Florida College of Veterinary Medicine, Gainesville, FL, USA.
Jose TrevinoDepartment of Surgery, University of Florida College of Medicine, Gainesville, FL, USA.
Steven J HughesDepartment of Surgery, University of Florida College of Medicine, Gainesville, FL, USA.
Mary ReinhardLaboratory of Comparative Pathology, University of Florida College of Veterinary Medicine, Gainesville, FL, USA.
Kathryn WingleeDepartment of Bioinformatics and Genomics, The University of North Carolina at Charlotte College of Computing and Informatics, Charlotte, NC, USA.
Anthony A FodorDepartment of Bioinformatics and Genomics, The University of North Carolina at Charlotte College of Computing and Informatics, Charlotte, NC, USA.
Maria Zajac-KayeDepartment of Anatomy and Cell Biology, University of Florida College of Veterinary Medicine, Gainesville, FL, USA.
Christian JobinDepartment of Medicine, University of Florida College of Veterinary Medicine, Gainesville, FL, USA.
University of Florida · USUniversity of North Carolina at Charlotte · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in the United States yet data are scant regarding host factors influencing pancreatic carcinogenesis. Increasing evidence support the role of the host microbiota in carcinogenesis but its role in PDAC is not well established. Herein, we report that antibiotic-mediated microbial depletion of KrasG12D/PTENlox/+ mice showed a decreased proportion of poorly differentiated tumors compared to microbiota-intact KrasG12D/PTENlox/+ mice. Subsequent 16S rRNA PCR showed that ~50% of KrasG12D/PTENlox/+ mice with PDAC harbored intrapancreatic bacteria. To determine if a similar observation in humans correlates with presence of PDAC, benign and malignant human pancreatic surgical specimens demonstrated a microbiota by 16S bacterial sequencing and culture confirmation. However, the microbial composition did not differentiate PDAC from non-PDAC tissue. Furthermore, murine pancreas did not naturally acquire a pancreatic microbiota, as germ-free mice transferred to specific pathogen-free housing failed to acquire intrapancreatic bacteria over time, which was not augmented by a murine model of colitis. Finally, antibiotic-mediated microbial depletion of Nod-SCID mice, compared to microbiota-intact, showed increased time to PDAC xenograft formation, smaller tumors, and attenuated growth. Interestingly, both xenograft cohorts were devoid of intratumoral bacteria by 16S rRNA PCR, suggesting that intrapancreatic/intratumoral microbiota is not the sole driver of PDAC acceleration. Xenografts from microbiota-intact mice demonstrated innate immune suppression by immunohistochemistry and differential regulation of oncogenic pathways as determined by RNA sequencing. Our work supports a long-distance role of the intestinal microbiota on PDAC progression and opens new research avenues regarding pancreatic carcinogenesis.

Indexed as

AdultAgedAnimalsAnti-Bacterial AgentsBacteriaCarcinogenesisCarcinoma, Pancreatic DuctalCell Line, TumorDisease ProgressionFemaleGastrointestinal MicrobiomeGerm-Free LifeHost Microbial InteractionsHumansIntestinesMaleAnti-Bacterial AgentsRNA, Ribosomal, 16S

Identifiers

PMID29846515
PMCPMC6067127
OpenAlexW2806666357

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.