PMID- 37541802
OWN - NLM
STAT- MEDLINE
DCOM- 20230911
LR  - 20240102
IS  - 1424-3911 (Electronic)
IS  - 1424-3903 (Linking)
VI  - 23
IP  - 6
DP  - 2023 Sep
TI  - Dynamics of intestinal and intratumoral microbiome signatures in genetically 
      engineered mice and human pancreatic ductal adenocarcinoma.
PG  - 663-673
LID - S1424-3903(23)01602-2 [pii]
LID - 10.1016/j.pan.2023.07.008 [doi]
AB  - BACKGROUND: Emerging evidence has recently revealed a prominent role of the 
      microbiome in pancreatic ductal adenocarcinoma (PDAC). However, while most 
      observations were made in patients, mouse models still require a precise 
      characterization of their disease-related microbiome to employ them for 
      mechanistic and interventional preclinical studies. METHODS: To investigate the 
      fecal and tumoral microbiome of LSL-Kras(G12D/+);LSL-Trp53(R172H/+);Pdx-1-Cre 
      (KPC) and control (CTRL) mice, Oxford Nanopore sequencing was applied. Feces were 
      collected from 10 KPC mice and 10 CTRLs at 3 timepoints (6 weeks, 12 weeks, and 
      when tumor-bearing (KPC) or 6 months (CTRL), respectively). Metagenomic 
      sequencing was performed on feces DNA. KPC tumor and healthy pancreas DNA samples 
      were subjected to 16S rRNA gene sequencing. Bacterial marker components were 
      detected in KPC tumor tissue over time by fluorescence in situ hybridization 
      (FISH) and immunohistochemistry (IHC). RESULTS: Murine fecal samples showed a 
      significantly different microbiome compared to age-matched healthy CTRLs 
      regarding beta diversity (p = 0.001, R2 = 0.2-0.25 for Bray-Curtis). Adjusted 
      human PDAC classifiers predicted disease status from feces of KPC mice achieving 
      area under the receiver operating characteristic (AUROC) values of 80%. 
      Furthermore, KPC tumors harbored significantly more bacterial components than 
      healthy pancreas. Also the microbial composition differs significantly between 
      KPC tumors and healthy pancreas tissue (p = 0.042 for Bray-Curtis). Microbiota 
      found highly abundant in human PDAC samples were considerably more abundant in 
      KPC tumors as compared to healthy pancreas samples (p-value <0.001). CONCLUSION: 
      KPC fecal samples show similarities with the microbial composition of stool 
      samples from human PDAC patients.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Pfisterer, Nina
AU  - Pfisterer N
AD  - Department of Gastroenterology, Gastrointestinal Oncology and Endocrinology, 
      University Medical Center Goettingen, 37075, Goettingen, Germany; Clinical 
      Research Unit KFO5002, University Medical Center Goettingen, 37075, Goettingen, 
      Germany.
FAU - Ammer-Herrmenau, Christoph
AU  - Ammer-Herrmenau C
AD  - Department of Gastroenterology, Gastrointestinal Oncology and Endocrinology, 
      University Medical Center Goettingen, 37075, Goettingen, Germany; Clinical 
      Research Unit KFO5002, University Medical Center Goettingen, 37075, Goettingen, 
      Germany.
FAU - Antweiler, Kai
AU  - Antweiler K
AD  - Institute of Medical Statistics, University Medical Center Goettingen, 37073, 
      Goettingen, Germany.
FAU - Kuffer, Stefan
AU  - Kuffer S
AD  - Institute of Pathology, University Medical Center Goettingen, 37075, Goettingen, 
      Germany.
FAU - Ellenrieder, Volker
AU  - Ellenrieder V
AD  - Department of Gastroenterology, Gastrointestinal Oncology and Endocrinology, 
      University Medical Center Goettingen, 37075, Goettingen, Germany; Clinical 
      Research Unit KFO5002, University Medical Center Goettingen, 37075, Goettingen, 
      Germany.
FAU - Neesse, Albrecht
AU  - Neesse A
AD  - Department of Gastroenterology, Gastrointestinal Oncology and Endocrinology, 
      University Medical Center Goettingen, 37075, Goettingen, Germany; Clinical 
      Research Unit KFO5002, University Medical Center Goettingen, 37075, Goettingen, 
      Germany. Electronic address: albrecht.neesse@med.uni-goettingen.de.
LA  - eng
PT  - Journal Article
DEP - 20230731
PL  - Switzerland
TA  - Pancreatology
JT  - Pancreatology : official journal of the International Association of 
      Pancreatology (IAP) ... [et al.]
JID - 100966936
RN  - 0 (RNA, Ribosomal, 16S)
SB  - IM
MH  - Humans
MH  - Mice
MH  - Animals
MH  - In Situ Hybridization, Fluorescence
MH  - RNA, Ribosomal, 16S
MH  - *Pancreatic Neoplasms/genetics/pathology
MH  - *Carcinoma, Pancreatic Ductal/genetics/pathology
MH  - Disease Models, Animal
MH  - *Microbiota/genetics
OTO - NOTNLM
OT  - KPC mouse model
OT  - Microbiome
OT  - Oxford nanopore technologies
OT  - PDAC
OT  - Pancreatic ductal adenocarcinoma
COIS- Declaration of competing interest The authors declare no conflict of interests.
EDAT- 2023/08/05 05:42
MHDA- 2023/09/11 06:42
CRDT- 2023/08/04 21:53
PHST- 2023/04/27 00:00 [received]
PHST- 2023/07/24 00:00 [revised]
PHST- 2023/07/29 00:00 [accepted]
PHST- 2023/09/11 06:42 [medline]
PHST- 2023/08/05 05:42 [pubmed]
PHST- 2023/08/04 21:53 [entrez]
AID - S1424-3903(23)01602-2 [pii]
AID - 10.1016/j.pan.2023.07.008 [doi]
PST - ppublish
SO  - Pancreatology. 2023 Sep;23(6):663-673. doi: 10.1016/j.pan.2023.07.008. Epub 2023 
      Jul 31.