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Colon Cancer-Associated Fusobacterium nucleatum May Originate From the Oral Cavity and Reach Colon Tumors via the Circulatory System

Fusobacterium nucleatum is a common oral bacterium that is enriched in colorectal adenomas and adenocarcinomas (CRC). In humans, high fusobacterial CRC abundance is associated with chemoresistance and poor prognosis. In animal models, fusobacteria accelerate CRC progression. Targeting F. nucleatum m...

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Autores principales: Abed, Jawad, Maalouf, Naseem, Manson, Abigail L., Earl, Ashlee M., Parhi, Lishay, Emgård, Johanna E. M., Klutstein, Michael, Tayeb, Shay, Almogy, Gideon, Atlan, Karine A., Chaushu, Stella, Israeli, Eran, Mandelboim, Ofer, Garrett, Wendy S., Bachrach, Gilad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426652/
https://www.ncbi.nlm.nih.gov/pubmed/32850497
http://dx.doi.org/10.3389/fcimb.2020.00400
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author Abed, Jawad
Maalouf, Naseem
Manson, Abigail L.
Earl, Ashlee M.
Parhi, Lishay
Emgård, Johanna E. M.
Klutstein, Michael
Tayeb, Shay
Almogy, Gideon
Atlan, Karine A.
Chaushu, Stella
Israeli, Eran
Mandelboim, Ofer
Garrett, Wendy S.
Bachrach, Gilad
author_facet Abed, Jawad
Maalouf, Naseem
Manson, Abigail L.
Earl, Ashlee M.
Parhi, Lishay
Emgård, Johanna E. M.
Klutstein, Michael
Tayeb, Shay
Almogy, Gideon
Atlan, Karine A.
Chaushu, Stella
Israeli, Eran
Mandelboim, Ofer
Garrett, Wendy S.
Bachrach, Gilad
author_sort Abed, Jawad
collection PubMed
description Fusobacterium nucleatum is a common oral bacterium that is enriched in colorectal adenomas and adenocarcinomas (CRC). In humans, high fusobacterial CRC abundance is associated with chemoresistance and poor prognosis. In animal models, fusobacteria accelerate CRC progression. Targeting F. nucleatum may reduce fusobacteria cancer progression and therefore determining the origin of CRC F. nucleatum and the route by which it reaches colon tumors is of biologic and therapeutic importance. Arbitrarily primed PCR performed previously on matched same-patients CRC and saliva F. nucleatum isolates, suggested that CRC F. nucleatum may originate from the oral cavity. However, the origin of CRC fusobacteria as well as the route of their arrival to the tumor have not been well-established. Herein, we performed and analyzed whole genome sequencing of paired, same-patient oral, and CRC F. nucleatum isolates and confirmed that CRC-fusobacteria originate from the oral microbial reservoir. Oral fusobacteria may translocate to CRC by descending via the digestive tract or using the hematogenous route during frequent transient bacteremia caused by chewing, daily hygiene activities, or dental procedures. Using the orthotropic CT26 mouse model we previously showed that IV injected F. nucleatum colonize CRC. Here, we compared CRC colonization by gavage vs. intravenous inoculated F. nucleatum in the MC38 and CT26 mouse orthotropic CRC models. Under the tested conditions, hematogenous fusobacteria were more successful in CRC colonization than gavaged ones. Our results therefore provide evidence that the hematogenous route may be the preferred way by which oral fusobacteria reach colon tumors.
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spelling pubmed-74266522020-08-25 Colon Cancer-Associated Fusobacterium nucleatum May Originate From the Oral Cavity and Reach Colon Tumors via the Circulatory System Abed, Jawad Maalouf, Naseem Manson, Abigail L. Earl, Ashlee M. Parhi, Lishay Emgård, Johanna E. M. Klutstein, Michael Tayeb, Shay Almogy, Gideon Atlan, Karine A. Chaushu, Stella Israeli, Eran Mandelboim, Ofer Garrett, Wendy S. Bachrach, Gilad Front Cell Infect Microbiol Cellular and Infection Microbiology Fusobacterium nucleatum is a common oral bacterium that is enriched in colorectal adenomas and adenocarcinomas (CRC). In humans, high fusobacterial CRC abundance is associated with chemoresistance and poor prognosis. In animal models, fusobacteria accelerate CRC progression. Targeting F. nucleatum may reduce fusobacteria cancer progression and therefore determining the origin of CRC F. nucleatum and the route by which it reaches colon tumors is of biologic and therapeutic importance. Arbitrarily primed PCR performed previously on matched same-patients CRC and saliva F. nucleatum isolates, suggested that CRC F. nucleatum may originate from the oral cavity. However, the origin of CRC fusobacteria as well as the route of their arrival to the tumor have not been well-established. Herein, we performed and analyzed whole genome sequencing of paired, same-patient oral, and CRC F. nucleatum isolates and confirmed that CRC-fusobacteria originate from the oral microbial reservoir. Oral fusobacteria may translocate to CRC by descending via the digestive tract or using the hematogenous route during frequent transient bacteremia caused by chewing, daily hygiene activities, or dental procedures. Using the orthotropic CT26 mouse model we previously showed that IV injected F. nucleatum colonize CRC. Here, we compared CRC colonization by gavage vs. intravenous inoculated F. nucleatum in the MC38 and CT26 mouse orthotropic CRC models. Under the tested conditions, hematogenous fusobacteria were more successful in CRC colonization than gavaged ones. Our results therefore provide evidence that the hematogenous route may be the preferred way by which oral fusobacteria reach colon tumors. Frontiers Media S.A. 2020-08-07 /pmc/articles/PMC7426652/ /pubmed/32850497 http://dx.doi.org/10.3389/fcimb.2020.00400 Text en Copyright © 2020 Abed, Maalouf, Manson, Earl, Parhi, Emgård, Klutstein, Tayeb, Almogy, Atlan, Chaushu, Israeli, Mandelboim, Garrett and Bachrach. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Abed, Jawad
Maalouf, Naseem
Manson, Abigail L.
Earl, Ashlee M.
Parhi, Lishay
Emgård, Johanna E. M.
Klutstein, Michael
Tayeb, Shay
Almogy, Gideon
Atlan, Karine A.
Chaushu, Stella
Israeli, Eran
Mandelboim, Ofer
Garrett, Wendy S.
Bachrach, Gilad
Colon Cancer-Associated Fusobacterium nucleatum May Originate From the Oral Cavity and Reach Colon Tumors via the Circulatory System
title Colon Cancer-Associated Fusobacterium nucleatum May Originate From the Oral Cavity and Reach Colon Tumors via the Circulatory System
title_full Colon Cancer-Associated Fusobacterium nucleatum May Originate From the Oral Cavity and Reach Colon Tumors via the Circulatory System
title_fullStr Colon Cancer-Associated Fusobacterium nucleatum May Originate From the Oral Cavity and Reach Colon Tumors via the Circulatory System
title_full_unstemmed Colon Cancer-Associated Fusobacterium nucleatum May Originate From the Oral Cavity and Reach Colon Tumors via the Circulatory System
title_short Colon Cancer-Associated Fusobacterium nucleatum May Originate From the Oral Cavity and Reach Colon Tumors via the Circulatory System
title_sort colon cancer-associated fusobacterium nucleatum may originate from the oral cavity and reach colon tumors via the circulatory system
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426652/
https://www.ncbi.nlm.nih.gov/pubmed/32850497
http://dx.doi.org/10.3389/fcimb.2020.00400
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