Structure of the Mucosal and Stool Microbiome in Lynch Syndrome.
Adenoma
/ microbiology
Adult
Aged
Aged, 80 and over
Colectomy
/ adverse effects
Colonic Neoplasms
/ diagnosis
Colorectal Neoplasms, Hereditary Nonpolyposis
/ diagnosis
Feces
/ microbiology
Female
Gastrointestinal Microbiome
/ genetics
Humans
Male
Metagenomics
Middle Aged
Prospective Studies
RNA, Ribosomal, 16S
/ genetics
Transcriptome
Tumor Microenvironment
Lynch syndrome
colorectal cancer
human microbiome
metagenomics
metatranscriptomics
Journal
Cell host & microbe
ISSN: 1934-6069
Titre abrégé: Cell Host Microbe
Pays: United States
ID NLM: 101302316
Informations de publication
Date de publication:
08 04 2020
08 04 2020
Historique:
received:
09
04
2019
revised:
22
11
2019
accepted:
10
03
2020
pubmed:
3
4
2020
medline:
30
12
2020
entrez:
3
4
2020
Statut:
ppublish
Résumé
The gut microbiota has been associated with colorectal cancer (CRC), but causal alterations preceding CRC have not been elucidated. To prospectively assess microbiome changes prior to colorectal neoplasia, we investigated samples from 100 Lynch syndrome patients using 16S rRNA gene sequencing of colon biopsies, coupled with metagenomic and metatranscriptomic sequencing of feces. Colectomy and CRC history represented the largest effects on microbiome profiles. A subset of Clostridiaceae were depleted in stool corresponding with baseline adenomas, while Desulfovibrio was enriched both in stool and in mucosal biopsies. A classifier leveraging stool metatranscriptomes resulted in modest power to predict interval development of preneoplastic colonic adenoma. Predictive transcripts corresponded with a shift in flagellin contributors and oxidative metabolic microenvironment, potentially factors in local CRC pathogenesis. This suggests that the effectiveness of prospective microbiome monitoring for adenomas may be limited but supports the potential causality of these consistent, early microbial changes in colonic neoplasia.
Identifiants
pubmed: 32240601
pii: S1931-3128(20)30169-4
doi: 10.1016/j.chom.2020.03.005
pmc: PMC7453618
mid: NIHMS1615898
pii:
doi:
Substances chimiques
RNA, Ribosomal, 16S
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
585-600.e4Subventions
Organisme : NCI NIH HHS
ID : R01 CA202704
Pays : United States
Organisme : NCI NIH HHS
ID : L30 CA209764
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA154426
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009001
Pays : United States
Organisme : NIDDK NIH HHS
ID : K01 DK120742
Pays : United States
Organisme : Cancer Research UK
Pays : United Kingdom
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests C.H. is a member of the Seres Therapeutics scientific advisory board. A.T.C is a Stuart and Suzanne Steele MGH Research Scholar.
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