Colorectal cancer-associated microbiota contributes to oncogenic epigenetic signatures.
Animals
Cohort Studies
Colorectal Neoplasms
/ genetics
DNA Methylation
Dysbiosis
/ genetics
Epigenesis, Genetic
Fecal Microbiota Transplantation
Feces
/ microbiology
Female
Gastrointestinal Microbiome
/ genetics
Gene Expression Regulation
Germ-Free Life
Humans
Intestinal Mucosa
/ metabolism
Male
Mice, Inbred C3H
Promoter Regions, Genetic
RNA, Ribosomal, 16S
biomarker
cancer
colon
gene methylation
microbiota
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
26 11 2019
26 11 2019
Historique:
pubmed:
13
11
2019
medline:
28
4
2020
entrez:
13
11
2019
Statut:
ppublish
Résumé
Sporadic colorectal cancer (CRC) is a result of complex interactions between the host and its environment. Environmental stressors act by causing host cell DNA alterations implicated in the onset of cancer. Here we investigate the stressor ability of CRC-associated gut dysbiosis as causal agent of host DNA alterations. The epigenetic nature of these alterations was investigated in humans and in mice. Germ-free mice receiving fecal samples from subjects with normal colonoscopy or from CRC patients were monitored for 7 or 14 wk. Aberrant crypt foci, luminal microbiota, and DNA alterations (colonic exome sequencing and methylation patterns) were monitored following human feces transfer. CRC-associated microbiota induced higher numbers of hypermethylated genes in murine colonic mucosa (vs. healthy controls' microbiota recipients). Several gene promoters including SFRP1,2,3, PENK, NPY, ALX4, SEPT9, and WIF1 promoters were found hypermethylated in CRC but not in normal tissues or effluents from fecal donors. In a pilot study (
Identifiants
pubmed: 31712445
pii: 1912129116
doi: 10.1073/pnas.1912129116
pmc: PMC6883805
doi:
Substances chimiques
RNA, Ribosomal, 16S
0
Banques de données
ClinicalTrials.gov
['NCT01270360']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
24285-24295Subventions
Organisme : NIAID NIH HHS
ID : R01 AI108682
Pays : United States
Déclaration de conflit d'intérêts
Competing interest statement: I.S. shares rights in 3 patents: EP B31120, EP2635705, and EP 2955232 A1 20151216 based on methods for diagnosing adenomas and/or colorectal cancer.
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