Enrichment of Bacteroides fragilis and enterotoxigenic Bacteroides fragilis in CpG island methylator phenotype (CIMP)-high colorectal carcinoma.

DNA methylation Dysbiosis Epigenetics Microbiota Molecular pathological epidemiology Pathogen

Journal

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
ISSN: 1469-0691
Titre abrégé: Clin Microbiol Infect
Pays: England
ID NLM: 9516420

Informations de publication

Date de publication:
22 Jan 2024
Historique:
received: 12 10 2023
revised: 04 12 2023
accepted: 13 01 2024
medline: 25 1 2024
pubmed: 25 1 2024
entrez: 24 1 2024
Statut: aheadofprint

Résumé

Data support that enterotoxigenic Bacteroides fragilis (ETBF) harbouring the Bacteroides fragilis toxin (bft) gene may promote colorectal tumourigenesis through the serrated neoplasia pathway. We hypothesised that ETBF may be enriched in colorectal carcinoma subtypes with high-level CpG island methylator phenotype (CIMP-high), BRAF mutation, and high-level microsatellite instability (MSI-high). Quantitative polymerase chain reaction assays were designed to quantify DNA amounts of Bacteroides fragilis, ETBF, and each bft gene isotype (bft-1, bft-2, or bft-3) in colorectal carcinomas in the Health Professionals Follow-up Study and Nurses' Health Study. We used multivariable-adjusted logistic regression models with the inverse probability weighting method. We documented 4,476 colorectal cancer cases, including 1,232 cases with available bacterial data. High DNA amounts of Bacteroides fragilis and ETBF were positively associated with BRAF mutation (P ≤0.0003), CIMP-high (P ≤0.0002), and MSI-high (P <0.0001 and P =0.01, respectively). Multivariable-adjusted odds ratios (ORs, with 95% confidence interval) for high Bacteroides fragilis were 1.40 (1.06-1.85) for CIMP-high and 2.14 (1.65-2.77) for MSI-high, but 1.02 (0.78-1.35) for BRAF mutation. Multivariable-adjusted ORs for high ETBF were 2.00 (1.16-3.45) for CIMP-high and 2.86 (1.64-5.00) for BRAF mutation, but 1.09 (0.67-1.76) for MSI-high. Neither Bacteroides fragilis nor ETBF was associated with colorectal cancer-specific or overall survival. The tissue abundance of Bacteroides fragilis is associated with CIMP-high and MSI-high, whereas ETBF abundance is associated with CIMP-high and BRAF mutation in colorectal carcinoma. Our findings support the aetiological relevance of Bacteroides fragilis and ETBF in the serrated neoplasia pathway.

Identifiants

DOI: 10.1016/j.cmi.2024.01.013 PMID: 38266708
pubmed: 38266708
pii: S1198-743X(24)00034-X
doi: 10.1016/j.cmi.2024.01.013
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest C.L.S. has a grant from Janssen on enterotoxigenic Bacteroides fragilis. M.G. has the research funding of Janssen, Honorarium and AstraZeneca, and is advisory board of Chroma code. This study was not funded by any of these commercial entities.

Auteurs

Yasutoshi Takashima (Y)

Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, U.S; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, U.S.

Hidetaka Kawamura (H)

Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, U.S.

Kazuo Okadome (K)

Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, U.S.

Satoko Ugai (S)

Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, U.S; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, U.S.

Koichiro Haruki (K)

Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, U.S.

Kota Arima (K)

Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, U.S.

Kosuke Mima (K)

Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, U.S.

Naohiko Akimoto (N)

Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, U.S.

Jonathan A Nowak (JA)

Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, U.S; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, U.S.

Marios Giannakis (M)

Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, U.S; Broad Institute of MIT and Harvard, Cambridge, Massachusetts, U.S; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, U.S.

Wendy S Garrett (WS)

Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, U.S; Broad Institute of MIT and Harvard, Cambridge, Massachusetts, U.S.

Cynthia L Sears (CL)

Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.

Mingyang Song (M)

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, U.S; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, U.S; Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, U.S.

Tomotaka Ugai (T)

Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, U.S; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, U.S.

Shuji Ogino (S)

Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, U.S; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, U.S; Broad Institute of MIT and Harvard, Cambridge, Massachusetts, U.S; Cancer Immunology Program, Dana-Farber Harvard Cancer Centre, Boston, Massachusetts, U.S. Electronic address: sogino@bwh.harvard.edu.

Classifications MeSH