Evidence map›Paper›PMID 38266708›Full record

ArticleClinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases2024

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

Yasutoshi Takashima, Hidetaka Kawamura, Kazuo Okadome, Satoko Ugai, Koichiro Haruki, Kota Arima, Kosuke Mima, Naohiko Akimoto, Jonathan A Nowak, Marios Giannakis and 5 more

Open access · bronzeAbstract read
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In one paragraph

Article in Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
4.0field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 14 citations in OpenAlex.

  1. Review
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  8. Intestinal dysbiosis and colorectal cancer.Chinese medical journal · 2025
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 4 institutions in 1 country.

Yasutoshi TakashimaProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Hidetaka KawamuraProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
Kazuo OkadomeProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
Satoko UgaiProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Koichiro HarukiProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
Kota ArimaProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
Kosuke MimaProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
Naohiko AkimotoProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
Jonathan A NowakProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Marios GiannakisDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Wendy S GarrettDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Cynthia L SearsDivision of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Mingyang SongDepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA.
Tomotaka UgaiProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Shuji OginoProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Cancer Immunology Program, Dana-Farber Harvard Cancer Centre, Boston, MA, USA. Electronic address: sogino@bwh.harvard.edu.
Harvard University · USBrigham and Women's Hospital · USBloomberg (United States) · USBroad Institute · US

Funding

Statistical MethodsP01CA087969 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ELIASSEN, A. HEATHER, TAMIMI, RULLA M · 2000 to 2019
$77.8M
Validity of Diet and Activity Measures in WomenP01CA055075 · NCI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI FUCHS, CHARLES S · 1991 to 2009
$41.8M
Long Term Multidisciplinary Study of Cancer in Women: The Nurses Health StudyUM1CA186107 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ELIASSEN, A. HEATHER, STAMPFER, MEIR · 2014 to 2023
$22.3M
Cancer Epidemiology Cohort in Male Health ProfessionalsU01CA167552 · NCI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Lorelei Mucci, Walter C. Willett · 2017 to 2026
$17.0M
Cancer Epidemiology Cohort in Male Health ProfessionalsUM1CA167552 · NCI · HARVARD SCHOOL OF PUBLIC HEALTH · PI WILLETT, WALTER C. · 2012 to 2016
$11.5M
Accelerating Transdisciplinary Epidemiology of Colorectal CancerR35CA197735 · NCI · DANA-FARBER CANCER INST · PI OGINO, SHUJI · 2015 to 2021
$6.0M
Coffee and metabolites modulating the gut microbiome for improved colorectal cancer survivalR01CA263776 · NCI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Mingyang Song · 2022 to 2026
$3.3M
The Gut Microbiome, Lifestyle, and Colorectal NeoplasiaU01CA261961 · NCI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Mingyang Song · 2022 to 2026
$3.0M
Epigenetic Events and Colorectal Cancer EpidemiologyR01CA151993 · NCI · DANA-FARBER CANCER INST · PI OGINO, SHUJI · 2010 to 2014
$2.6M
Integration of Immunology and Microbiology into Molecular Pathological Epidemiology of Colorectal CancerR50CA274122 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI UGAI, TOMOTAKA · 2023 to 2025
$506k
Integrating diet, lifestyle and tumor tissue molecular subtyping to study the role of adolescent calcium intake on the risk of early onset colorectal neoplasiaR21CA230873 · NCI · HARVARD SCHOOL OF PUBLIC HEALTH · PI OGINO, SHUJI, WU, KANA · 2018 to 2019
$427k
Cancer Research UK 27140NCI NIH HHS P01 CA055075NCI NIH HHS P01 CA087969NCI NIH HHS R01 CA151993NCI NIH HHS R01 CA263776NCI NIH HHS R21 CA230873NCI NIH HHS R35 CA197735NCI NIH HHS R50 CA274122NCI NIH HHS U01 CA167552NCI NIH HHS U01 CA261961NCI NIH HHS UM1 CA167552NCI NIH HHS UM1 CA186107
6 · The paper itself

Abstract

objectivesData support that enterotoxigenic Bacteroides fragilis (ETBF) harbouring the Bacteroides fragilis toxin (bft) gene may promote colorectal tumourigenesis through the serrated neoplasia pathway. We hypothesized 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).

methodsQuantitative PCR 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.

resultsWe documented 4476 colorectal cancer cases, including 1232 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 (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 odds ratios 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. DISCUSSION: 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.

Indexed as

Bacteroides fragilisColorectal NeoplasmsCpG IslandsDNA MethylationMetalloendopeptidasesAdultAgedBacterial ToxinsBacteroides InfectionsFemaleHumansMaleMicrosatellite InstabilityMiddle AgedMutationPhenotypeBacterial ToxinsBacteroides fragilis toxinBRAF protein, humanMetalloendopeptidasesProto-Oncogene Proteins B-rafDNA methylationDysbiosisEpigeneticsMicrobiotaMolecular pathological epidemiologyPathogen

Identifiers

PMID38266708
PMCPMC11043012
OpenAlexW4391089859

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.