Evidence map›Paper›PMID 38689063›Full record

ArticleNature medicine2024

Microbiome confounders and quantitative profiling challenge predicted microbial targets in colorectal cancer development.

Raúl Y Tito, Sara Verbandt, Marta Aguirre Vazquez, Leo Lahti, Chloe Verspecht, Verónica Lloréns-Rico, Sara Vieira-Silva, Janine Arts, Gwen Falony, Evelien Dekker and 3 more

Abstract read
In one paragraph

Article in Nature medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
96citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

96 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  11. Article
  12. Emerging trends in the global burden of colorectal cancer.Nature reviews. Clinical oncology · 2026
    Review
  13. Dissecting the Ecological Structure of Health and Disease in the Global Gut Microbiome.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. Harnessing the microbiome for cancer therapy.Nature reviews. Microbiology · 2026
    Review

36 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Raúl Y Tito *Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute, Katholieke Universiteit Leuven, Leuven, Belgium.ORCID 0000-0001-9660-7621
Sara Verbandt *Digestive Oncology, Department of Oncology, Katholieke Universiteit Leuven, Leuven, Belgium.
Marta Aguirre VazquezDigestive Oncology, Department of Oncology, Katholieke Universiteit Leuven, Leuven, Belgium.
Leo LahtiLaboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute, Katholieke Universiteit Leuven, Leuven, Belgium.ORCID 0000-0001-5537-637X
Chloe VerspechtLaboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute, Katholieke Universiteit Leuven, Leuven, Belgium.
Verónica Lloréns-RicoLaboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute, Katholieke Universiteit Leuven, Leuven, Belgium.
Sara Vieira-SilvaLaboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute, Katholieke Universiteit Leuven, Leuven, Belgium.ORCID 0000-0002-4616-7602
Janine ArtsOncology, Janssen Pharmaceutica NV, Beerse, Belgium.
Gwen FalonyLaboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute, Katholieke Universiteit Leuven, Leuven, Belgium.
Evelien DekkerDepartment of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
Joke ReumersTherapeutics Discovery, Janssen Pharmaceutica NV, Beerse, Belgium.ORCID 0000-0001-5434-6515
Sabine Tejpar *Digestive Oncology, Department of Oncology, Katholieke Universiteit Leuven, Leuven, Belgium.ORCID 0000-0003-3281-8643
Jeroen Raes *Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute, Katholieke Universiteit Leuven, Leuven, Belgium. jeroen.raes@kuleuven.be.ORCID 0000-0002-1337-041X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Despite substantial progress in cancer microbiome research, recognized confounders and advances in absolute microbiome quantification remain underused; this raises concerns regarding potential spurious associations. Here we study the fecal microbiota of 589 patients at different colorectal cancer (CRC) stages and compare observations with up to 15 published studies (4,439 patients and controls total). Using quantitative microbiome profiling based on 16S ribosomal RNA amplicon sequencing, combined with rigorous confounder control, we identified transit time, fecal calprotectin (intestinal inflammation) and body mass index as primary microbial covariates, superseding variance explained by CRC diagnostic groups. Well-established microbiome CRC targets, such as Fusobacterium nucleatum, did not significantly associate with CRC diagnostic groups (healthy, adenoma and carcinoma) when controlling for these covariates. In contrast, the associations of Anaerococcus vaginalis, Dialister pneumosintes, Parvimonas micra, Peptostreptococcus anaerobius, Porphyromonas asaccharolytica and Prevotella intermedia remained robust, highlighting their future target potential. Finally, control individuals (age 22-80 years, mean 57.7 years, standard deviation 11.3) meeting criteria for colonoscopy (for example, through a positive fecal immunochemical test) but without colonic lesions are enriched for the dysbiotic Bacteroides2 enterotype, emphasizing uncertainties in defining healthy controls in cancer microbiome research. Together, these results indicate the importance of quantitative microbiome profiling and covariate control for biomarker identification in CRC microbiome studies.

Indexed as

Colorectal NeoplasmsFecesGastrointestinal MicrobiomeRNA, Ribosomal, 16SAdultAgedAged, 80 and overFemaleHumansLeukocyte L1 Antigen ComplexMaleMicrobiotaMiddle AgedYoung AdultLeukocyte L1 Antigen ComplexRNA, Ribosomal, 16S

Identifiers

PMID38689063
PMCPMC11108775

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.