MétaCan
Menu
← Back to cohort
Record W4296130015 · doi:10.1101/2022.09.09.22279675

BACTERIAL ONCOTRAITS BUT NOT BIOFILMS ARE ASSOCIATED WITH DYSPLASIA IN ULCERATIVE COLITIS

2022· preprint· en· W4296130015 on OpenAlexaff
Carlijn E. Bruggeling, Maarten te Groen, Daniel Garza, Famke van Heeckeren tot Overlaer, Joyce P.M. Krekels, Basma-Chick Sulaiman, Davy Karel, Athreyu Rulof, Anne R. Schaaphok, Daniël L. A. H. Hornikx, Irıs D. Nagtegaal, Bas E. Dutilh, Frank Hoentjen, Annemarie Boleij

Bibliographic record

VenuemedRxiv · 2022
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGut microbiota and health
Canadian institutionsUniversity of Alberta
FundersKWF KankerbestrijdingNederlandse Organisatie voor Wetenschappelijk OnderzoekDeutsche Forschungsgemeinschaft
KeywordsDysplasiaFecesGastroenterologyBiologyUlcerative colitisMicrobiologyInternal medicinePathologyMedicineDisease

Abstract

fetched live from OpenAlex

Abstract Biofilms are polymeric matrices containing bacteria that can express oncotraits and are frequently present in ulcerative colitis (UC). Oncotraits can impact colon epithelial cells directly and may increase dysplasia risk. This study aimed to determine (1) the association of oncotraits and longitudinal biofilm presence with dysplasia risk in UC, and (2) the relation of bacterial composition with biofilms and dysplasia risk. In this prospective cohort study, feces and left- and right-sided colonic biopsies were collected from 80 UC patients and 35 controls. Oncotraits (FadA of Fusobacterium , BFT of Bacteroides fragilis , Colibactin (ClbB) and Intimin (Eae) of Escherichia coli ) in fecal DNA were assessed with multiplex qPCR. Biopsies were analyzed for biofilms (n=873) with 16S rRNA fluorescent in situ hybridization and shotgun metagenomic sequencing (n=265), and ki67-immunohistochemistry for cell proliferation. Associations were determined with a regression (mixed) model. ClbB significantly associated with dysplasia in UC (aOR 7.16, (95%CI 1.75-29.28, p<0.01)), while FadA was inversely associated (aOR 0.23, (95%CI 0.06-0.83, p=0.03)). Patients with UC had a significantly lower Shannon diversity compared to controls (p=0.0009), as well as patients with a biofilm (p=0.015) independent of disease status. The order Fusobacteriales was significantly correlated with a decreased dysplasia risk only in right-sided colonic biopsies (p<0.01). Longitudinal biofilms were not significantly associated with dysplasia (aOR 1.45 (95% CI0.63-3.40, p=0.38)), however, biofilm-positive biopsies showed increased epithelial hypertrophy (p=0.025). Colibactin and FadA impact dysplasia risk in UC, in contrast to biofilms. These oncotraits are valuable targets for future risk classification and intervention studies. What is already known on this topic Bacterial biofilms sometimes contain bacteria with oncogenic traits (oncotraits) and have been associated with colon carcinogenesis in mice and humans. It is yet unknown whether biofilms and oncotraits are involved in early carcinogenesis and could be used as a risk factor for dysplasia in ulcerative colitis patients. What this study add Bacterial biofilms associated with lower bacterial diversity and epithelial cell hypertrophy, but did not predict dysplasia. Moreover, in agreement to piling evidence suggesting a role of colibactin in human colorectal cancer, we provide the missing clinical evidence that this oncotrait actually associates with risk for (early) carcinogenesis in human patients. Additionally, dysplasia in UC patients was predicted by absence of Fusobacterium adhesin. How this study might affect research, practice or policy This prospective cohort study indicates a putative role of bacterial oncotraits in early carcinogenesis, suggesting them as promising targets for future risk classification and intervention studies in ulcerative colitis patients. Lay summary Patients with ulcerative colitis have an increased risk for colorectal cancer. This study found that bacterial factors in fecal material can predict the development of cancer precursors in these patients. Abstract Figure

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.017
GPT teacher head0.262
Teacher spread0.245 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2022
Admission routes1
Has abstractyes

Explore more

Same venuemedRxiv→Same topicGut microbiota and health→French-language works237,207→