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Record W4284992148 · doi:10.1101/2022.07.08.499212

Virus Infection Causes Dysbiosis to Promote Type 1 Diabetes Onset

2022· preprint· en· W4284992148 on OpenAlexaff
Zachary J. Morse, Rachel L. Simister, Sean A. Crowe, Marc S. Horwitz, Lisa C. Osborne

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2022
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicDiabetes and associated disorders
Canadian institutionsUniversity of British Columbia
Fundersnot available
KeywordsCoxsackievirusMicrobiomeImmunologyNodType 1 diabetesBiologyDysbiosisNOD miceAutoimmunityEnterovirusDiabetes mellitusImmune systemGut floraVirusEndocrinologyBioinformatics

Abstract

fetched live from OpenAlex

Abstract Autoimmune disorders like type 1 diabetes (T1D) are complex diseases caused by numerous factors including both genetic variance and environmental influences. Two such exogenous factors, intestinal microbial composition and enterovirus infection, have been independently associated with T1D onset in both humans and animal models. Since environmental factors rarely work in isolation, we examined the cross-talk between the microbiome and Coxsackievirus B4 (CVB4), an enterovirus that accelerates T1D onset in non-obese diabetic (NOD) mice. We demonstrate that CVB4-infection induced restructuring of the intestinal microbiome prior to T1D onset that was associated with thinning of the mucosal barrier, bacterial translocation to the pancreatic lymph node, and increased detection of circulating and intestinal commensal-reactive antibodies. Notably, the CVB4-induced change in community composition was strikingly similar to that of uninfected NOD mice that spontaneously developed diabetes, thus implying a mutual “diabetogenic” microbiome. Furthermore, fecal microbiome transfer (FMT) of the diabetogenic microbiota from CVB4-infected mice was sufficient to enhance T1D susceptibility in naïve NOD recipients. These findings support a model whereby CVB infection disrupts the microbiome and intestinal homeostasis in a way that promotes activation of autoreactive immune cells and T1D.

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)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0030.001

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 head0.009
GPT teacher head0.222
Teacher spread0.213 · 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 designBench or experimental
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 venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicDiabetes and associated disorders→French-language works237,207→