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Record W4220933445 · doi:10.21203/rs.3.rs-1475049/v1

Mucin foraging enables Akkermansia muciniphila to compete against other microbes in the gut and to modulate host sterol biosynthesis

2022· preprint· en· W4220933445 on OpenAlexfundno aff
Lauren Davey, Per Malkus, Max M. Villa, Lee Dolat, Zachary Holmes, Jeffrey Letourneau, Eduard Ansaldo, Lawrence A. David, Greg Barton, Raphael H. Valdivia

Bibliographic record

VenueResearch Square · 2022
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenomics and Phylogenetic Studies
Canadian institutionsnot available
FundersNatural Sciences and Engineering Research Council of CanadaNational Institutes of HealthAmerican Heart Association
KeywordsAkkermansia muciniphilaMucinHost (biology)SterolBiologyForagingMicrobiologyBiosynthesisEcologyBiochemistryGut floraCholesterolEnzyme

Abstract

fetched live from OpenAlex

Abstract Akkermansia muciniphila, a prominent member of the gastrointestinal tract (GI) microbiota, uses mucins as a sole source of carbon and nitrogen. A. muciniphila is considered a next-generation probiotic because its abundance in humans positively correlates with protection from metabolic syndrome and obesity. However, A. muciniphila is intractable to genetic analysis and thus the molecular mechanisms underlying the metabolism of mucin, its colonization of the GI tract, and its impact on host physiology are poorly understood. Here, we developed and applied transposon mutagenesis to identify A. muciniphila factors important for the use of mucin and determined that mucin degradation products accumulate in internal compartments through a process that requires pili and a periplasmic protein complex. We further determined that the degradation of mucin and related proteoglycans is important for colonization of the GI by A. muciniphila but only in the context of competing microbes. In germ free mice, mucin use by A. muciniphila repressed the expression of host genes required for mevalonate and cholesterol biosynthesis in the colon, providing a molecular link between A. muciniphila metabolism of mucins, the regulation of lipid homeostasis and potential probiotic activities.

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 score0.001
Threshold uncertainty score0.004

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 science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.041
GPT teacher head0.338
Teacher spread0.297 · 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

Citations3
Published2022
Admission routes1
Has abstractyes

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