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Record W3107061190 · doi:10.11575/prism/38403

Helminth Regulation of the Colonic Microbiome: Implications for the Control of Colitis

2020· dissertation· en· W3107061190 on OpenAlexfundno aff
Adam Shute

Bibliographic record

VenuePRISM (University of Calgary) · 2020
Typedissertation
Languageen
FieldMedicine
TopicClostridium difficile and Clostridium perfringens research
Canadian institutionsnot available
FundersNatural Sciences and Engineering Research Council of CanadaCanadian Association of Gastroenterology
KeywordsMicrobiomeColitisHelminthsGut microbiomeUlcerative colitisImmunologyMedicineBiologyBioinformaticsInternal medicineDisease

Abstract

fetched live from OpenAlex

The mammalian gut is a dynamic and complex organ composed of host cells, bacteria, fungi and viruses; while parasitic protozoa and helminths can be transient residents in the intestine. Through the advancements in high throughput sequencing, an increasing number of studies have catalogued taxonomic compositional changes in the gut microbiota following infection with parasitic helminths. However, the functional implications of such helminth-microbiota interactions on the host are not well understood, especially in the context of controlling inflammation. The McKay laboratory continuously demonstrates that mice infected with the rat tapeworm, Hymenolepis diminuta, are protected from dinitrobenzene sulfonic acid (DNBS)-induced colitis. My thesis seeks to determine if H. diminuta is dependent on the intestinal microbiota to protect from colonic inflammation and to determine the underlying mechanisms that are responsible for this anti-inflammatory event. Although H. diminuta does not require the microbiota to infect or be recognized/expelled by the murine host’s immune system, distinct compositional changes to the colonic microbiota occur during infection with H. diminuta. Removing microbes by using germ-free mice or disrupting the intestinal microbiota through broad-spectrum antibiotic use inhibits the anti-inflammatory mechanism of H. diminuta towards DNBS-colitis. In addition to characterizing the compositional shift in the intestinal microbiota of mice infected with H. diminuta, we demonstrated a significant increase in fecal short chain fatty acids (SCFA), in particular acetate and butyrate. Infecting free fatty receptor 2 (ffar2)-knockout mice with H. diminuta inhibited the beneficial effect towards DNBS, and in parallel to this, treating mice with neutralizing IL-10 antibodies also blocked the protective effect of H. diminuta when challenged with DNBS. Immunostaining for IL-10Rα demonstrated increased reactivity in colonic tissues of mice that were either treated with butyrate enemas or infected with H. diminuta, as compared to tissue from naive mice. The data in this thesis provides proof-of-principle evidence that H. diminuta modulates both the gut microbiota and the immune system of its host to protect from chemically induced colitis. Where the removal of these constituents, inhibits H. diminuta’s ability to protect the host from colitis.

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: Observational · Consensus signal: none
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 studies0.0000.001
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0010.001
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 head0.015
GPT teacher head0.252
Teacher spread0.237 · 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
Published2020
Admission routes1
Has abstractyes

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