Mechanisms underlying gut dysfunction in a murine model of chronic parasitic infection
Bibliographic record
Abstract
Irritable bowel syndrome (IBS) is common in countries where chronic parasitic infestations are endemic. However, the relationship between parasitic infection and IBS is not clear. The aim of this study was to examine whether chronic parasitic infection is accompanied by gut dysfunction and whether the continued presence of the parasite is required for the maintenance of the dysfunction. We used chronic Trichuris muris infection in Th1-biased susceptible AKR mice to evaluate this relationship. AKR mice were infected with T. muris and were euthanized on various days postinfection (pi) to examine worm burden, muscle function, and immune and inflammatory responses. Mice were treated with the anthelmintic oxantel pamoate to assess the effect of eradication of infection on muscle function. Infection resulted in persistence of the parasite, elevated IFN-γ, and increased MPO activity evident at 45 days pi. This was accompanied by a reduction in muscle contractility and excitatory innervation. Whereas parasite eradication at 7 days pi normalized IFN-γ and muscle contractility, eradication at 28 days pi failed to normalize muscle contractility. Administration of dexamethasone after parasite eradication normalized all parameters. Anthelmintic treatment improved histology except for eosinophils, which were normalized by subsequent dexamethasone therapy. Persistent gut dysfunction is independent of the continued presence of the parasite and is maintained by inflammatory process that includes eosinophils. Thus data in this preclinical model suggest that parasitic infection could be a cause of IBS, and the lack of symptomatic improvement following eradication is insufficient evidence to refute a causal relationship between the infection and IBS.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".