A45 ASSESSING THE ROLE OF MICROBIOTA DYSBIOSIS ON INTESTINAL TUFT CELL FUNCTIONS UPON <i>GIARDIA</i> INFECTION
Bibliographic record
Abstract
Abstract Background Enteric tuft cells can detect and respond to intestinal parasitic infection by modulating host responses to aid parasite clearance, yet the extent of tuft cell functions upon other infections remains to be elucidated. Previous work in our lab showed that the enteric protozoan parasite Giardia induced tuft and goblet cell hyperplasia, yet Giardia colonization in Pou2f3-/- (tuft cell-deficient) mice was impaired. Not only can Giardia modulate the gut microbiota and lead to microbial dysbiosis, but the microbiota itself can influence Giardia colonization. Interestingly, certain microbiota-derived products can activate tuft cells in the gut. In this study, we investigated the role of microbiota dysbiosis in the crosstalk between Giardia and tuft cells. Aims We aim to explore the bidirectional effects between tuft cells and Giardia infection by investigating the role of 1) the host microbiota influenced by the presence or absence of tuft cells in altering Giardia infectivity, and 2) Giardia modified microbiota in contributing to tuft cell activity. Methods Fecal matter from 6–8-week-old C57Bl/6 and Pou2f3-/- mice were administered to polyethylene glycol (PEG) treated C57Bl/6 mice via oral gavage for 7 days, followed by gavage with 5x104Giardia muris trophozoites. Duodenal parasite burden was assessed 11 days after infection. Small intestinal (SI) microbiota was collected from 5–7-week-old C57Bl/6 and Pou2f3-/- mice following 11 days of G. muris infection and transplanted into PEG treated C57Bl/6 and Pou2f3-/- recipients. 11 days post-transfer, SI tuft and goblet cell hyperplasia was assessed in recipient mice by immunohistochemistry, and Dclk1, Atoh1, and Muc2 gene expression was quantified by RT-qPCR. Parameters of gut motility were evaluated. Results FMT with Pou2f3-/- mouse fecal matter prior to Giardia infection led to improved weight gain during infection compared to FMT from C57Bl/6 mice. Giardia modified microbiota (GMM) did not induce tuft or goblet cell hyperplasia 11 days after transfer. Jejunal Dclk1, Atoh1, and Muc2 were no different after GMM compared to control microbiota (CM) transfer. Ileal Atoh1 or Muc2 were upregulated in mice receiving GMM from C57Bl/6 or Pou2f3-/- mice, respectively. Intestinal transit time and stool water content was altered in mice which received GMM from Pou2f3-/- mice compared to CM. Conclusions The resident microbiota in tuft cell deficient mice may in part contribute to limiting Giardia infection. Giardia modified microbiota does not substantially contribute to tuft cell hyperplasia or related gene expression alterations at 11 days after microbiota transfer. The mechanistic contributors to tuft cell hyperplasia during Giardia infection and how a lack of tuft cells can lead to impaired colonization does not appear to be primarily driven by microbiota alterations and remains to be fully defined. Funding Agencies NSERC
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".