A43 MECHANISMS OF UNIQUE COLONIZATION DYNAMICS AND IMMUNE RESPONSES TO MURIBACULACEAE
Bibliographic record
Abstract
Abstract Background Commercially available probiotics have a limited ability to alter the gut microbiome and establish within a pre-existing microbial community. Increases in osmolality, a condition prevalent in intestinal diseases, depletes the highly abundant bacterial family Muribaculaceae (Mb) from the gut microbiome in a mouse model of short-term osmotic laxative use. Excitingly, despite microbial community re-equilibration in its absence, Mb supersedes other bacterial colonizers to its original abundance if reintroduced, suggesting unique colonization attributes and a potential privileged immune interaction. Aims We aimed to investigate whether and how Mb colonization affects intestinal innate and adaptive immune homeostasis, including the generation of Mb-specific antibodies. Methods To examine interactions between Mb and the immune system that allows for efficient colonization, we used the osmotic laxative polyethylene glycol (PEG) to clear Mb and then generated mice with complex microbiomes that either lack Mb completely (Mb naïve) or were introduced to 8 murine-derived Mb strains (Mb+). The same strains were then introduced to Mb naïve mice (primary exposure to the immune system). To model secondary exposure, Mb+ mice were treated with PEG, and Mb re-introduced 3 weeks later. Leukocytes from the small and large intestinal lamina propria and gut-draining mesenteric lymph nodes (mLNs) were profiled over 21 days to characterize colonization and recolonization dynamics. Results High-throughput 16SrRNA sequencing showed no significant difference between relative abundance of Mb isolates during colonization or recolonization, indicating that Mb is capable of establishing in mice that have never been colonized with it before, making up to 20% of the relative abundance. Broad immunophenotyping demonstrated robust CD11b-CD103+ dendritic cell and Germinal Centre B cell responses in the mLNs of mice seeing Mb for the first time, yet no subsequent plasmablast accumulation in the mLN or lamina propria. We also observed significantly increased type two innate lymphoid cells in the small intestine upon primary exposure to Mb. Recolonization elicited no detectable changes in the monitored populations. Conclusions The lack of immune reactivity upon reintroduction to Mb suggests Mb may evade immune detection upon repeat exposure and contribute to its robust colonization abilities. Determining mechanisms involved in Mb colonization and its impact on host immune responses could increase our understanding of colonization dynamics and highlights the potential of Mb as a model for microbiota reintroduction in therapeutic applications. Funding Agencies Weston Family Foundation
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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 | 0.000 |
| 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".