A99 IMPACT OF OSMOTIC PERTURBATIONS ON THE GUT MICROBIOTA AND HOST HEALTH
Bibliographic record
Abstract
Abstract Background Osmotic diarrhea is a prevalent condition concurrent with diverse pathologies such as Crohn’s disease and is due to unabsorbed solutes in the gastrointestinal contents inhibiting normal water absorption. Osmotic laxatives such as polyethylene glycol (PEG) take advantage of this process to counteract constipation. However, short-term PEG treatment impacts the gut microbial community, and in humanized and conventional mice leads to disappearance of the abundant and prevalent bacterial family S24-7, while increasing the relative abundance of a related family, Bacteroidaceae. Excitingly, despite community re-equilibration over weeks, S24-7 is capable of superseding other bacterial members and reach its original levels when reintroduced into the environment. My central hypothesis is that the depletion of S24-7 during osmotic diarrhea is due to its deficiency of stress response pathways required to counteract increased osmolality. However, in the absence of this stress, S24-7 is capable of exploiting a unique interaction with the immune system to successfully recolonize. Aims To shed light on this, I will pursue the following two aims: Aim 1: Compare the growth, survival and expression profiles of S24-7 and B. thetaiotaomicron in a bi-colonized gnotobiotic mouse model before, during and after osmotic perturbation to identify candidate genes involved in response to osmotic perturbation. Aim 2: Identify changes in S24-7 gene expression during recolonization and evaluate the host immune response. Methods Gnotobiotic mice were first colonized with S24-7 and then B. thetaiotaomicron, treated with PEG for 6 days and monitored during recovery and recolonization for 20 days. Fecal pellets were used to quantify bacterial abundances via qPCR and bacterial gene expression analysis through metatranscriptomics. Mouse serum was used for ELISA immunoassays to compare adaptive immune responses through serum IgG as well as to quantify glycine betaine levels. Results During PEG treatment S24-7 became undetectable and recolonized to pre-treatment levels during recovery. Using genomic and metagenomic annotation we have identified that S24-7 isolates do not possess the glycine betaine transport system, which is present in B. thetaiotaomicron (Figure 1). B. thetaiotaomicron reduced host serum glycine betaine levels, unlike S24-7. In S24-7 mono-colonized mice, S24-7 specific serum IgG was not detectable. However, once mice were co-colonized with B. thetaiotaomicron, both S24-7 and B. thetaiotaomicron specific IgG is detected, identifying an interesting relationship between S24-7 and the adaptive immune system that may shed light on its unique recolonization. Conclusions By studying S24-7 sensitivity to osmotic stress and its robust colonization abilities we are shedding light on the mechanisms of microbiota response to perturbations that are commonly experienced by the human gut. Funding Agencies None
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 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) | 0.000 | 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) | 0.002 | 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".