A264 ORAL IRON SUPPLEMENTATION SHAPES THE RECOVERY OF GUT THE MICROBIOTA AND PROMOTES CARCINOGENESIS IN THE APCMIN/+ MOUSE MODEL
Bibliographic record
Abstract
Abstract Background Colorectal cancer (CRC) induces anemia in a large proportion of patients and is usually treated with oral iron supplementation. Surgery, the main treatment for CRC, is routinely accompanied by prophylactic antibiotics to avoid infection. Moreover, the concomitance of oral iron supplementation and antibiotics treatment is highly prevalent in general population. However, the combined effect of antibiotics and high luminal iron concentration in the gut on the microbiota and intestinal homeostasis remains unknown. Purpose This study sought to identify possible deleterious effects of the recovery from antibiotics exposure of the gut microbiota under oral iron supplementation. Method In order to assess the effects of luminal iron on the recovery of the gut microbiota, WT mice were subjected to antibiotic treatment with different concentrations of dietary iron. Then, to explore potential deleterious effects of this setup on CRC promotion and progression mediated by the human CRC gut microbiota, CRC model ApcMin/+ mice were subjected to antibiotics prior to gavage with fecal samples from anemic CRC patients, then fed different concentrations of dietary iron. The composition of the gut microbiota and its recovery after these interventions were assessed in stool samples by 16S rRNA. Gut microbiota functions were inferred by using the PICRUSt2, and short chain fatty acid (SCFA) concentration in feces were assessed by liquid-chromatography mass spectrometry. CRC progression and promotion were assessed by tumour counts and immunohistochemistry. Result(s) Recovery from antibiotics under high luminal iron concentration shifted the gut microbiota toward a Bacteroidetes phylum-dominant composition. Three bacterial species characterized as CRC initiators were significantly more abundant. Nitrogen, pentose phosphate, cyanoamino acid metabolisms were higher after recovery under oral iron supplementation. Antibiotic exposure induced a long-term increase in SCFAs linked to gut inflammation, propionate and succinate. For mice under high luminal iron concentration, they showed a lack of recovery in baseline levels of butyrate, a SCFA that inhibits cancer cell proliferation in the gut. In addition, an increase in CRC burden and progression were found in ApcMin/+ mice receiving fecal sample from patients and oral iron supplementation. Conclusion(s) Gut microbiota recovery from antibiotic exposure under oral iron supplementation is frequent in CRC patients, but is also common in the general population. This study identifies possible deleterious effects of the concomitance of these two disruptive agents of the gut microbiota on the CRC progression. Please acknowledge all funding agencies by checking the applicable boxes below Other Please indicate your source of funding; NSERC, ICM Disclosure of Interest None Declared
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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) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".