A173 LACK OF EXPERIMENTAL REPRODUCIBILITY IN PRECLINICAL RESEARCH: FOCUS ON DIETARY CONTENT OF FERMENTABLE CARBOHYDRATE (FODMAPS) IN STANDARD RODENT CHOWS
Bibliographic record
Abstract
The Canadian Institute of Health Research (CIHR) and other scientific organizations have raised concern about the variability and lack of reproducibility of animal experimental results between laboratories. This concern includes studies investigating the microbiota, their metabolites and their impact on the host. Factors such as environment, stress, and sex have been identified as possible contributors, whereas composition of the regular diet, specifically quality of macronutrients, has received less attention. The prebiotic properties of dietary FODMAPs (fermentable oligo-, di-, mono-saccharides and polyols) are known to have a profound influence on the microbiota based on human studies, but the FODMAP content of standard animal diets has not been measured. The aim of this study was to analyze the FODMAP content of common rodent diets. Standard rodent chows used at rodent suppliers and research institutions were selected for analysis of FODMAP content, and three mill dates were collected for each chow. Using established protocols at Monash University, following sugar extraction, samples were analyzed in triplicate for excess fructose, lactose, sorbitol, mannitol, galacto-oligosaccharide (GOS: raffinose and stachyose), and total fructan content using high-performance liquid chromatography and enzymatic assays. The FODMAP content was then compared to both a custom-made low and high FODMAP rodent chow containing fructose, sorbitol, fructan and GOS at levels designed to mimic human consumption. Data was analyzed using unpaired t-tests. The custom-made low and high FODMAP diets contained 0.51 and 4.10g/100g total FODMAP, respectively. The total FODMAP content of the six standard chows was variable (Fig 1); the lowest was the Research Diets AIN93G Growing Rodent chow derived from cornstarch, the highest was the LabDiet 5001 Rodent chow derived from corn and soybean meal (0.40 vs 4.62 total FODMAP). When comparing the three lowest to the three highest chows, a significant difference in FODMAP content was observed (mean±SD: 0.89±0.57 vs 4.26±0.34; p=0.0009, unpaired t-test). The total oligosaccharide (GOS + fructan) component, the subgroup known to have the greatest influence on the microbiome, varied from 0.40–2.75. This study points to a significant variability in FODMAP content between commonly used standard rodent chows, which will likely impact gut microbiota composition, and gut physiology. Thus, the use of different standard rodent chows between laboratories might explain, at least partially, the lack of reproducible results in rodent experiments. Figure 1. Total FODMAP content of standard rodent chows compared to the custom-made low and high FODMAP chows CIHRCanadian Nutrition Society
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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 | 0.043 | 0.029 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.002 | 0.002 |
| 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".