A300 DIET-MICROBIOTA INTERACTIONS UNDERLIE SYMPTOMS IN IBS
Bibliographic record
Abstract
The mechanisms underlying IBS are poorly understood but growing evidence suggests that immune activation and the microbiota may be involved. We recently demonstrated that a diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) improves symptoms in IBS patients and this is correlated with decreased mast cell activation and changes in the microbiota composition. Thus, FODMAPs may be a useful tool to evaluate IBS mechanisms. To investigate the interplay of host’s gut function, intestinal microbiota and immune factors in response to FODMAPs in the humanized IBS mouse model. Germ-free NIH Swiss mice were colonized with fecal microbiota from two IBS patients (non-constipation) with a high (P1) or low (P2) urinary histamine level (n=20 mice /patient), suggesting differing levels of immune activation. Mice were assigned to a custom-made low or high FODMAP diet (LF and HF, respectively). Three weeks later, GI transit (beads study), cecal volume (CT scan) and intestinal permeability (FITC-Dextran) were assessed. Animals were then euthanized and neuronal excitability assessed by patch clamp recordings of DRG neurons (action potential rheobase) exposed to colonic supernatants and changes in mechanosensitivity of single unit afferent recordings in mouse distal colon from mice receiving LF or HF diets. P1 mice receiving a HF diet had slower GI transit (p=0.02), increased cecal volume (p=0.004), indicative of increased gas content, increased permeability (FITC-Dextran: p=0.04), and lower weight gain (p=0.04) compared to P1 mice on a LF diet. In electrophysiological studies, the rheobase was decreased (24%; p=0.003) and mechanosensitivy increased (p=0.06) in the HF compared to the LF mice. The decreased rheobase was blocked by a H1 or a PAR2 antagonist. In contrast, P2 mice receiving the HF diet displayed modest increase in cecal volume (p=0.02) but no differences in GI transit, permeability or weight compared to those on the LF diet. The rheobase was modestly decreased (17%, p<0.05) but no changes were found in mechanosensitivity. Fermentable carbohydrates cause changes in GI function that likely underlie symptoms of IBS, and the magnitude of these functional changes is determined by gut microbiota. Our data suggests the microbiota-diet interactions play a key role in IBS pathogenesis and symptom generation. First two authors contributed equally to this work. Funded by grants from CIHR and CAG. CAG, CIHR
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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 | 0.000 |
| 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 | 0.001 | 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".