A53 SACCHAROMYCES BOULARDII CNCM I-745 IMPROVES ANXIETY-LIKE BEHAVIOR AND RESCUES DYSMOTILITY IN A HUMANIZED MOUSE MODEL OF IRRITABLE BOWEL SYNDROME WITH CO-MORBID ANXIETY
Bibliographic record
Abstract
Abstract Background Irritable bowel syndrome (IBS) is one of the most common conditions seen by gastroenterologists for which there is no effective cure. The pathophysiology of IBS is multifactorial and poorly understood, but the condition is characterized by chronic abdominal pain accompanied by altered bowel habits in the absence of an underlying structural abnormality. IBS is frequently associated with psychiatric co-morbidities such as anxiety and depression and has been considered a disorder of gut-brain communication. We previously developed a humanized mouse model of IBS with co-morbid anxiety (IBS+A) by colonizing germ-free mice with fecal microbiota of IBS+A patients. Aims To test the therapeutic potential of the probiotic yeast Saccharomyces boulardii CNCM I-745 (S. bou) in preventing the transfer of the IBS+A phenotype and investigated underlying mechanisms. Methods Germ-free Swiss-Webster mice were colonized with fecal microbiota from an IBS+A patient or from a healthy subject (controls) and after three weeks they were gavaged daily for two weeks with 3g/kg/day of the probiotic S. bou (Biocodex–France) or water. Behavior, intestinal motility and permeability were assessed at sacrifice. Potential mechanisms were assessed by microbiota 16S rRNA gene sequencing, gene expression by Nanostring Counter Gene Expression and indole quantification by absorption using Kovak’s reagent. Results IBS+A colonized mice developed 25% faster gastrointestinal transit (P<0.05) and had a 3-fold longer latency time in the step-down test (P<0.001), indicative of anxiety-like behaviour compared with controls. S. bou normalized gastrointestinal transit (P<0.05) and shortened by 50% the step-down latency (P<0.01), compared to water-treated mice. Microbiota of IBS+A colonized mice had higher abundance of Unc. Erysipelotrichaceae and Unc. Coriobacteriaceae, and lower abundance of Oscillospira, Weissela, and Fructubacillus. S. bou treatment prevented these changes and the microbiota was similar to controls. Predicted function analysis in S. bou treated mice suggested higher number of genes implicated in indole biosynthesis (P<0.05) and S. bou increased indole levels by 20% in vitro. Finally, Trpv1, a gene implicated in visceral hypersensitivity and anxiety, was increased by 2-fold in IBS+A colonized mice compared with controls (P<0.001), and this was reverted by 20% (P<0.05) by S. bou treatment. Conclusions Our data indicate that Saccharomyces boulardii CNCM I-745 supplementation improves the intestinal and behavioral phonotype that is induced by IBS+A microbiota in mice. Putative mechanisms include regulation of indole production by bacteria and regulation of host Trpv1 gene expression. The results prompt investigation of S. bou in IBS patients with co-morbid anxiety. Funding Agencies Biocodex – Gentilly – France
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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 | 0.000 |
| 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".