A53 FECAL BIOACTIVE PHOSPHOLIPIDS AS TRIGGERS OF INTESTINAL HYPERSENSITIVITY IN IRRITABLE BOWEL SYNDROME
Bibliographic record
Abstract
Abstract Background Chronic abdominal pain is the most common complaint of patients with gastrointestinal disorders. Its treatment is of limited efficacy as the pathophysiology is poorly understood. The gut microbiome has been shown to affect host physiology, including the neural system function, and growing evidence suggests that it plays an important role in pain perception. Gut microbiota produces a large variety of molecules that can regulate pain perception, such as histamine or bioactive lipids. Phospholipid mediators (PLM) are signaling molecules linked to neurogenic pain as by-products of inflammatory processes in mammals. But it is unknown whether bacteria can produce PLM and whether they play any role in visceral hyperalgesia. Purpose To investigate whether PLM are present in stool of patients with chronic abdominal pain, and whether they have potential to induce visceral hypersensitivity. Method Stool samples from 27 patients with irritable bowel syndrome (IBS) were collected both during periods of severe and minimal/no pain. The fecal concentration of two PLM (lipid A and lipid B) was determined by ELISA. The passage of lipid A and lipid B through the intestinal barrier was determined ex vivo using Ussing chambers and in vivo by their intracolonic instillation, and their levels assessed in the serosal compartment and the serum, respectively, by ELISA. We used primary cultures of sensory neurons from the dorsal root ganglia (DRG) of conventional mice (SPF) to study the neuronal activation in vitro. Calcium mobilization in DRG sensory neurons was measured by an inverted fluorescence microscope using a fluorescent probe Fluo-4 (1mM) after stimulation with different concentration of lipid A or lipid B. Visceral sensitivity in vivo after intracolonic instillation of combined lipids A and B was evaluated by colorectal distension. Result(s) The concentration of lipid A (p=0.001) and lipid B (p=0.002) in stool was significantly higher in IBS patients when experiencing severe abdominal pain compared to periods of minimal pain. The concentration of lipid A (p=0.03; p=0.07) and lipid B (p=0.018; p=0.018) in the serosal compartment and in the serum, respectively, was higher compared to the control condition. The percentage of neurons responding to lipid A or lipid B was significantly higher compared to the control condition, at all tested concentrations. Finally, combined lipid A and lipid B induced visceral hypersensitivity within 10 minutes (p=0.0433) and 90 minutes (p=0.0020) after intracolonic instillation. Conclusion(s) Our data suggest that PLM can be found in stool of patients with abdominal pain, that they cross the colonic barrier and increase visceral sensitivity. Further studies are needed to ascertain whether gut bacteria produce these PLM and investigate the precise mechanisms by which PLM induce hyperalgesia. Please acknowledge all funding agencies by checking the applicable boxes below CIHR, Other Please indicate your source of funding; Weston Family Foundation 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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| 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 | 0.000 | 0.000 |
| 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".