A283 SECRETIONS OF INTESTINAL MICROBIOTA INCREASE THE EXCITABILITY OF VAGAL AFFERENT NEURONS VIA A PROTEASE ACTIVATED RECEPTOR 2 (PAR2)-DEPENDENT PATHWAY.
Bibliographic record
Abstract
The intestinal microbiota has recently been shown to have pronounced effects on the central nervous system (CNS). However, it is presently unknown how intestinal microbes signal to the CNS. There are two afferent neural pathways linking the intestine and the CNS: the spinal afferent pathway and the vagal afferent pathway. We have previously found that intestinal microbes decrease the excitability of spinal afferent neurons via the actions of serine proteases on protease activated receptors. The present work was conducted to determine if intestinal microbiota can change the excitablitiy of the vagal afferent pathway as the spinal afferent pathway. Perforated patch clamp electrophysiology was used to measure the excitability of the cultured vagal afferent neurons, whose cell bodies lie in the nodose ganglia. Dissociated nodose ganglion neurons were cultured overnight either in normal media or media containing supernatant from a human intestinal microbial community named microbial ecosystem therapeutics (MET-1). Nodose ganglion neuronal excitability was assayed by measuring the threshold amount of current required to elicit an action potential, the rheobase. MET-1 supernatant concentration-dependently increased the excitability of nodose ganglion neurons by decreasing the rheobase. The increase in excitability elicited by MET-1 supernatant was blocked by using a cocktail of protease inhibitors. Furthermore on using specific protease inhibitors, it was found that only cysteine protease inhibitor (E-64, 1:30000) was able to inhibit the effect of MET-1. Similarly PAR2 antagonist (GB-83, 10 µM) also blocked the effect of MET-1 on rheobase of nodose neurons. In contrast to spinal afferent neurons, which are inhibited by MET-1 supernatant, vagal afferent neurons are excited. MET-1 induced increased in excitability is cysteine protease dependent and is mediated by the PAR2 receptor. The increased excitability of vagal afferent neurons in response to microbial secretions suggest that the vagal pathway may be an important neural conduit allowing microbial modulation of CNS function. CCC
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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 | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 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".