A309 ANTIBIOTIC DRIVEN CHANGES IN GUT MOTILITY HIGHLIGHT DIRECT MODULATION OF ENTERIC NERVOUS SYSTEM
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Abstract
Background
The microbiome-gut-brain axis is a bidirectional network that influences brain chemistry and behaviour. Antibiotics are known to alter several aspects of gut-brain signaling but the underlying mechanisms remain equivocal. As prior assessments of these mechanisms have been limited to changes in gut microbiota, we hypothesized that antibiotics may directly modulate neurons and neural reflexes.
Aims
To identify whether transient exposure of the gastrointestinal tract to antibiotics can acutely modulate peristaltic reflexes that depend on the enteric nervous system (ENS).
Methods
4 cm colon segments excised from adult male Swiss Webster mice were submerged in an organ bath chamber (34°C oxygenated Krebs buffer solution) and cannulated at both the oral and anal ends. Gut lumens were perfused with Krebs saline control followed by either Krebs diluted Bacitracin (1, 3 or 10 mM) or Penicillin V (3, 10, 30 or 100 mM). Gut motility was recorded by video which was subsequently converted to spatiotemporal diameter maps for quantitative analysis. Paired t-tests were performed for before and after measurements.
Results
Alterations in ENS-dependent propagating contractile cluster (PCC) velocity and frequency were evoked by Bacitracin at concentrations of 1, 3 and 10 mM and Penicillin V above 10 mM. For Bacitracin, PCC velocity (mm/s) increased from 0.23 ± 0.06 to 0.35 ± 0.13 (n=20, P<0.001) at 1 mM, from 0.28 ± 0.11 to 0.33 ± 0.13 (n=20, P= 0.034) at 3 mM and increased from 0.26 ± 0.11 to 0.28 ± 0.11 (n=20, P=0.8) at 10 mM. Similarly, PCC frequency (Hz) increased from 0.009 ± 0.002 to 0.011 ± 0.003 (n=20, P=0.037) at 1 mM, from 0.012 ± 0.003 to 0.013 ± 0.003 (n=20, P=0.05) at 3 mM and remained at 0.01 ± 0.004 Hz (n=20, P=0.9) at 10 mM. Similar results were produced in experiments using >10 mM Penicillin V. PCC velocity (mm/s) increased from 0.21 ± 0.05 to 0.22 ± 0.04 (n=20, P=0.15) at 10 mM, 0.17 ± 0.04 to 0.54 ± 0.2 (n=16, P<0.001) at 30 mM and from 0.17 ± 0.04 to 0.65 ± 0.2 (n=16, P<0.001) at 100 mM. PCC frequency (Hz) increased from 0.01 ± 0.001 to 0.012 ± 0.002 (n=20, P=0.013) at 10 mM, from 0.01 ± 0.002 to 0.04 ± 0.03 (n=16, P=0.008) at 30 mM and from 0.01 ± 0.002 to 0.05 ± 0.03 (n=16, P=0.001) at 100 mM.
Conclusions
These experiments suggest that luminal antibiotics acutely alter ENS dependent reflexes. Therefore, studies attributing the effects of antibiotics solely to disruption of the gut microbiota should be interpreted with caution.
Funding Agencies
CIHRInternational Development Research Council (IDRC) Canada-Israel Joint Research Program #26749
