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The gut microbiome restores intrinsic and extrinsic nerve function in germ-free mice accompanied by changes in calbindin.

AbstractBACKGROUND:
The microbiome is essential for normal myenteric intrinsic primary afferent neuron (IPAN) excitability. These neurons control gut motility and modulate gut-brain signaling by exciting extrinsic afferent fibers innervating the enteric nervous system via an IPAN to extrinsic fiber sensory synapse. We investigated effects of germ-free (GF) status and conventionalization on extrinsic sensory fiber discharge in the mesenteric nerve bundle and IPAN electrophysiology, and compared these findings with those from specific pathogen-free (SPF) mice. As we have previously shown that the IPAN calcium-dependent slow afterhyperpolarization (sAHP) is enhanced in GF mice, we also examined the expression of the calcium-binding protein calbindin in these neurons in these different animal groups.
METHODS:
IPAN sAHP and mesenteric nerve multiunit discharge were recorded using ex vivo jejunal gut segments from SPF, GF, or conventionalized (CONV) mice. IPANs were excited by adding 5 μM TRAM-34 to the serosal superfusate. We probed for calbindin expression using immunohistochemical techniques.
KEY RESULTS:
SPF mice had a 21% increase in mesenteric nerve multiunit firing rate and CONV mice a 41% increase when IPANs were excited by TRAM-34. For GF mice, this increase was barely detectable (2%). TRAM-34 changed sAHP area under the curve by -77 for SPF, +3 for GF, or -54% for CONV animals. Calbindin-immunopositive neurons per myenteric ganglion were 36% in SPF, 24% in GF, and 52% in CONV animals.
CONCLUSIONS & INFERENCES:
The intact microbiome is essential for normal intrinsic and extrinsic nerve function and gut-brain signaling.
AuthorsK A McVey Neufeld, A Perez-Burgos, Y K Mao, J Bienenstock, W A Kunze
JournalNeurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society (Neurogastroenterol Motil) Vol. 27 Issue 5 Pg. 627-36 (May 2015) ISSN: 1365-2982 [Electronic] England
PMID25727007 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2015 John Wiley & Sons Ltd.
Chemical References
  • Calbindins
  • Pyrazoles
  • TRAM 34
Topics
  • Action Potentials (drug effects, physiology)
  • Animals
  • Calbindins (metabolism)
  • Enteric Nervous System (drug effects, metabolism, physiology)
  • Female
  • Gastrointestinal Microbiome (physiology)
  • Germ-Free Life
  • Jejunum (innervation, metabolism, microbiology)
  • Mice
  • Myenteric Plexus (drug effects, metabolism, physiology)
  • Neurons, Afferent (drug effects, physiology)
  • Pyrazoles (pharmacology)
  • Specific Pathogen-Free Organisms

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