The gut microbiome restores intrinsic and extrinsic nerve function in germ‐free mice accompanied by changes in calbindin
Abstract
Background: 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. IPAN s 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 IPAN s 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.
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In germ-free mice, colonization of the gut microbiota is critical for the development and maturation of the ENS.
“In germ-free mice, colonization of the gut microbiota is critical for the development and maturation of the ENS51.”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [51]
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- Authors
- McVey Neufeld, K. A., Perez‐Burgos, A., Mao, Y. K., Bienenstock, J., & Kunze, W. A.
- Affiliations
- McMaster Brain‐Body Institute at St Joseph's Healthcare Hamilton ON Canada
- St. Joseph’s Healthcare Hamilton (CA)
- Venue
- Neurogastroenterology & Motility
- Publisher
- Wiley
- Published
- 2015-03-02
- Volume
- 27
- Issue
- 5
- Pages
- 627-636
- ISSN
- 1350-1925 (ISSN-L)
- 1365-2982
- OpenAlex
- W2092859492
- Cited by
- 142
- References
- 50
- Citations by year
- 2026: 8 · 2025: 15 · 2024: 13 · 2023: 5 · 2022: 18 · 2021: 13 · 2020: 22 · 2019: 6 · 2018: 14 · 2017: 8 · 2016: 18 · 2015: 2
- FWCI
- 14.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurogastroenterology & Motility (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Natural Sciences and Engineering Research Council of Canada (371955-2009)
- Father Sean O'Sullivan Research Council, St Joseph's Healthcare
- Guglietti Family Foundation
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Surgery › Congenital gastrointestinal and neural anomalies
- Keywords
- gut microbiota, germ-free mice, calbindin, slow afterhyperpolarization, gut-brain signaling, enteric nervous system, conventionalization, TRAM-34, calcium-binding proteins
- MeSH terms
- Gastrointestinal Microbiome, Action Potentials, Animals, Female, Germ-Free Life, Jejunum, Myenteric Plexus, Neurons, Afferent, Pyrazoles, Specific Pathogen-Free Organisms, Enteric Nervous System, Mice, Calbindins
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