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Intestinal microbiota influence the early postnatal development of the enteric nervous system

Authors

  • J. Collins,

    1. Department of Pediatrics, McMaster University, Hamilton, ON, Canada
    2. Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
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  • R. Borojevic,

    1. Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
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  • E. F. Verdu,

    1. Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
    2. Department of Medicine, McMaster University, Hamilton, ON, Canada
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  • J. D. Huizinga,

    1. Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
    2. Department of Medicine, McMaster University, Hamilton, ON, Canada
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  • E. M. Ratcliffe

    Corresponding author
    1. Department of Pediatrics, McMaster University, Hamilton, ON, Canada
    2. Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
    • Address for Correspondence

      Elyanne M. Ratcliffe, 1280 Main St. West, HSC 3A-27, Hamilton, ON, Canada L8S 4K1.

      Tel: 905-521-2100; fax: 905-521-2655; e-mail: ratcli@mcmaster.ca

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Abstract

Background

Normal gastrointestinal function depends on an intact and coordinated enteric nervous system (ENS). While the ENS is formed during fetal life, plasticity persists in the postnatal period during which the gastrointestinal tract is colonized by bacteria. We tested the hypothesis that colonization of the bowel by intestinal microbiota influences the postnatal development of the ENS.

Methods

The development of the ENS was studied in whole mount preparations of duodenum, jejunum, and ileum of specific pathogen-free (SPF), germ-free (GF), and altered Schaedler flora (ASF) NIH Swiss mice at postnatal day 3 (P3). The frequency and amplitude of circular muscle contractions were measured in intestinal segments using spatiotemporal mapping of video recorded spontaneous contractile activity with and without exposure to lidocaine and N-nitro-L-arginine (NOLA).

Key Results

Immunolabeling with antibodies to PGP9.5 revealed significant abnormalities in the myenteric plexi of GF jejunum and ileum, but not duodenum, characterized by a decrease in nerve density, a decrease in the number of neurons per ganglion, and an increase in the proportion of myenteric nitrergic neurons. Frequency of amplitude of muscle contractions were significantly decreased in the jejunum and ileum of GF mice and were unaffected by exposure to lidocaine, while NOLA enhanced contractile frequency in the GF jejunum and ileum.

Conclusions & Inferences

These findings suggest that early exposure to intestinal bacteria is essential for the postnatal development of the ENS in the mid to distal small intestine. Future studies are needed to investigate the mechanisms by which enteric microbiota interact with the developing ENS.

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