Close

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

Collins J, Borojevic R, Verdu EF, Huizinga JD, Ratcliffe EM.

Neurogastroenterol Motil. 2014 Jan;26(1):98-107. doi: 10.1111/nmo.12236. Epub 2013 Oct 8.

PMID: 24329946

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.

The gut requires a nervous system to function:  life depends, therefore, on having an operational nervous system in the gastrointestinal tract once feeding begins after birth.  This nervous system needs to adapt to changes in the outside world, such as interactions with bacteria.  We have found that in the absence of bacteria the nerves in the gut form differently than when bacteria are present.  This suggests that bacteria are necessary for the normal adaption of the gastrointestinal nervous system in early life.

This study tested the hypothesis that the colonization of the intestine by microbiota influences the postnatal development of the enteric nervous system.
• The enteric nervous system was studied in whole mount preparations of small intestine from germ-free and specific pathogen-free mice. Intestinal motility was measured using spatiotemporal mapping of video recorded
spontaneous contractile motility.
• The myenteric plexus of the jejunum and ileum of germ-free mice was structurally abnormal compared to
specific pathogen-free mice, with a decrease in nerve density, a decrease in number of neuronal cell bodies per
ganglion but a proportionate increase in nitrergic neurons.
• The frequency and amplitude of muscle contractions was decreased in germ-free compared to specific pathogen-free jejunum and ileum.
• The structural and functional abnormalities of the enteric nervous system in germ-free mice suggest that microbiota play a role in the adaptation of the enteric nervous system to the extrauterine environment.

Share on FacebookTweet about this on TwitterShare on Google+Share on LinkedIn