The Microbiota and the Gut-Brain Axis: Insights From the Temporal and Spatial Mucosal Alterations During Colonisation of the Germfree Mouse Intestine

Benef Microbes. 2012 Dec 1;3(4):251-9. doi: 10.3920/BM2012.0042.


The influence of the gut microbiota on the nervous system, brain development and behaviour, in particular during microbial colonisation of the host, has recently been receiving profound interest. Our time-resolved mining of combined data analyses of the ex-germfree mouse intestine during a 30-day course of colonisation with conventional mouse faecal microbiota (conventionalisation), shed light on temporal altered expression of genes of which the products influenced functions of the nervous system. Plasma tryptophan and kynurenine levels reflected high indoleamine dioxygenase activity, which was supported by significant temporal induction of the encoding gene in all gut tissues. However, the majority of genes associated with neuronal development and function were reduced. Colonic substance P elevation in response to conventionalisation was higher only after 30-days. These results support a functional microbiota-neurohumoral relationship during conventionalisation and suggest a delayed neuronal response that is elicited only after the microbiota accommodating homeostasis has been accomplished.

MeSH terms

  • Animals
  • Bacteria / growth & development
  • Bacteria / metabolism
  • Brain / metabolism*
  • Brain / physiology
  • Colon / metabolism
  • Colon / microbiology
  • Enzyme Activation
  • Feces / microbiology
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Germ-Free Life*
  • Homeostasis
  • Immunohistochemistry
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / genetics
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / microbiology
  • Intestine, Small / metabolism
  • Intestine, Small / microbiology*
  • Kynuramine / blood
  • Male
  • Metagenome*
  • Mice
  • Mice, Inbred C57BL
  • Neurons / cytology
  • Neurons / metabolism
  • Neurons / physiology
  • Stress, Physiological
  • Substance P / metabolism
  • Synaptic Transmission
  • Time Factors
  • Tryptophan / blood


  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Substance P
  • Kynuramine
  • Tryptophan