The Relationship Between Intestinal Microbiota and the Central Nervous System in Normal Gastrointestinal Function and Disease
Section snippets
The Intestinal Microbiota
The gut contains a vast and complex microbial ecosystem, comprising mainly bacteria, of which most are strict anaerobes; it also includes fungi and viruses,5, 6, 7 but only bacteria are considered in this review. Commensal bacteria instruct the immune and physiologic systems throughout life and are responsible for the presence of inflammatory and immune cells in the healthy gut: so-called “physiologic” or “controlled” inflammation. The term physiologic inflammation refers to the presence of
Influence of the Microbiota on the GI Tract
A strategy that is commonly used to investigate interactions between the microbiota and the host is to compare germ-free animals with those colonized with a single strain or multiple strains of bacteria.17 The microbiota influences expression of a broad array of host genes. A comparison of germ-free mice and mice colonized with Bacteroides thetaiotaomicron, a prominent member of the adult mouse and human gut microflora, showed that the microbiota modulate the expression of genes that regulate
Influence of GI Physiology on the Microbiota
Although the microbiota exert a broad influence on host physiology, the converse is also true. Under normal conditions, the GI tract provides a stable habitat for commensal bacteria that supports its structural and functional integrity (Figure 2A). Disturbance of normal GI physiology destabilizes the habitat, resulting in changes in its microbial composition. An example of this is the change in the bacterial composition of the GI tract after interruption of normal interdigestive motility in the
Ability of the Brain to Influence Microbiota
Several animal studies suggest that psychological stress alters GI flora, but each of these studies has limitations. Tannock and Savage36 reported changes in GI flora of mice stressed by deprivation of food, water, or bedding. However, these environmental changes would be expected to have a direct effect on the microbiota that is independent from a stress response. Bailey and Coe37 used maternal separation to demonstrate a reduction in lactobacilli for ≤7 days in infant rhesus monkeys; these
Ability of Microbiota to Influence the Brain and Behavior
The most compelling evidence of a GI microbe–brain interaction is the often dramatic improvement in patients with hepatic encephalopathy after the administration of oral antibiotics and laxatives.4 Although the mechanistic basis for hepatic encephalopathy is incompletely understood,45 there is some evidence from a rat model of hepatic failure that certain bacteria can produce a ligand for the benzodiazepine receptor that may contribute to the encephalopathy.46 Observations in human beings offer
Probiotics
Probiotics are microbes (bacteria or yeast) that confer health benefits to the host when administered in sufficient quantity. They have been shown to influence function in a variety of organs, including the nervous system. Several studies report the effects of probiotics on the GBA and in models of altered behavior.
In rats subjected to water-avoidance stress, intestinal barrier function was reduced, and bacterial adherence to the epithelium was increased. In addition, commensal bacteria
Microbiota–GBA and Disease
Evidence is increasing for a role of the GBA in the pathogenesis of IBD. Imbalance between the sympathetic and parasympathetic outflow from the central nervous system has been reported in patients with IBD81, 82, 83 and may be associated with behavioral change. For example, depression has been correlated with Crohn's disease, stress, and ulcerative colitis in separate groups of patients.84 A controlled study found an increased prevalence of depression in patients with IBD.85 It is difficult to
Acknowledgments
The authors thank Dr Elena F. Verdu, Emmanuel Denou, PhD, and Jean-Eric Ghia, PhD, for their contributions to the work shown in this manuscript.
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Conflicts of interest The authors disclose the following: Dr S.M. Collins received a grant in aid from the Nestle Research Institute, Switzerland, and from Institut Rossel, Montreal, Canada. Dr P. Bercik received a grant in aid from the Nestle Research Institute, Switzerland.
Funding The work was supported primarily by the Canadian Institutes of Health Research (CIHR) and by unrestricted grants from the Nestle Research Institute, Switzerland, and Institut Rosell, Montreal, Canada.