V3
Mindy Ovadiuc
June 1, 2017
Sharon, Gil, Timothy R. Sampson, Daniel H. Geschwind, and Sarkis K.
Mazmanian. ”The Central Nervous System and the Gut Microbiome.” Cell
167.4 (2016): 915-32. Web.
Prenatal neurodevelopment, postnatal neurological maintenance and old
age neurodegeneration are dependent upon intrinsic molecular signals
from the gut, some microbial in origination, as well as extrinsic
environmental cues (Zoetendal et al. 2008; Chang et al. 2009). The
development, maturation and maintenance of the immune system is
intimately tied to the composition and presence or lack of host
associated microorganisms. Communication between the gut microbiome and
the brain via bacterial secondary metabolites, metabolic precursors,
hypothalamic–pituitary–adrenal axis (HPA) activation as well as immune
and vagus nerve signaling has been implicated in neuropsychiatric
conditions, such as autism spectrum disorders (ASDs), anxiety,
depression, schizophrenia, Parkinson’s disease (PD), Alzheimer’s disease
(AD) and cognition deficits. Some species of microbes possibly
potentiate states of immunological diseases, such as inflammatory bowel
disease (IBD), type I diabetes and asthma(Round & Mazmanian 2009;
Clarke et al. 2013; Foster & McVey Neufeld 2013; Krajmalnik-Brown et
al. 2015). Germ-free (GF) mice, totally void of microorganisms, exhibit
abnormal behaviors compared to conventional specific pathogen free (SPF)
mice, including hyperactivity, increased risk taking behaviors as well
as learning and memory deficits. GF mice also have compromised blood
brain barriers (BBBs) and augmented prefrontal cortex myelination.
Colonization or antibiotic induced depletion of microbiota (GM) in mice
confers changes in the following processes: BBB integrity, myelination,
microglial maturation, microglial effects, animal behavior,
neurogenesis, neutrophin expression, neurotransmitters and their
receptors as well as neuronal survival growth and
differentiation(Ogbonnaya et al. 2015; Luczynski et al. 2016).
Neurodevelopment, therefore health, is influenced by host associated
microorganisms. The establishment of neuronal circuits moreover neuronal
fate, function and survival is mediated by microorganisms via
neurotrophic factor signaling and reception. Differences in GF mice
versus SPF mice anatomy prove that exposure to microbes very early in
life keeps neurogenesis in check throughout the lifetime of the host. GF
mice have immature microglia that have viral and microbial associated
molecular pattern recognition (MAMP) deficits. The administration of short chain fatty acids (SCFAs), a microbial metabolic byproduct, can
rescue these deficits(Hoban et al. 2016; Erny et al. 2015). GF mice have
permeable BBBs and exhibit decreased expression of brain epithelial
tight junction proteins. The administration of SCFAs can amend BBB
permeability.