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.