Normal gut microbiota modulates brain development and behavior. Proc Natl Acad Sci USA

Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 02/2011; 108(7):3047-52. DOI: 10.1073/pnas.1010529108
Source: PubMed


Microbial colonization of mammals is an evolution-driven process that modulate host physiology, many of which are associated with immunity and nutrient intake. Here, we report that colonization by gut microbiota impacts mammalian brain development and subsequent adult behavior. Using measures of motor activity and anxiety-like behavior, we demonstrate that germ free (GF) mice display increased motor activity and reduced anxiety, compared with specific pathogen free (SPF) mice with a normal gut microbiota. This behavioral phenotype is associated with altered expression of genes known to be involved in second messenger pathways and synaptic long-term potentiation in brain regions implicated in motor control and anxiety-like behavior. GF mice exposed to gut microbiota early in life display similar characteristics as SPF mice, including reduced expression of PSD-95 and synaptophysin in the striatum. Hence, our results suggest that the microbial colonization process initiates signaling mechanisms that affect neuronal circuits involved in motor control and anxiety behavior.

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    • "Gut microbiota is an important modulator of brain development and function (Diaz Heijtz et al., 2011), and pathogens or dysbiosis can either lead to or protect from inflammatory diseases of the central nervous system, such as multiple sclerosis (Ochoa-Reparaz et al., 2011). "
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    ABSTRACT: Gnotobiology technology for the breeding of experimental mice originated in the first half of the twentieth century. Earlier studies conducted in germ-free animals revealed the importance of the microbiota in the development of the immune system, gut morphology, and metabolism. These seminal studies have been confirmed and complemented by recent work that exploits the use of modern gnotobiotic technology as well as the combination of high-throughput molecular techniques to study the composition and metabolic capacity of the intestinal microbiota. From a historical perspective, this chapter discusses the evolution of theory concerning complex host-microbiota interactions and probiotics species. It also reviews the current evidence for a role of maladaptive interactions in the development of disease within and beyond the gastrointestinal tract.
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    • "Therefore, the enhanced locomotor activity could be attributed to the enhancement in striatal DA neurotransmission. Past studies have demonstrated that GF mice exhibited increased DA concentration and elevated DA turnover rate in the striatum compared to SPF mice [9]. Thus, the effects of chronic live PS128 ingestion on locomotor activity we observed might be the additional change over an already enhanced DA concentration and turnover. "
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    ABSTRACT: Probiotics, defined as live bacteria or bacterial products, confer a significant health benefit to the host, including amelioration of anxiety-like behavior and psychiatric illnesses. Here we administered Lactobacillus plantarum PS128 (PS128) to a germ-free (GF) mouse model to investigate the impact of the gut-brain axis on emotional behaviors. First, we demonstrated that chronic administration of live PS128 showed no adverse effects on physical health. Then, we found that administration of live PS128 significantly increased the total distance traveled in the open field test and decreased the time spent in the closed arm in the elevated plus maze test, whereas the administration of PS128 had no significant effects in the depression-like behaviors of GF mice. Also, chronic live PS128 ingestion significantly increased the levels of both serotonin and dopamine in the striatum, but not in the prefrontal cortex or hippocampus. These results suggest that the chronic administration of PS128 is safe and could induce changes in emotional behaviors. The behavioral changes are correlated with the increase in the monoamine neurotransmitters in the striatum. These findings suggest that daily intake of the Lactobacillus plantarum strain PS128 could improve anxiety-like behaviors and may be helpful in ameliorating neuropsychiatric disorders.
    Full-text · Article · Nov 2015 · Behavioural brain research
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    • "First of all, GF mice show reduced anxietylike behavior, compared to conventionally-housed mice, in the elevated plus maze (EPM) and light/dark test (Heijtz et al., 2011; Neufeld et al., 2011b; Clarke et al., 2013). Second of all, reconstitution of GF mice with strain-matched microbiota early in life is able to normalize many of the behaviors (Heijtz et al., 2011; Clarke et al., 2013), whereas reconstitution of GF mice in adulthood was not able to change the reduced trait anxiety–like phenotype observed in the EPM (Neufeld et al., 2011a). Interestingly, one can argue that the behavioral phenotype is linked directly to the microbiota, as the transfer of SPF Balb/C microbiota to GF Swiss Webster (SW) mice reduced exploratory behavior compared to normal SW mice, while transfer of SPF SW microbiota to GF Balb/C mice increased exploratory behavior compared to normal Balb/C mice (Bercik et al., 2011a). "

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