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Role of bacteria overlooked in mental disorders.

The past few years have seen numerous studies detailing the effect that the brain can have on gut bacteria (top-down control). It is known, for instance, that stress might modulate intestinal microbiota. However, recent research - much of it preclinical - suggests that the contrary also is true: Gut bacteria can influence the brain. These new findings are very important, for they justify consideration of patients' gastrointestinal health while treating psychiatric disorders.

A recent article published by Dr. Serguei O. Fetissov and Dr. Pierre Dechelotte in France, for example, suggests that eating disorders, major depressive disorder, and narcolepsy might originate outside the brain and might be a dysfunction of the "gutbrain axis involving the humoral immune system" (Curr. Opin. Clin. Nutr. Metab. Care 2011;14:477-82). Some of the strongest evidence of this connection can be found in eating disorders.

Dr. Fetissov and Dr. Dechelotte propose that the composition of the gut microbiome might represent a "key causative factor triggering production of certain neuropeptide-reactive autoAbs, which in turn will modulate corresponding peptidergic signaling resulting in modification of eating-related behaviors and eventual. Another study, by Dr. K.M. Neufeld and colleagues at McMaster University, Hamilton, Ont., indicates that intestinal microbiota play a role in the development of the central nervous system and behavior. They evaluated the basic behavioral characteristics of germ-free versus specific pathogen-free adult mice. The former have been found to show a hyper responsive hypothalamic-pituitary-adrenal axis following stress, compared with regular laboratory mice (specific pathogen-free mice). However, actual behavior had not been previously evaluated. Interestingly enough, Dr. Neufeld's study found that germ-free mice showed decreased anxiety. They engaged in risky behavior more often and for longer periods of time than did regular mice (specific pathogen-free mice). Germ-free mice also exhibited an up-regulation of the brain-derived neurotrophic factor in the dentate gyrus of the hippocampus, as well as down-regulation of 5HT1A receptors and NMDA receptor expression, all of which have been associated to the stress response and to emotional behavior (Neurogastroenterol. Motil. 2011;23:255-64).

A related study showed that the behavioral phenotype of germ-free mice can be altered by administering them gut bacteria from regular laboratory mice, or specific pathogen-free mice. The result was that the behavior of the treated germ-free mice was similar to that of specific pathogen-free mice (that is, they showed an increase in anxiety). Moreover, polymerase chain reaction analysis of hippocampal tissue revealed a decrease in the expression of brain-derived neurotrophic factor (Gastroenterology 2011;140:S-57).

Not only do gut microbiota seem to play a role in behavior and response to stress, but stress seems to, in turn, affect the gut microbiota - a two-way street of some sort. A study published this year by Dr. Michael T. Bailey and his colleagues indicates that social stress can have a profound impact on the population of various intestinal microbiota. The researchers used social disruption stress, a form of social stress used with mice and known to function as a chronic social stressor. They found that exposure to this stressor decreased the number of bacteria of the genus Bacteroides, but increased the number of bacteria in the genus Clostridium. As expected, social disruption stress also increased levels of interleukin-6, a pro-inflammatory cytokine whose expression is known to increase as a result of stress, and Monocyte chemotactic protein-1, which recruits monocytes to sites of injury and whose expression is also regulated by stress. Interestingly enough, however, when mice were treated with antibiotics (to decrease microbiota) prior to social disruption stress, the mice did not show increased interleukin-6 or MCP-1 level. These results suggest that increases in cytokines because of stressors are dependent on microbiota (Brain Behav. Immun. 2011;25:397-407).

Given these new findings, further research should be devoted to under standing the role of microbiota in behavior and mental illness.

Ms. Bouchard is pursuing a PhD in neuroscience at Texas A&M University, College Station. She has no conflicts of interest.
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Title Annotation:COMMENTARY
Author:Bouchard, Sioui Maldonado
Publication:Clinical Psychiatry News
Date:Sep 1, 2011
Words:651
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