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Gut Microbiome-Brain Interactions in Mental Health: Implications for Mental Disorders

NAMHC Concept Clearance

Presenter

Nancy L. Desmond, Ph.D.
Chief, Neuroendocrinology and Neuroimmunology Program
Division of Neuroscience and Basic Behavioral Science (DNBBS)

Goal

The purpose of this initiative is to encourage hypothesis-driven research by multidisciplinary teams of investigators that will investigate mechanisms by which the gut microbiota modulate pre- and postnatal neurodevelopment, brain function, and behavioral domains relevant to the mission of NIMH. Such fundamental research may suggest avenues for future translational research.

Rationale

The number of microbial ecosystems that inhabit the gut far exceeds the number of eukaryotic cells. Variation in the composition of the microbiome across individuals is much greater than the variation in the microbiome composition within an individual. The Human Microbiome Project  (HMP) of the NIH Common Fund was established in 2007 to generate resources that would enable characterization of the human microbiota and analysis of their role in human health and disease. To date, researchers have characterized the microbial communities found at five different sites on the human body, including nasal passages, oral cavities, skin, gastrointestinal tract, and urogenital tract, and have begun analysis. Metagenomics tools have also been developed through the HMP which can be applied in future research.

The human microbiome may be an important link between our genes and our exposure to environmental factors. Because gene-environment interactions can affect complex behaviors, an enhanced understanding of contributing mechanisms like the gut microbiome may provide novel insights into neurodevelopment, brain structure and function, and behavior. Recent observations suggest that the gut microbiome plays a role in the development and function of brain circuits that subserve cognitive-emotional functions (e.g. Diaz Heijtz et al., 2010; Gareau et al. 2011; Clarke et al., 2012). Clinical studies also suggest potential links between infection and mental illness.

Working from the research foundation established by the HMP and related efforts in other countries, this initiative will encourage investigator teams to explore mechanisms by which the gut microbiome influences pre- and postnatal development as well as genes, signaling cascades, synaptic plasticity, and brain circuits related to affect, cognition and social behavior.

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References

Clarke G, Grenham S, Scully P, Fitzgerald P, Moloney RD, Shanahan F, Dinan TG, Cryan JF. The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner.  Mol Psychiatry. 2012 Jun 12. doi: 10.1038/mp.2012.77. [Epub ahead of print]

Diaz Heijtz R, Wang S, Anuar F, Qian Y, Björkholm B, Samuelsson A, Hibberd ML, Forssberg H, Pettersson S. Normal gut microbiota modulates brain development and behavior.  Proc Natl Acad Sci U S A. 2011 Feb 15;108(7):3047-52. Epub 2011 Jan 31.

Gareau MG, Wine E, Rodrigues DM, Cho JH, Whary MT, Philpott DJ, Macqueen G, Sherman PM. Bacterial infection causes stress-induced memory dysfunction in mice.  Gut. 2011 Mar;60(3):307-17. Epub 2010 Oct 21.