Gut-brain axis: microbiota influence behavior and mental well-being

Tue, 12/03/2019 - 09:44


Expression of Neurogranin in the rat brain hippocampus, a calmodulin-binding protein, and a neuron specific protein commonly found in postsynaptic terminals (dendritic spines).

By Jennifer Sokolowski, MD, PhD.

Gut-microbiome interactions

On and in our bodies, microbes outnumber our cells by about ten-to-one. Studies have revealed that the microbiome influences neurogenesis, cognition, and stress responses, leading to increased interest in identifying factors that affect the gut microbiota, and a drive to understand pathways involved in the gut-brain axis.1

The composition of microbiota in the gut affects the immune system and influences neuroinflammation    . In addition, metabolic by-products from bacterial breakdown and fermentation have effects on the central nervous system, including modulation of blood-brain barrier permeability    and neuronal activity.2 Research has shown that gut-microbiome composition significantly impacts behavior, such as cognition, memory, anxiety and depression.3,4


CD11b/Integrin alpha M and Neurogranin expressed in the human cerebral cortex in microglia and neurons, respec-tively.Immunohistochemical analysis of CD11b/Integrin alpha M and Neurogranin in human brain cerebral cortex using Mouse Anti-Human/Equine CD11b/Integrin alpha M Monoclonal Antibody (MAB16991) and Sheep Anti-Human/Mouse/Rat Neurogranin Antigen Affinity-Purified Polyclonal Antibody (AF7947). Section was stained with NorthernLights 557-conjugated Anti-Mouse IgG Secondary Antibody (red; NL007) and Alexa Fluor® 488-conjugated Don-key Anti-Sheep IgG Secondary Antibody (green). Nuclei were counterstained with DAPI (blue). CD11b was localized to cytoplasm of microglia (red).


Antibiotics and the Gut-Brain Axis

A recent study by Jang et al.    ,5 showed that administration of antibiotics interferes with the gut flora and can predispose animals to colitis and anxiety-like behaviors. Pyrosequencing confirmed alterations in the gut flora after ampicillin treatment and showed that altered gut flora was sufficient to cause this effect, as transfer of fecal microbiota of ampicillin-treated (FAP) mice induced anxiety in recipient mice. FAP treatments led to increased serum levels of corticosterone, IL-6 and lipopolysaccharide. Moreover, the brain from these mice showed increased numbers of apoptotic cells (Caspase-3+), as well as recruitment of microglia (Iba1+), monocytes (CD11b+/CD45+) and dendritic cells (CD11b+/CD11c+) to the hippocampus. In addition, altered gut flora induced NF-κB, IL-1β, TNF-α expression in the brain, supporting the idea that altered fecal microbiota promoted neuroin-flammation. Interestingly, manipulation of the gut flora by administering probiotic Lactobacillus Reuteri alleviated anxiety and colitis and increased BDNF.


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This study reiterates that gut flora has an important influence on health, and adds additional insight into possible mechanisms through which microbiota can influence behavior and mental well-being. Ultimately, more and more research points to the importance of a symbiotic relationship between humans and "commensal" organisms in the gut, and is defining the ways that diet and antibiotics disrupt this balance.


Jennifer Sokolowski, MD, PhDJennifer Sokolowski, MD, PhD   
University of Virginia, Department of Neurosurgery
Jennifer is doing a postdoc while completing her residency in Neurosurgery and has background in basic science, specifically neuroscience, cell death, and immunology, as well as background in medicine and translational and clinical research.


References

  1. Ma, Q., Xing, C., Long, W., Wang, H. Y., Liu, Q., & Wang, R. F. (2019). Impact of microbiota on central nervous system and neurological diseases: The gut-brain axis. Journal of Neuroinflammation. https://doi.org/10.1186/s12974-019-1434-3
  2. Koh, A., De Vadder, F., Kovatcheva-Datchary, P., & Bäckhed, F. (2016). From dietary fiber to host physiology: Short-chain fatty acids as key bacterial metabolites. Cell. https://doi.org/10.1016/j.cell.2016.05.041
  3. Smith, P. A. (2015). The tantalizing links between gut microbes and the brain. Nature. https://doi.org/10.1038/526312a
  4. Frolinger, T., Sims, S., Smith, C., Wang, J., Cheng, H., Faith, J., … Pasinetti, G. M. (2019). The gut microbiota composition affects dietary polyphenols-mediated cognitive resilience in mice by modulating the bioavailability of phenolic acids. Scientific Reports. https://doi.org/10.1038/s41598-019-39994-6
  5. Jang, H. M., Lee, H. J., Jang, S. E., Han, M. J., & Kim, D. H. (2018). Evidence for interplay among antibacterial-induced gut microbiota disturbance, neuro-inflammation, and anxiety in mice. Mucosal Immunology. https://doi.org/10.1038/s41385-018-0042-3

 


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