A recent study published in Nature describes a novel molecular mechanism describing how the gut microbiome influences brain health.
Mammalian organisms are endowed with a flourishing community of microorganisms within their gut. The human gut has an average of 30 trillion bacteria living within it. The scientific community refers to this as the microbiome. These microorganisms are required for efficient nutrient absorption and as a mechanism to combat pathogens that can invade our bodies.
Increasingly understood role of the gut microbiome on health
Until recently, the role of these microorganisms was only appreciated in the context of gastrointestinal health. However, several exciting studies in the last few decades have indicated the presence of a distinct gut-brain-axis, a relationship that describes the role of the microbiome on brain health. Other studies have shown that a disturbance in the gut microbial community is associated with mental disorders such as anxiety and depression. Behavioral deficits that prevent people from overcoming fear and develop irrational anxiety have been suggested to be linked to disturbances in gut health. The gut microbiome is disturbed in auto-immune disorders such as inflammatory bowel disease (IBD), psoriasis, and multiple sclerosis. Interestingly there is a close association of auto-immune disorders with anxiety, depression, and mood disorders. However, the molecular details of how gut microbiome influences these aspects of behavior are unknown.
Gut microbiome affects fear and anxiety in mice
Collaborative studies by researchers at Weill Cornell Medicine, Boyce Thompson Institute, Broad Institute at MIT and Harvard, and Northwell Health have revealed molecular mechanism of how gut microbiome plays a role in shaping response to fear and anxiety in mice. The investigators to started their studies by first demonstrating a relationship between gut microbial community and brain health using fear-conditioning maneuvers in mice with defective microbial communities. These models allow researchers artificially deplete the normal gut flora within mice (also called germ free mice) and then study molecular changes in the animal’s brain as it learns (or fails) to adapt and becomes refractory to experimentally-induced fear.
The researchers found that germ-free mice had severe learning deficits that prevented them from recognizing that an experimentally-induced fear stimulus is no longer present. The researchers also noticed defects in formation of neuronal connections (dendritic spines) in specific regions of mouse brain as they responded to changes in experimentally-induced fear. The brain chemistry of germ-free mice was also affected with chemical changes resembling those that are associated with the development of autism and schizophrenia. The investigators found that four specific chemicals were decreased in cerebrospinal fluid (a nourishing fluid that bathes the brain and spinal cord) and fecal samples of germ-free mice.
The researchers also investigated if replenishing the normal gut environment within the mice could allow them to overcome learning defects associated with fear conditioning. The studies revealed that such replenishment was successful in rescuing learning deficits only if it was done right after birth. These results revealed that the microbiome is required at an early juncture of life. This finding is of significant interest since psychiatric conditions that are associated with auto-immune disorders also linked to problems in early brain development.
The researchers suggested that such studies could be useful in designing similar studies to establish how gut health influences diseases like autism, Parkinson’s disease, post-traumatic stress disorder, and depression.
Written by Vinayak Khattar, Ph.D., MBA.
- Chu, C., Murdock, M. H., Jing, D., Won, T. H., Chung, H., Kressel, A. M., . . . Artis, D. (2019). The microbiota regulate neuronal function and fear extinction learning. Nature, 574(7779), 543-548. doi:10.1038/s41586-019-1644-y
- News release: https://www.eurekalert.org/pub_releases/2019-10/wcm-gir102319.php
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