We are what we eat? The link between gut microbiota and neurological disorders

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Picture: McGill University

Gut microbiota is an ecosystem of millions of microorganisms that are found in vast quantities in the human intestine. They are essential for effective metabolism, gut hemostasis, as well as the breakdown and absorption of nutrients. Gut microbiota is acquired as early as birth and is largely influenced by our diet throughout life. The dynamic mix of microorganisms that make up our gut microbiota is also modulated by prebiotics, probiotics and other food additives. 

Changes in the composition and diversity of the microorganisms that make up our gut microbiota have previously been correlated with several neurological disorders, namely autism spectrum disorder (ASD), depression, schizophrenia, psychotic disorders and anxiety. The prevailing hypothesis is that alterations in gut microbiota affect brain function through a bidirectional axis of communication, called the ‘gut-brain axis’ (GBA). When changes in the diversity or composition of the microorganisms occur, they change the physiology of the gut lining, which, in turn, influences both our immune system and our brain via the GBA.

The exact mechanisms that allow crosstalk along the GBA are complex and are not fully understood but are thought to be a part of a comprehensive network of both the endocrine, immune and autonomic nervous systems. Several gut-brain communication pathways have been identified include the vagus nerve (which provides a direct connection between the gut and the brain), as well as the production of bacterial metabolites which communicate with cells in the blood-brain barrier (and consequently may influence brain function). 

Adapted from: Campbell, A.W. et al. (2014). Autoimmunity and the Gut. Autoimmune Dis, 152428.

Converging evidence from early animal studies suggest that a stable gut microbiota is pivotal for a healthy gut physiology. Healthy gut physiology, in turn, allows for appropriate signalling along the GBA which does not lead to behavioral or neurological disorders (as seen in the left hand side of the image). When gut microbiota undergo drastic alterations in its composition (also called intestinal dysbiosis), it may adversely influence gut physiology and consequently lead to inappropriate signalling along the GBA. This disturbed signalling may result in the onset of various neurological disorders (right hand side of the image). 

A recent review article by Johnson (2020) summarized the specific gut microbiota changes that occur in various neurological disorders. For example, children with ASD were found to have different quantities of various gut microorganisms; Bifidobacterium, a major genera of intestinal bacteria, was found in smaller amounts in children with ASD. Conversely, other genera of bacteria, namely Sutterella and Clostridium, were found in increased abundance in children with ASD, compared to healthy individuals. Clostridium was also found in higher quantities in adults with Schizophrenia, coupled with increased quantities of Collinsella and reduced quantities of Roseburia and Blautia, compared to healthy controls. 

Therapeutics:

The strong correlation between neurological disorders and disturbance in gut microbiota may represent a new target of intervention. Therapeutic techniques that treat dysbiosis, namely probiotic treatment and fecal transplant therapy (where a patient receives feces containing gut microbiota from a healthy donor), are gaining attention in the scientific community. A recent study (Kang et al., 2019) found beneficial, long-term effects in 18 children with ASD who underwent fecal transplant therapy. The results suggest that after 8 weeks of therapy, their behavioural ASD symptoms and other associated intestinal symptoms (such as constipation, indigestion and abdominal pain) were reduced by 80%. Furthermore, symptom improvements continued for another 8 week period.

Further translational evidence from long-term and randomized trials are needed to test the efficacy of these therapeutic techniques. Yet, gut microbiota and the GBA are at the forefront of the medical research community, as they have promising potential to complement, or even undermine, some of the conventional treatments for neurological disorders. 

Studies:
Johnson, K. (2020). Gut microbiome composition and diversity are related to human personality traits. Hum. Microbiome J., 15, 100069. https://doi.org/10.1016/j.humic.2019.100069

Kang, D. et al. (2019). Long-term benefit of Microbiota Transfer Therapy on autism symptoms and gut microbiota. Nature Sci Rep, 9, 5821. https://doi.org/10.1038/s41598-019-42183-0

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