Exploring the gut-brain axis in neurodevelopmental disorders

Posted 30th March 2020 by Joshua Sewell

In the last decade, research has well established (relatively speaking) the impact of gut microbiota on host physiology and behaviour. We know that the gut and the brain communicate bidirectionally. The gut-brain axis includes nerval, endocrine and immunologic pathways. What is less well established is whether alterations in gut microbial composition can affect brain structure and function in neurodevelopmental disorders.

ADHD and the gut

Various neurodevelopmental disorders like attention-deficit/hyperactivity disorder (ADHD) implicate altered brain structure and function. There is a definite link between brain symptoms and intestinal tract problems for conditions such as autism. However, we know little about the relationship between ADHD and the gut microbiome.

Vagal nerve activity is a potential pathophysiologic mechanism for ADHD, which is partially driven by the triggers by the commensal microbiota via cells in the gut epithelium. The gut microbiome could also have an important role to play in ADHD by affecting the synthesis and metabolism of neurotransmitters and their precursors. 

If we can establish a clear pathway between the gut and ADHD symptoms, then it could suggest promising directions for future therapies. We currently treat ADHD primarily with medication. However, dietary interventions would be a promising alternative to pharmacological treatment.

Is there an ADHD ‘microbiome’?

For a pilot study, we transplanted bacteria from human donors with and without ADHD symptoms into young, male, germ-free mice. We were interested in discovering if the mice display any signs of ADHD differences in the microbiome or the brain merely from the transplantation of bacteria.

We started by reviewing if we could find any pattern in the mice microbiome and distinguish from which group the mice received microbiota. We saw a clear separation between the groups. We further hypothesized that the gut microbiota from each human group would differentially modify brain function or structure when transplanted into mice. We found this to be a correct hypothesis. Additionally, the mice that received the microbiome from ADHD patients showed changes in anxiety measures.

Comparing the brain structure and function

We would like to see if there is a correlation with the abundance of specific bacteria and the observed structural and functional changes. For some regions, we saw a difference in grey and white matter depending on which transplant the mice received. We also found some particular bacteria correlated with these differences in brain and behaviour. Even with the findings we have, it is impossible to say anything about causal relationships. We don’t know whether these are the only bacteria that could have this effect nor how they exactly altered the systems. 

In the future, it would be ideal to make the research more related to the human disorder. We could include behavioural tasks that are very specific to ADHD and see if we can influence the microbiome using more specific analysis techniques. Or, by using a probiotic or some other treatment and changing the microbiome so that the brain differences disappear.

Sarita Dam is a PhD candidate in Translational Psychiatry at Radboud University Medical Centre Nijmegen, The Netherlands.

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Tags: gut microbiome, gut microbiota, gut-brain axis, microbiome, neurodevelopment disorders