Serotonin, tryptophan metabolism and the brain-gut-microbiome axis

Aug 1, 2014Behavioural brain research

Serotonin, Tryptophan Processing, and the Interaction Between the Brain, Gut, and Microbes

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Abstract

The gut microbiome may play a critical role in regulating the brain-gut axis by influencing serotonin production.

Serotonin acts as a key neurotransmitter in the communication between the brain and the gastrointestinal tract.
The gut microbiome may affect tryptophan metabolism, which is important for serotonin synthesis.
Behavioral patterns associated with gut microbiota overlap with those requiring proper serotonergic function.
Differential microbial colonization before adulthood may impact the development of the serotonergic system.
In elderly individuals, decreased gut microbiota diversity and stability could be linked to serotonin-related health issues.
The gut microbiota may regulate serotonin synthesis by controlling tryptophan metabolism and influencing neuroactive metabolite production.

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The brain-gut axis is a bidirectional communication system between the central nervous system and the gastrointestinal tract. Serotonin functions as a key neurotransmitter at both terminals of this network. Accumulating evidence points to a critical role for the gut microbiome in regulating normal functioning of this axis. In particular, it is becoming clear that the microbial influence on tryptophan metabolism and the serotonergic system may be an important node in such regulation. There is also substantial overlap between behaviours influenced by the gut microbiota and those which rely on intact serotonergic neurotransmission. The developing serotonergic system may be vulnerable to differential microbial colonisation patterns prior to the emergence of a stable adult-like gut microbiota. At the other extreme of life, the decreased diversity and stability of the gut microbiota may dictate serotonin-related health problems in the elderly. The mechanisms underpinning this crosstalk require further elaboration but may be related to the ability of the gut microbiota to control host tryptophan metabolism along the kynurenine pathway, thereby simultaneously reducing the fraction available for serotonin synthesis and increasing the production of neuroactive metabolites. The enzymes of this pathway are immune and stress-responsive, both systems which buttress the brain-gut axis. In addition, there are neural processes in the gastrointestinal tract which can be influenced by local alterations in serotonin concentrations with subsequent relay of signals along the scaffolding of the brain-gut axis to influence CNS neurotransmission. Therapeutic targeting of the gut microbiota might be a viable treatment strategy for serotonin-related brain-gut axis disorders.

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Serotonin, tryptophan metabolism and the brain-gut-microbiome axis

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