The gut-microbiome is a rich source of metabolic activity. Gut microorganisms that co-exist with the host consume molecules from their environment, catabolise them and release resultant metabolic products. The metabolic actions of the microbiome, and the chemicals that they produce, interact throughout the host system and play a role in the gut-brain axis. Metabolic phenotyping is a powerful tool that is used to comprehensively measure the metabolic content of tissues and biofluids. It can be used to monitor the metabolic products of the microbiome, identify associations with neurodegenerative disease and unravel the mechanistic interactions that occur throughout the gut-brain axis.
We applied metabolic phenotyping platforms to interrogate host-gut microbiome relationships and measured key bioactive co-metabolites and their wider pathways. These pathways were first measured in Alzheimer’s disease and Parkinson’s disease, revealing significant differences in metabolite concentrations when compared with healthy controls. Significant metabolites were reported in indole species and their derivatives, including the neurotransmitter serotonin.
Metabolically phenotyping of germ-free murine models seeded with different gut-microbial cultures revealed that gut-microbial composition significantly altered the peripheral concentration of indoles and serotonin and had influence on organ weight and neurogenesis in the brain.
We conclude that the composition of the gut-microbiome plays an important role in the peripheral bioavailability of key host-gut microbial co-metabolites. In vivo modelling indicates that the host-gut microbiome co-relationship may play a functional role in the gut-brain axis and overall systemic health.