Speaking at the recent Microbiome R&D and Business Collaboration Forum, Anthony Hannan explored research using mouse models for brain disorders, particularly in Huntington’s disease (HD), schizophrenia, depression, and anxiety disorders. He also examined the role of gene-environment interactions involving mental activity, physical activity, stressors, and diet.
Working with a very accurate transgenic mouse model of HD, Anthony said that the approach may “allow us to identify the key molecules for what I would call environment medics “. Ultimately the goal would be to create novel therapeutics, which mimic or enhance the beneficial effects of cognitive stimulation and physical activity.
HD abnormalities extend not just to the HPA axis, but other peripheral organs, tissues, and cells are also disrupted.
So, what might be happening in the gut?
It is well established that there is bi-directional communication between the gut microbiota and the brain. Microbiota also play an important role in regulating many other organs.
16S amplicon sequencing of the faecal samples from HD and wild-type mice revealed, strikingly, that the Huntington’s disease mice had an altered microbiome in their gut. This alteration occurred even though the mice were in the same caged environment with the same diet. Additionally, the changes occur at a very early age before the onset of overt motor symptoms. Further research showed that there is gut dysbiosis in clinical Huntington’s disease as well.
“This is the first evidence that we showed, that gut dysbiosis and indeed occurs in Huntington’s disease”
Follow-up studies in both mice and humans included working with shotgun sequencing. By going right down to the level of bacterial species, it is possible to establish that the onset of gut dysbiosis is present by 12 weeks of age. In addition, there is a correlation between altered metabolites in the blood and the metagenomic analysis of the bacterial composition of the gut microbiota.
New research is trying to establish how the gut might signal to the brain and other organs and how this contributes to the pathogenesis of Huntington’s disease.
Anthony Hannan is head of the Epigenetics and Neural Plasticity Laboratory at the Florey Institute of Neuroscience and Mental Health in Australia.