Neurodegenerative diseases, such as Alzheimer’s Disease (AD), are characterized by progressive deterioration of cognitive functioning observed mainly in older individuals beyond what is expected from normal ageing. Neurodegeneration should be viewed as a holistic mechanism, and this view is supported by evidence of changes in central, autonomic and enteric nervous system activities observed in neurodegeneration.

The role of the enteric nervous system in neurodegeneration is only now starting to unfold, with the gut microbiome (the microorganisms living in our gut) playing an integral part via its local interaction with the enteric nervous system, as well as direct interaction with the central nervous system through the vagus nerve, neuroendocrine and metabolic pathways. The communication between these spatially distinct systems is achieved through a bidirectional gut-brain axis connection, which also suggests that our gastrointestinal contents may influence cognition. The gut microbiome has been linked to neurodegeneration, with a growing body of evidence from clinical and experimental data supporting that the disruption in the balance of microbial populations, such as increase in pathogenic bacteria, is a key factor in neurodegeneration. This is facilitated through their interaction via the microbiome-gut-brain axis.

The project is based on the hypothesis that the gut microbiome plays a driving role in this holistic effect of neurodegeneration, through gut-brain axis communication.

Our main objective is to investigate whether administration of probiotics to patients with mild AD reduces neuroinflammation, improves cognitive functioning and modifies neurophysiological measures, compared to a patient group that receives placebo (no active probiotics). We hypothesize that, following probiotic administration, we will see a reduction in specific blood inflammatory markers, which will correlate with positive changes in neurophysiological activity and cognitive test scores, in the probiotics but not the placebo group. We will also study the microbiome composition of the participants to identify whether positive changes are related to specific microbiome profiles.

This work is supported by an Alzheimer’s Association Grant (AARG-NTF-22-928616).