Project 3: Mechanistic Studies on Role of Microbiome in Models for AD

Utilizes preclinical models to measure disease-specific outcomes across stages of Alzheimer’s Disease

Aims:

  • Establish and define gut-microbiome-brain connections in preclinical models of AD.
  • Transplant human microbiomes from AD patients and controls into mice to characterize functional contributions to disease.
  • Test if defined human microbes and specific metabolites modulate symptoms and pathology in AD mouse models

Overview of the gut microbiota-brain axis

Bidirectional communication between the gut microbiota and the central nervous system is mediated by several direct and indirect pathways of the gut–brain axis. Most of the information on host–microbiota interactions, and thus the data presented in this figure, is derived from studies in animal models where researchers can effectively control the environment of the test animals.

Microbiota & microbial- derived molecules modulate behavior & nervous system function

Microorganisms can induce host production of metabolites and neurotransmitters that mediate gut–brain signalling and can produce some of these neuroactive compounds themselves. Microbial-derived molecules signal to the brain via neuronal pathways of the vagus nerve or modulate the immune system.