How do microbiota determine neuronal function and protect against neurodegeneration?

Project Summary
A fundamental question in neurobiology is how to protect against Alzheimer’s disease. Emerging evidence
reveals a deterministic link between our microbiome, intestine, and neurodegenerative diseases. However, the
molecular basis of the interaction between human gut microbiota and the host nervous system is poorly
understood, largely because the complexity of the human microbiome makes it extremely hard to determine
causal relationships between individual bacteria and neural degeneration. In contrast, C. elegans can be
maintained on single or multiple defined bacterial species, has a relatively simple nervous system, and is
genetically tractable. We are leveraging these strengths to answer the critical question of how different bacteria,
including bacteria isolated from Alzheimer’s patients and healthy adults, influence neurodegeneration.
Specifically, we will 1) determine how bacterially produced vitamin B12 protects against TIR-1/SARM1 induced
neurodegeneration, 2) determine how Buttiauxella protects against neurodegeneration independently of B12,
and 3) identify human bacteria and molecular mechanisms that regulate degeneration in a tractable model
of Alzheimer’s disease. Identifying microbiota, their metabolites and molecular mechanisms that protect neuronal
integrity is essential to understanding how the microbiome influences neuronal integrity and will significantly
enhance our understanding of how to protect against the devastating neurodegeneration that occurs in
Alzheimer’s disease.

Grant Number: 1R56AG086504-01
NIH Institute/Center: NIH
Principal Investigator: Alexandra Byrne