McMaster University

Forsythe Lab

Scope of Search

Understanding the microbiota-gut-brain axis

1) Mechanisms of microbiota-gut-brain communication

There is now good evidence that specific nonpathogenic intestinal microorganisms can signal to the brain as part of the so-called microbiota-gut-brain axis. We are exploring the immunomodulatory and neuroactive properties of gut bacteria with the aims of:

Understanding the relationship between the gut microbiota and changes in brain and behaviour in response to stressors including social defeat and circadian rhythm disruption.

Determining how modulating the gut microbiota with antibiotics or probiotics influences environmental stress induced changes in brain chemistry and behaviour

Identifying the role of the nervous and immune system in mediating communication between gut microbiota and the brain.

PNEfigure

Effect of chronic social defeat on structural changes in the microbiota and association with behavioral deficits. (A) Taxonomic distribution at the phylum and class level of fecal samples derived from the control and defeated groups. (B) Statistically significant changes in OTUs belonging to either the Firmicutes or Bacteroidetes phyla, displayed as fold change in defeated mice relative to the control group. (C). Procrustes plot comparing aggressor interaction behavioral data and the microbiome profile (unweighted unifrac distances) of each mouse from control and defeated groups. Lines connect the behavioral and phylogenetic data of a specific sample.

 

2) The effect of antibiotics in early-life on brain function and behaviour

The objectives of this project are to determine the long-term impact of early-life disruption of the gut-microbiota, by clinically relevant doses antibiotics, on brain chemistry and behavior related to anxiety and social interaction; to delineate immune mechanisms linking the altered microbiota to behavioral changes; and identify potentially novel components of the microbiota-gut-brain axis related to antibiotic effects on brain function and behavior.

Together with our collaborators in Israel and Chile we are addressing these issues by:

Determining the relationship between microbiota composition, gut neurophysiology and brain and behavior changes in response to early life exposure to antibiotics.

Identifying the role of CD4+ T helper cells in mediating gut-brain communication in response to early life exposure to antibiotics.

Utilizing a Drosophila model and comparative physiology to identify novel mechanisms of microbe- gut -brain communication in relation to antibiotic effects.