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Pan European Networks: Science & Technology





he population of microbes that live inside the intestine are

collectively known as gut microbiota. It is estimated that

there are some ten trillion micro-organisms inside every

person.While around one-third of these micro-organisms are

common to us all, the remaining two thirds are unique to each

individual. However, despite the resident specificity of microbiota,

they all perform the same essential physiological functions, such

as ensuring proper digestive function and playing an important

role in the immune system. Despite the universal acknowledgement

of the importance of our gut microbiota, there is still a great deal

to be understood.

To address this dearth in knowledge, more and more studies are

exploring the microbiome-gut-brain axis, which refers to the

biochemical signalling that occurs between the gut microbiota,

endocrine, immune and enteric nervous system (ENS), and the

brain. Because of the relative infancy of the field, large knowledge

gaps still exist. Studies have, however, begun to shed light on the

important role gut microbes play in human development,

maturation and adulthood.

The complex nature of commensal relationships

For the past decade, three researchers from the Brain-Body

Institute (BBI) at McMaster University (Hamilton, Ontario, Canada)

have collaborated on a range of projects that seek to understand

more about the microbiome-gut-brain axis. Professors John

Bienenstock, Paul Forsythe and Wolfgang Kunze have dedicated

their studies to uncovering how commensal bacteria affect the

function of the ENS and the brain, in addition to exploring the

pathways that may be involved in their interactions. Indeed, their

major focus is on delineating the mechanisms and pathways of

communication between gut microbes and the host, findings that

will have significant implications for understanding immune

disorders, as well as neurodevelopmental and mood disorders.

One study, funded by the US Office of Naval Research, led by

Bienenstock, seeks to understand the positive effects on negative

responses to environmental stressors. More specifically, the

researchers are aiming to identify the pathways and specific

molecules involved in human mental distress. Using mouse

models, the team applies molecular methods to investigate how

the complex relationship between the gut microbiome, the brain

and behaviour are affected by changes to each system, a

combination, or all of them. Ultimately, their findings could enable

clinicians to maintain or restore normal brain function. “The

molecules involved could be mimicked, or synthetic molecular

analogues could be developed as drugs,” elaborates Bienenstock.

“It may well be possible to use the specific bacteria – or clusters

of developed bacteria – to effect changes which promote

beneficial central nervous system (CNS) pathways.”

Making the vagus nerve’s role less vague

The team has already achieved significant results and led the

discovery that the vagus nerve may be involved in the important

transmission of information to the brain from the gut bacteria.

Indeed, the team has used these findings to treat anxiety and

depression-related behaviour in mice. The US Food and Drug

Administration (FDA) approves vagal nerve stimulation to treat

depression. It is clear that commensal bacteria in the intestine

can affect the ENS and the CNS, but the exact way in which this

manifests is not yet known. In unravelling this information, the

team has the aim of extrapolating and translating these data into

clinical treatments for psychiatric disorders.

Many findings have been documented over the last ten years,

reporting the spectrum of the team’s research endeavours. One

key finding has been the discovery that bacterial microvesicles

shed from a commensal bacteria known as JB-1 are able to

mediate many of the immunological effects of the parent whole

live bacteria, and have found a component of those bacteria that

replicates many of those effects. “The exploration of microbial

Researchers at the Brain-Body Institute at McMaster University investigate

how commensal bacteria affect enteric nervous system and brain function.

Their findings could significantly impact healthy gut and brain function

Left to Right: John Bienenstock, Paul Forsythe and Wolfgang Kunze