Hitting a nerve: The link between vagal stimulation, the gut and depression

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Probiota 2020 will take place at the Clayton Hotel Burlington Road in Dublin. ©iStock/

Recognising biologically similar pathways in those with depression could result in a precision led approach that points people towards more effective methods to address the neurological condition.

Speaking to NutraIngredients, Dr John Bienenstock believes that out of the large and diverse group categorised with depression, it may be possible to identify smaller groups with something biologically in common.

“Depression comes in various forms and represents a spectrum of disorders and it is not clear if they are simply variations of a single disease process or separate entities identified clinically by the symptomatology,” says Dr Bienenstock.

“Indeed, one might be able to say that this issue is common to most chronic diseases in which the etiology is unknown eg. autism spectrum disorders, etc.”

Dr Bienenstock’s interest in depression brings into the conversation the role of the gut microbiome, specifically the gut-brain axis and the vagus nerve – the main neural connection between gut and brain.

Speaking ahead of his presentation at Probiota, held this year in Dublin, Ireland, Dr Bienenstock comments on the comparisons between the gut-brain axis’ role in not only depression but other neurological conditions such as multiple sclerosis, Parkinson’s and stroke.

“Clearly there are parallels between many of the experiments shown in gut microbiota having an effect in these diseases,” says Dr Bienenstock, who is director of the Brain-Body Institute, McMaster University and St. Joseph’s Healthcare in Hamilton, Canada.

“This would certainly be true for some of the experimental models of those conditions but there are some hints in clinical conditions including Parkinson's disease. 

“The extent to which some of these changes may be due to the gut microbiota influence on immune function and thereby regulation of unknown causes of inflammation which in turn may be deleterious in those conditions is not known but it is a reasonable postulate.”

What happens in vagus…

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Dr John Bienenstock, director of the Brain-Body Institute at St. Joseph’s Healthcare Hamilton. ©John Bienenstock (Will Chu)

The importance of gut-brain communication via the vagus nerve and what it means for the treatment of depression will be a focus of Dr Bienenstock’s presentation.

Other areas of discussion include the latest research that demonstrates how communication via the gut-brain axis results in beneficial bacteria modulating behaviour and brain neurochemistry.

But as Dr Bienenstock points out firm conclusions are hard to come by in this area with human studies limited by relatively small sample numbers and non-control for unusual diets, antibiotics or antidepressants.

“I agree that human studies so far have not provided firm conclusions and are tantalising,” he says.

“Animal studies are better science based but inevitably the question remains as to whether they are generalisable.”

Nevertheless, the progress made, and knowledge gained in this area is all the more impressive especially considering the word ‘microbiome’ was unheard of a decade ago.

Researchers already know gut microbiota can stimulate neurotransmitter and neuroactive compound production to modulates bacterial growth

Now, Dr Bienenstock thinks the next step is to discover how these microbe-derived molecules can interact with the human central nervous system, and whether that alters a person’s behaviour or risk of disease.

His talk touches upon this evolution in knowledge of the gut microbiome, specifically the microvesicles shed by gut luminal bacteria that activate the enteric nervous system.

Through a nicotinic synapse, this in turn stimulates the vagus, promoting activation of specific brain regions.

Dr Bienenstock will also discuss how oral selective serotonin reuptake inhibitors (SSRI) lose their behavioural effects in vagotomised mice emphasising the importance of the vagus in developing new anti-depressive therapies.

Looking towards the future

In speaking about new treatments for depression, Dr Bienenstock comments on the body of microbiome research that cannot identify a single species responsible for the neurological effects.

Indeed, recent research points to the overall ratio of the different microbial families as more significant. So, does he see any implications to this observation in the creation of new treatments for depression?

“It is true that it appears that no single species of bacteria is responsible for the observed effects in the gut-brain axis,” says Dr Bienenstock.

“Therefore, it is likely that multiple strains may be necessary to obtain maximum effect specially to establish communities of bacteria producing a specific range of molecules necessary for beneficial host action. 

“However, it is not impossible that a single strain may produce sufficient biological effects especially if taken in sufficient amounts,” he adds.

“Since these beneficial bacteria on the whole do not colonise, it is likely therefore that they would have to be taken on a long-term basis if positive effects once obtained were to be maintained. 

“Of course, we have no information as to such long-term treatment effects even in experimental animals.”

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The rapidly evolving universe of probiotics, prebiotics and the microbiome will be propelled into the new decade at the upcoming Probiota 2020​​ summit in Dublin on February 10-12.

From advances in microbiome research, to start-up game changers, key market stats, crucial clinical science and regulatory knowledge, attendance is a must-have for those in the prebiotic, probiotic and microbiome sectors. 

Will you be joining your peers in one of the world’s greatest cities?