The Gut-Brain Axis

How gut microbes talk to the brain – with thanks to Professor Ted Dinan whose fascinating slide I have borrowed to illustrate the theme of the webinar.

An excellent webinar organised by Yakult in its quest to educate us all about our guts and the importance of feeding them properly. For those of you who would like to follow the whole webinar (there is plenty of science but it is not too challenging) follow this link which will take you both to the webinar and to the speakers downloadable slides. For those of you who just want a flavour, a few brief pointers below.

And just to note that although there has been much focus on the gut over the last ten years, there is still a great deal more that we don’t know than that we do know. So much of what you will find in this webinar is as yet unanswered questions – but none the less interesting for that.

Professor Eric Classen from the Athena Institute VU Amsterdam

• The gut brain axis has only been seriously studied over the last decade; focus has been on the enormous number of nerves contained in the gut, making it ‘our second brain’. Signalling between the gut and the brain is constant.
• Diet is of vital importance in modulating the gut.
• Both the WHO & FAO have linked a wide range of conditions – from specific gut ailments such as IBD and IBS to allergies, cancer and cardiovascular disease –  to gut dysbiosis or disturbance. There is also increasing evidence linking gut dysbiosis to depression and many related neurological conditions.
• It is important to keep the gut filled with good bacteria which have a number of important roles to play. Using antibiotics to clear the gut of bad bacteria clears it of all bacteria leaving the space open for invasion by toxic bacteria.

Professor Jeroen Raes from the Rega Institute at the University of Leuven

Professor Raes’ institute does long term studies of large cohorts with specific focus on gut microbiota.

• They have been finding more and more correlations between changing gut bacteria and a wide range of neurological as well as physiological disease.
• There seem to be strong correlations between the dearth of certain bacteria and depression but there is much work still to be done to prove causality.
• They have also been measuring the quantity of bacteria in particpants’ guts and found wide differences in the weight of bacteria.

Gut bacteria types and B2

• They have found that different people have different types of bacteria. They have identified four types, three of which are healthy, in the fourth (which they have called B2) the bacteria are greatly depleted.
• B2 guts are associated with conditions such as Crohn’s disease and also with depression and poor Quality of Life scores.
• B2 bacteria are often associated with inflammation, depression and neural inflammation – is there a connection?
• B2 guts have less Butyrate – a short chain fatty acid which dampens inflammation. Could that be the connection? They have no evidence as yet – just a supposition.
• B2 bacteria are more common in those who are obese. However, obese people on statins had healthier bacteria than non-statin-taking obese people.  So could statins help to modify the microbiota?

Can you modulate these bacteria to become therapeutic?

• This is all at a very early stage – they need to spend much more time isolating gut organisms and studying them.
• Novel probiotics. Using human fecal material.
• Question? Does the B2 bacteria change in a depressed person if they stop being depressed – they don’t yet know.  But depression is recognised as being multifactoral so it is unlikely just to be the gut.
• How long does it take for a changed diet to affect the microbiota – they don’t really know. The time probably varies from person to person although it could just be a matter of days.
• Should you take probiotics if you are taking antibiotics? For all of the lactic acid commercial probiotics, yes. If you eat a good, low sugar diet your gut will be able to repopulate itself with good bacteria after a course of antibiotics but taking probiotics can only help.
• Colonising the gut with probiotics. If you feed new born babies with probiotics combined with a healthy diet they will colonise in the gut but it is much more difficult to achieve colonisation adults where probiotics are frequently just flushed through.  More research is needed to establish under what cirumstances (probably very personal) probiotics will colonise in an adult.

Professor Robert-J M Brummer  Director Nutrition-Gut-Brain Interactions Research Centre, Pro-Vice-Chancellor, Örebro University

Professor Brummer is a gastroenterologist/psychiatrist so has a dual view on the gut brain axis.

He likes to use the metaphor of a pianist to describe the gut brain relationship – the gut as the piano, the brain as the musician and the scores as the food. This illustrates that when things go wrong it is a functional failure, not an anatomical failure.  If the pianist is unfocused or is tired, the music may not be that good; similarly if the piano is out of tune, or the composition is poor – then again the music will not be good. And so with the gut and the brain.

Connections between the gut and the brain are via:

• the mucosa
• the enteric nervous system
• the blood connections

But there are many mediators which enable these connections – one of which is serotonin. 95% of this serotonin is in our gut, where it is used for general gut functions, but only 3% will reach the brain.  However, that conversion can be adversely affected by inflammation.

Gut microbiota

We know that the gut microbioto build their own ‘ecosystem’.

The first years of life are pivotal in building a healthy gut microbiota.

We know that there is an aberrant microbial composition in many disorders but we do not really yet know what this may mean or what effect it may have on brain function.

Intestinal barrier function

Like a firewall on a computer – the gut barrier is designed to let through what will be beneficial but exclude what could be harmful. Access can be both through the cells of the gut wall but also through the narrow spaces between the cells of the gut wall.

Poor barrier function has been implicated in IBS, Inflammatory bowel disease, aging, stress, metabolic syndrome, obesity and dehyrdation and can result in local immune responses, mast cell degranulation (an allergic response) and activation of the vagus nerve. These may of themselves degrade the barrier function further thus creating more issues.

How do microbes, barrier function, inflammation, serotonin, stress and mental health interrelate?

Inflammation may disrupt the tryptophan/serotinin conversion meaning that less serotonin reaches the brain resulting in depression.

In IBS and IBD there is often poor barrier function. It may be possible to improve this function with probiotics and butyrate.

Other microbial therapies could include antibiotics (if there is an overgrowth of toxic bacteria) and fecal transplants taken from inside the body, not from the waste that is excreted.

Question? How important is the small bowel? Improving the microbial profile in the small bowel may be as important as doing so in the colon.

How do pre and probiotics affect the gut-brain interaction?

• By direct microbe-host interaction or by the compounds they produce?
• What compounds?
• Do they enforce intestinal barrier?
• Or act anti-inflammatory?
• Or improve immune function?

And what effects might this treatment have?

• Attenuating stress impact on gut function
• Improving depression/anxiety
• Modulating satiety
• Preventing/delaying neuro-degenerative disorders, such as Parkinson’s
• But we need to personalize!!!

Don’t forget the diet – the food of the microbiome.

Question?  Will improving a depressed person’s diet improve their depression? It certainly will not do any harm but there are too many other factors to be sure.

Question? Could foggy brain in long Covid be related to the gut? As in all infectious diseases, the barrier function may well have been challenged or damaged by Long COVID – which could have led to brain malfunctions – such as foggy brain.

 

Professor Ted Dinan  APC Microbiome, Cork University

There are  between 1 and 1.5 kilos of bacteria in the gut, comprising over 1000 species. What determines their composition?

• How you are born – vaginal or Caesarean birth – although the gut flora will be very similar by age 3.
• Your diet
• Your geographical location
• Exercise
• Any drugs that you may take
• Stress

Gut microbes communicate with the brain via:

• the vagus nerve
• short chain fatty acids
• tryptophan

Depressed people have very different, usually far less diverse, microbiota than non depressed people.

In a study his group has just carried out with students taking their final exams they found that changing the gut microbiota with diet, pre and probiotics (known as psychobiotics), fecal transplants and some drugs produce a positive effect in terms of:

• reduced stress levels
• improved sleep during stressful periods

When treating with pre and probiotics, multiple strains appear to work better than a single strain especially when combined with a prebiotic.

There are as yet no dose response curves for probiotics so really no idea how many are therapeutically ideal.

Pharmaceutical interventions work much better when the patient has a good diet (and therefore presumably, a healthy gut microbiota).

 

I apologise to the speakers for the rather scrappy notes on their talks and encourage readers who would like to know more to log in to the original webinar. It goes on for 2 hours but is a really interesting listen.