Have you ever wondered if food affects your mood? If you eat a diet that is not diverse will you feel more anxious and depressed? Does a natural birth matter? I had the pleasure of speaking with Prof Ted Dinan about the gut-brain connection. Ted Dinan is one of the four leaders in this space. He is a professor of Psychiatry and he is also a principal investigator at APC Microbiome Ireland. They work on the microbiome and he teaches Psychiatry to medical students. Read on to see if antidepressants alter the gut microbiota if cesarean births impact gut health if wheat affects the brain and if obesity can be transferred from one person to another.
How Did You Stumble Upon The Idea of Gut Health?
My background is in Pharmacology. Years ago when I went to Trinity College, another Professor told me about the gut-brain axis and persuaded me that it was an important area for:
-Understanding various physiological processes
-Understanding gastrointestinal diseases such as IBS
I became interested in it but it was never my primary area of research. When I returned to Cork 15 years ago, I started collaborating with the microbiology team. This was the time when they started talking about microbes and the gut-brain axis. When I was doing research 30 years ago, it was the brain & gut and the way they connect (we did not include microbes!) But when I started collaborating with the microbiologist’s, they were interested in bacteria and viruses within the gut. We have now come to understand the Gut-Brain Microbiome Axis.
I coined the term Psychobiotics a few years ago. Psychobiotics are bacteria which when we introduce in adequate amounts have positive mental health benefits. My interest is in modulating the microbiota to treat psychological and gastrointestinal illnesses. Within the average adult intestine, we have 2 kilograms of bacteria. Most of our bacteria are in the large intestine. Those bacteria produce a raft of molecules that our brains and other organs require. This means that we are very dependent on gut microbiota.
It is possible to raise animals who have no microbiota. When you do this you will see that the brain does not develop normally. With that, social functioning (which is a very important part of physiological illnesses) is abnormal in animals who don't have a microbiota.
Psychobiotics are just one way of modulating the microbiota.
How Can We Impact The Microbiota To Improve Mental Health?
Psychobiotics are one way to potentially impact the microbiota. The main Psychobiotics are Bifidobacteria and Lactobacilli. Many strains of bacteria are claimed as Psychobiotic but in fact, don't have adequate data behind them at all. One of the big problems in this area of research is that a lot of claims are made saying that certain bacteria are probiotics. The European food safety authority has largely banned the use of the term probiotic. This is because it implies that bacteria can improve health. Many of these claims have NO evidence that they improve health at all. Be mindful of where you get your data from!
According to European Standards, what is the protocol for validating a claim?
If you are going to make a claim for IBS or Anxiety you need to produce double-blind, placebo-controlled studies, demonstrating efficacy. Most companies that have submitted data for use of the term “probiotics,” have had their application rejected. This was because the science wasn't up to an adequate quality. The Pharmaceutical industry is used to doing high calibre studies, but the food industry, on the other hand, has no tradition completing sophisticated research.
A big reason for this is that the profit margins for a new drug are very high. If you get that drug out you can make a lot of money fairly quickly.
The margins in the food industry can be very small. The food industry is often relaxed and they don't feel safe investing a lot of money into a premium product that they may not get their money back on. Many food companies have started doing higher-level research on their natural products. They will have health benefits but people will also be paying a higher price for them.
A LOT of patients who are depressed and have anxiety do not like taking antidepressants. They would rather cognitive behaviour therapy but it is not always readily available and it can be expensive. If there were nutritional components that would treat depression and anxiety it would give a radical improvement in the choice of therapy for patients. It would also give psychologists and psychiatrists an exciting and new modus operandi in treating psychological disorders. This is why there needs to be a lot of data-driven research before these claims are made.
The Connection Between The Gut And Brain
The connections are gradually becoming understood. A few years ago understanding was quite limited, now we do know certain pathways that are HIGHLY important. There are a few very important routes:
The Vagus Nerve- It is a bidirectional root of communication because:
Signals from the gut >>>> can go to the brain>>>and from the brain, they can go to the gut
There are certain bacteria that seem to entirely use this route of communication. Certain bacteria will NOT communicate with the brain if the vagus nerve is cut.
Production of Short Chain Fatty Acids- Bacteria within the intestine is capable of digesting fibre and producing short-chain fatty acids. Examples would be molecules such as Butyrate, Propionate, and Acetate. These can get into the bloodstream and they can influence organs including the brain.
Production of Tryptophan- Tryptophan helps the body produce serotonin. Our brains have very limited capacity for storing tryptophan and we need a constant diet supply of it. We do not store it in high quantities. We need it to be available to cross the blood-brain barrier. That tryptophan comes largely from 2 sources:
- Production of Molecules Within the Immune System- The immune system is active throughout the body but there's a very complex immune system in the gut. And these immune molecules travel from the gut to the brain and influence brain activity.
They may all be working in parallel to help deliver messages to the brain and vice versa.
How Do Bacteria Produce Tryptophan?
The pathways within the bifidobacteria have been studied and they seem to be the one bacterial source of tryptophan. There may be other bacteria that are capable of this that have not been researched yet.
In babies there are very high levels of bifidobacteria but as we age these levels decline.
Bifidobacterium longum 1714 is the strain that has been studied for anti-anxiety effects. Ingesting it in large amounts promotes this effect. It may or may not be because it’s producing tryptophan. BUT If you introduce these bacteria, the levels of tryptophan in your bloodstream do increase.
How Do These Compounds Alleviate The Symptoms Of Stress And Anxiety?
We know of two important mechanisms:
Promoting normal serotonergic transmission: Serotonin regulates sleep, appetite, sexual behaviour, and mood. This seems to be one important way that these bacteria can influence our brains.
Capacity to dampen down our stress responses: The core stress axis in humans is the Hypothalamic–Pituitary–Adrenal Axis. Many people are familiar with cortisol. Cortisol is the main stress hormone. When you experience stress your cortisol levels increase. They also may stay at an elevated state for an extended period of time. We do know that certain bacteria (Bifidobacteria being one) are capable of dampening down the cortisol response. And this seems to be VERY important in terms of the anti-stress effect.
Cortisol is a very important hormone in our bodies and does a lot of important things but excessive cortisol production is damaging to our health.
One example of this is Cushing's Disease. A pituitary tumour secretes an excessive amount of cortisol and it has a very damaging effect on the heart and bodily functions. Even in depression, we know that cortisol levels are high and people can be depressed for an extended period of time. Cortisol does have a negative impact. We know that people who have suffered from depression are more likely to suffer from a heart attack. That is probably largely driven by high cortisol levels.
There are a lot of studies following depressed people over a period of time and they have far more heart disease than the general population. When we use something like a psychobiotic, it gives people a greater capacity to deal with stress.. Cortisol is damaging to many parts of our body but mainly our cardiovascular system.
When I was sent for cortisol testing when I had depression, it came out as being elevated throughout the entire day. That's how they determined that I had an issue- Kriben Govender
Are Babies Born By Cesarean Section At A Greater Risk For Poor Gut Health?
We have been following people that have been born by cesarean vs vaginal and it has now been determined that the microbiome develops differently with those two scenarios. If a baby is delivered vaginally, they come through and pick up lactobacilli from their mother and that becomes the dominant microbial species for the first year or two. If the baby is delivered by Cesarean Section, they have found that the bacteria in the microbiome is from the mother's skin and for the first 3-4 years that baby has a very different microbiome.
That is relevant because C Section rates are increasing in most countries. The World Health Organisation recommends C Sections rates of about 12% yet most countries are WAY over...
Brazil- 50% Cesarean Section
China- 90% Cesarean Section
When you have a baby born by C-Section they are more likely to develop asthma and other allergies than babies that we were delivered vaginally. Aside from that, many babies that are born by C Section are also exposed to more antibiotics earlier on. Antibiotic exposure early in life greatly increases the risk of obesity in adulthood. So a baby who was born by C Section, and has had heavy use of antibiotics is far more likely to end up as an obese adult.
Study: Adults that were born by C Section vs Adults that were born vaginally:
It was found that adults born by C Section have consistently higher stress responses. It is not a massive difference but it is a definite difference between the two. The first 3-4 years are pivotal to stress responses. The stress responses have developed in a slightly different manner and these differences are persistent into adulthood. There ARE times when a C Section is needed but we need to evaluate why these are increasing within the past decade.
We know that there's a lot of inappropriate antibiotic use in adulthood. Exposure to antibiotics in adulthood does increase the number of depressive episodes in the months following antibiotic use. The antibiotic greatly affects the microbiome in the next 8-12 weeks. There isn't a permanent effect of antibiotics in adults. BUT if a baby before the age of a year has 2 or more courses of antibiotics, that alters their microbiome. The evidence suggests that it greatly increases the risk of obesity. Which is a major health issue in the west?
Is There Any Research Suggesting That Antidepressants Impact The Microbiome?
There is a paper coming out shortly that will show the impact of antidepressants on the microbiome. We have found that commonly used antidepressants such as Fluoxetine (Prozac) radically alters the microbiome. Another substance that is used in mood disorders is Lithium. It is mostly used for people that have Bipolar Disorder. But it is also used for severe depression. This also alters the microbiome. Another one is Olanzapine and it is used to treat Schizophrenia BUT it can be used for depression as well. This had a DRAMATIC effect on the microbiome. All of the data suggests that the dramatic impact is the reason why Olanzapine is associated with a lot of weight gain. There is a big increase in Firmicutes and a decrease in Bacteroidetes when Olanzapine is in your system.
Another study: If you take a germ-free animal that has no microbiome, Olanzapine shows no weight gain at all. It only causes weight gain when there are microbes in the intestine.
It’s been known for a decade that obese people have more Firmicutes and less Bacteroidetes. If you do a transplant from an obese person into a lean person, the phenotype of the lean will alter and that lean individual will become obese. When you take the microbiome of a lean person and put it in the microbiome of the obese person they will tend to lose weight. Bariatric surgery (which is used for treating obesity) alters the microbiota. One of the reasons why the surgery works so well is that it alters that structure.
The Rise of FMT (Fecal Microbiota Transplantation)
These transplants have been used more and more within recent years. Gastroenterologists are aware of the major benefits. It is effective in up to 90% of individuals. But as with everything, there are some hazards:
-If the donor is obese, you may be transferring an obese phenotype to the recipient.
-If you take the microbiome of a depressed patient and you put it into a rat, that rats behaviour does alter radically. On the other side of this, if it gets the transplant from a healthy patient then it doesn’t change at all. What I always say to gastroenterologists is when they are assessing the donor makes sure that they don't have HIV, HEP C, and make sure that they are free of psychiatric illness. You could end up transmitting psychiatric phenotypes from the donor.
As these treatments become more prevalent, this is a great warning for the practitioners out there that are engaging in this type of treatment. They need to screen the donors to make sure they are free of these. They may not regard the presence of depression in the donors as important to what they are doing.
What Inspired You To Co-Author A Book?
I have a passion for the gut-brain microbiota axis and the potential of that area to deliver improved treatments with patients with mental health problems. When our article came out about psychobiotics, it struck a chord with the general population. We wanted to make it a readable book that was geared towards the public and wasn't making outlandish claims. We wanted to give people advice about what to eat, what not to eat, and other ways to improve mental health. The book is called The Psychobiotic Revolution.
There was a paper that was delivered to a London audience back in 1910 by a Psychiatrist and he was suggesting that bacteria were a way of treating melancholic depression. This was AMAZING at the time. The use of fermented foods was being advocated at the time but it was certainly a revolutionary idea that people would use bacteria to treat depression. Although, my view is that these bacteria will impact the milder forms of depression rather than the more severe melancholic depression. When you see people that have an extreme form of depression they are happy to receive any form of antidepressants. If you have a milder form of depression, you usually do not want to take an antidepressant if you don’t have to.
If we had more naturally occurring approaches such as psychobiotics (they could be prebiotics as well) then it could give the people with mild forms of depression a different option. If you suffer from depression, go on a Mediterranean type diet with a lot of fruit and vegetables. Take your protein in fish and chicken, keep red meat to a minimum and a MAX at once a week. Red meat is not good from a mental health perspective. Do not eat processed foods, trans fats and have aerobic exercise on a regular basis (5 days a week for 30-40 minutes.) This is the most potent antidepressants available. It also has a great impact on the gut microbiome.
FOS GOS- Are anti-anxiety but I always stress that the best delivery system is GOOD FOOD. Looking at prebiotics, Inulin is one of the most widely studied prebiotic. It is in high concentration in things like celery, bananas, artichokes, and onions. There are a lot of vegetable sources that have inulin.
Inulin is fibre and fibre is good for your health but not all fibre is prebiotic.
Fibre is good for our mental health and prebiotic fibre promotes the growth of good bacteria. They have a bifidogenic effect on our gut. Prebiotics cannot be metabolized by us. Certain bacteria and bifidogenic bacteria metabolize it for us! The prebiotics stimulates the growth of that bacteria since we need it to metabolize it.
What does the roadmap for mental health services incorporating gut-brain research like psychobiotics in a clinical setting look like?
Right now any interest in this with Psychologists and Psychiatrists is very limited. Nutritional Psychiatry is at a very early stage of development. I think that Psychologists should be looking at the diet of their patients. And most of them do not. Everyone that comes to see me for depression, I do give dietary advice. It is not the way things are generally. We need to educate health care professionals. We need to incorporate information about diet in our training and education for Psychiatry.
Do grains such as wheat have an impact on the brain?
Ingesting grains DOES promote the growth of new bacteria. There was a study done that was looking at the intake of fibre. This showed taking in a lot of fibre reduced risk of things such as Alzheimer's. The fibre intake in most developed countries is WAY below what it should be. We should be taking 30 grams of fibre per day - most people are taking around 12g. There are a lot of people out there with fad diets and they come out and say they are allergic to this, that, and the other thing. They may eliminate things that might not be good for their health in the long run if they are persistent long term.
There are a lot of things like the FODMAPS and GAPS diets that are supposed to only be used for a short period of time to heal and then go back to your normal routine. But many people stick on these diets which may not work in their favour. Make sure to test the waters before you eliminate something out of your diet for an extended period of time.
Is there any link between stress and IBS?
Most sufferers from IBS will tell you that their health is worse when they are under periods of stress. Half of the patients diagnosed with IBS in our clinic also have a depressive illness. So they have:
IBS + Depression
IBS + Anxiety
Even though some do not have a psychiatric illness, stress does make their symptoms worse. Try to eliminate most of the stress from your day to day life. Exercise and meditation are two powerful things to combat stress.
Are there any Psychobiotic strains that you recommend people start with?
As far as IBS is concerned, there are many strains out there that have placebo-controlled studies demonstrating efficacy. One strain being 35624, there is very good evidence there for the symptoms of IBS.
When it comes to depression and anxiety, there are studies out there but they are more limited. I would suggest starting with your diet first rather than taking a probiotic. We need to look at the intake of the inulin fibre and increase it. This would be the first way to improve your mental health.
“A good diet is the best way to deliver nutrients to the brain.”
We have been so conditioned to look for a supplement to help us instead of stepping back and looking at where we can improve our diet. Get a good foundation for your diet and lots of fibre. I take in a lot of fibre and eat a lot of fermented food to feel the best I can feel.
What is the one thing you can do to improve your mental health?
AEROBIC EXERCISE. It’s the most important thing.
There are many things that you can do to improve your mental health through your gut. Make sure that you start by including more fibre in your diet. You should aim to eat 30 grams per day. Weigh your options on C-Sections and whether you jump into an antibiotic or antidepressant use. Thank you, Ted, for all of the helpful information and if you found this interesting please share it with a friend that would enjoy as well!
Author: Kriben Govender
Food Scientist and Founder of Nourishme Organics
Linked In: https://www.linkedin.com/in/kribengovender/