David Perlmutter: There are some absolutely avant-garde researchers who have finally made a huge leap and have decided to look for brain answers outside of the brain, and that seems somewhat counterintuitive. I mean, they once asked Slick Willie Sutton the bank robber, 'Why do you rob banks?' And he said, 'Well, that's because that's where the money is.' And similarly, brain research in terms of diseases has been focused on the brain all of these years, and really has come up pretty empty-handed when you think about the fact that we have no meaningful treatment for Alzheimer's, autism, Parkinson's and MS. And the really exciting news for me as a brain specialist is the fact that we are now uncovering powerful information in the gut that strongly relates to the health and viability of the brain.

Lynne Malcolm: According to influential neurologist from the US, Dr David Perlmutter, there is some good news about the treatment of brain disorders in the future. Cutting edge science is discovering that to an extraordinary degree, not only physical health, but brain and mental health is dictated by what goes on in the gut.

First, here's Boston based psychiatrist Dr James Greenblatt on the workings of our gastrointestinal tract, and the role of its bacteria.

James Greenblatt: The microbiome is the collection of bacteria in the GI tract, and for years we always thought that our thoughts and our feelings affect our GI tract, so we might get stomach aches, we might get diarrhoea when we are nervous. But over the past 20 years or so we now understand that the gut can affect brain function. The amount of bacteria that we harbour in our GI tract is massive. There are more cells, more bacterial cells in our gut than there is in our entire body, three to four pounds of total weight of bacteria, and what we are finding is that this collection of bacteria, this microbiome if you will, has tremendous neurophysiological effects on mood and behaviour and appetite.

Lynne Malcolm: We'll hear later how James Greenblatt at Walden Behavioural Care in Boston uses information about his patients' gut function to treat brain-based conditions.

But this idea goes back 2,000 years. It was renowned Greek physician Hippocrates who said that 'all disease begins in the gut'. Today we take a closer look at how scientists are starting to see the gut as our second brain.

David Perlmutter is author of the New York Times bestselling book Brain Maker. He believes there's a medical revolution underway with the potential to treat a range of brain related disorders, including autism, ADHD, MS and Alzheimer's disease.

Up until a couple of centuries ago, the brain and the body were considered an integrated whole, but with the more recent trend towards reductionism, the brain and the gut have been seen as quite distinct.

This separation is absurd according to David Perlmutter, who joins me now via Skype from the US. He says so many issues related to the gut are profoundly influential in the brain.

David Perlmutter: We know that the gut, for example, makes more than 90% of very important neurotransmitters, like the happy chemical serotonin that is the reason people take antidepressants, to raise that chemical. More than 90% of that is made in the gut. The gut plays a huge role in detoxifying the body, keeping the brain in a healthy state. The gut manufactures various vitamins that are critically important for the brain.

And really exciting is the understanding that the gut and specifically the bacteria that live within the gut regulate the process of inflammation in the human body. And make no mistake about it, inflammation is the cornerstone of virtually every degenerative condition throughout the body, not just the brain. Inflammation is what is thought to be operative in Alzheimer's, Parkinson's, autism, coronary artery disease, diabetes, and even cancer. So when we understand that inflammation is regulated by the gut, and specifically by the level of good versus bad bacteria that live within the gut, then we suddenly realise that we have got a powerful new area to explore that can finally give us new leverage points in dealing with our most pernicious maladies.

Lynne Malcolm: You mentioned serotonin, and a large proportion of serotonin that we produce is produced in the gut, and how that relates to depression and the use of antidepressants. Can you just explain that mechanism?

David Perlmutter: Certainly. So most of the common antidepressants that are used today are called SSRI, and that stands for selective serotonin reuptake inhibitor. It means that basically when serotonin is in the space between two nerve cells, it is taken in in that junction and is less able to be active. When you take one of these drugs, it inhibits the uptake of serotonin, so it's around longer and basically more active. You are in a sense trying to increase the level of serotonin in the brain.

But the notion that serotonin is only in the brain and only works in the brain is now recognised as being extremely myopic. We understand that most of the serotonin in the body isn't in the brain, it's made in the gut. So when we see changes in the gut bacteria resulting in inflammation, driving down available serotonin, it gives us a strong connection in terms of our understanding as to why depression is now looked upon as representing an inflammatory disease. It's the same process occurring in the brain that underlies depression and autism and even Alzheimer's disease. And now we know that the set point of inflammation in the human body is dictated by the balance or the lack of balance of the bacteria that live within us.

Lynne Malcolm: What connects the gut and the inflammation in the gut to the brain?

David Perlmutter: It is directly connected through a nerve called the vagus nerve. The gut itself, often called the second brain, is richly, richly innervated with nerves throughout its extent in what is called the enteric nervous system, and these two systems communicate instantaneously via electrical cables. So the brain is physically connected to the gut, and it is chemically connected to the gut.

There are many pathways by which this happens. One of the most studied is the action of a chemical that lives in the gut, it's called LPS, it stands for lipopolysaccharide. When it gets through the gut wall, when the gut wall isn't functioning appropriately, in other words when the bacteria are imbalanced or when we've consumed certain foods that challenge the gut lining or take certain medications that challenge the gut lining, then this LPS gets out and stimulates certain white blood cells that then go on to create the chemical mediators of inflammation called cytokines. So this is a process by which changes in the gut through this chemical LPS get out of the gut into the systemic circulation and amp up inflammation.

Now, you can measure LPS very simply, we do it with our patients. So we see published peer-reviewed research that show high levels of LPS in Alzheimer's disease, major depressive disorder, autism. So we are beginning to see evidence now that these brain related disorders have something related to the gut that is amping up inflammation. So it's time to look elsewhere in terms of outside of the brain for answers to these very, very challenging problems that I deal with every day.

We've seen what are called interventional studies dating back as much as a decade ago that have shown changes in mood when human subjects have been given specific strains of probiotic bacteria. And I think that ultimately what we can expect would be research that is going to translate into some treatments for depression and anxiety that are not necessarily pharmaceutical, that are more based upon manipulating the microbiome, a far safer way of realising significant changes in physiology, as opposed to treating problems so far down the line, like giving those antidepressants that finally work once the serotonin is in the brain. These new therapies that this research is looking at are looking at finally the fire, not just the smoke.

Lynne Malcolm: Could you briefly outline what puts the balance of the bacteria out in the gut?

David Perlmutter: Excellent question. And to take a step back, we realise that when we compare the gut bacteria in rural populations, in non-industrialised places, there is a much richer diversity of bacteria that live there, and various ratios of the bacteria that we don't see in Western cultures. When you live a cosmopolitan lifestyle, this significantly changes both the array of the bacteria that live within us, as well is the diversity of these very, very important organisms.

And many factors are involved. On the top of the list, the common diet of Western cultures being very high in carbohydrates, in simple sugars, very low in fibre, and also having the wrong kinds, for example, of fats. The other big issue is of course medication. Antibiotic usage has a huge role to play in damaging the gut bacteria, and new reports are indicating that this damage that occurs is permanent. And certainly in Western cultures we are dramatically over-using antibiotics for every cold and sniffle.

75% of the antibiotics that are used here in America are actually used in creating livestock, to make cattle fatter, to make chickens grow more quickly and eggs et cetera, and then we consume those foods. So we are just beginning to understand that Western cultures' microbiome is dramatically different from more rural agrarian populations. The only variable here is the modern cosmopolitan lifestyle, and it may well be responsible for the incredible explosion of these degenerative conditions that we are seeing so prevalent in our modern world.

Lynne Malcolm: David Perlmutter.

Dr James Greenblatt also notes a recent change in our understanding of bacteria in our bodies.

James Greenblatt: More and more research about the vast number of bacteria throughout our body, on our skin, in every aspect of human physiology, most concentrated in the gut, helped our scientists begin to do research looking at the connection between increases in autoimmune disorders, allergies, asthma, and a whole host of disorders that we now trace back to what we are calling an overly clean environment, erasing all the microbes, and the concept of bacteria being evil villains that we have to wipe out with antibiotics. We are now seeing the backlash that these microbes…we have this symbiotic relationship and they provide critical function in both the GI tract and throughout our bodies.

Lynne Malcolm: James Greenblatt. He's one of a small number of psychiatrists who are taking into account the state of his patients' GI tract when treating them for brain and behavioural conditions.

And David Perlmutter in his book Brain Maker discusses the link between the gut and ADHD in children.

David Perlmutter: This whole notion of ADHD is relatively new. The connection of, for example, ADHD to the gut dates back to some really very interesting research that shows significantly higher levels of ADHD in children who were born by caesarean section. And what these researchers did was basically compared risk of developing ADHD with method of birth, and they found a threefold increased risk of developing ADHD if in fact a child was born by caesarean section.

How this relates to our discussion today is that the process of being born is a very important event in the development of a child's microbiome because as you pass through the birth canal the child picks up all kinds of bacteria from the mother. These bacteria go in through the nose and the mouth and colonise the intestines with exactly the right bacteria that that child will need to develop his or her immune system, to break down milk and food that it then eats. And when we deprive children of that, it sets the stage for some very important issues. There is a significant increased risk of ADHD, as mentioned, of autism, of type I autoimmune diabetes, coeliac disease, allergies, and even becoming obese as an adult when a child is born in that way.

So anything that will affect the microbiome, even beginning at birth, I think should be considered in that it paves the way for us to consider that there is a relationship of things gut related to that issue called ADHD.

We've seen some early reports coming in relating the use of probiotics in the actual treatment of ADHD. So this is very exciting research that is now being developed where nutritional modulation is having a role to play in what is thought to be, at least here in America, a disorder that is fundamentally something that we want to treat with drugs.

Lynne Malcolm: David Perlmutter. You'll find details of the research article he mentioned on the All in the Mind website. But it's important to note that birth by caesarean section was shown to be a modest risk factor for the development of ADHD, not the only one. Further research is needed to establish stronger links.

You're listening to All in the Mind on RN, Radio Australia, online and on your ABC radio mobile app. I'm Lynne Malcolm. We're discussing the link between our brain and the balance of bacteria in our gut. Could this area of science offer new treatments for a range of brain and mood conditions?

James Greenblatt is a Boston based psychiatrist who believes that some mental issues can be solved by targeting the digestive system. He's CMO of Walden Behavioural Care and author of numerous books including From Bowels to Behaviour: How Gut Bacteria Influences Neurochemistry.

James Greenblatt: What we're finding is children that have taken numerous antibiotics for it could be ear infections are the most common, it disrupts the gut flora, it kills the offending pathogen as well some of the healthy bacteria in the gut, and it sets up an imbalance. In the field it's called a dysbiosis. So we have overgrowth of a yeast called candida, a certain strain of yeast, and we have overgrowth of other bacteria that can produce toxic metabolites that have direct effects on brain function.

Lynne Malcolm: So how did you come to take this into account in your practice?

James Greenblatt: 20 years ago we were looking at this dysbiosis in primarily autistic children, they have disturbed GI function, many chronic gastrointestinal problems, and we looked for bacterial metabolites of clostridia, it's a metabolite that's shorthand labelled HPHPA. And with autistic kids, there was a large number that we were seeing that had these metabolites, and if we aggressively treated this clostridia metabolite we saw improvement in brain function. The metabolite actually disrupts dopamine metabolism in the brain, so it inhibits the breakdown of dopamine, which means we have kids that are agitated, sometimes aggressive.

Lynne Malcolm: In James Greenblatt's practice they take a holistic integrative approach. As he said, they found a link between the balance of gut bacteria and autism in children. Then they began to see an association between gut bacteria and other psychiatric conditions. He describes the case of one of his teenage patients, Mary, who came to him with obsessive compulsive disorder.

James Greenblatt: We did a test called an organic acid, which is how we pick up this elevation of this chemical HPHPA, so it's a urine test. And the clostridia in the gut that's overgrowth produce high amounts of this chemical called HPHPA, so when we detected this and with Mary in her presentation to the office with very severe OCD, she was incapacitated by her obsessive thoughts and her rituals, unable to get to school and function. She had tried multiple medications, went to clinics around the US to treat her OCD, but it was until we addressed her GI tract with very high doses of what's called probiotics, good bacteria, were are we able to gradually see this improvement in her disabling obsessive compulsive disorder.

Lynne Malcolm: So tell me about the probiotics. What are they and how do they work?

James Greenblatt: Probiotics are various strains, and there are thousands of bacteria that inhabit our GI tract. The research is young, so it's very hard to know which strains do what. I think the reality is the research is not quite able to pinpoint that this bacteria is good for depression or anxiety or weight loss, but it's clear that there are a couple of things the research has repeatedly shown. The diversity of the microflora in the gut is healthy, and we are able to introduce probiotics, healthy bacteria, into the gut to make a difference in both GI tract function and behaviour. So probiotics would be the nutritional supplement based on the strains of bacteria that has been cultured and grown that are introduced into the body and they can be obtained at a health food store or through physicians' offices.

Lynne Malcolm: James Greenblatt is unusual, being a psychiatrist who treats the gut for mental health issues, but he says that the scepticism in his field is decreasing. So, to what extent does he believe that changing a person's microbiome can be effective in treating brain conditions?

James Greenblatt: In all the work that I do and the books that we've been writing over the years, it's really based on the concept of what we call biochemical individuality. So giving probiotics to everybody who is depressed or who has obsessive compulsive disorder is not going to be the answer. We are all looking for that silver bullet. But by looking at individual testing, there's a percentage of individuals with major psychiatric illness, from autism, schizophrenia, depression…we had one case of long standing trichotillomania, hair pulling, that completely reversed with these high dose probiotics. So by looking at some of these urine tests and these stool tests to be able to predict which individuals have this imbalance, then we have a high success rate of using probiotics.

I think the research has been quite varied and I think it's in its infancy. And the clinical applications have not really been settled and that's why there's still controversy in the field, and the research is in its infancy. A group of us who have been looking at this for over 20 years have been able to make those clinical correlations between these abnormal lab tests and selecting probiotics.

Lynne Malcolm: So what cautions do you think that we need to take in this field in order not to overstate the potential of treatment via the gut brain connection?

James Greenblatt: I think the things that are quite clear is diversity of the microbiome is healthy, and there are a few markers that we do have is that we can look at. My caution and concern are some of the nutritional supplement companies based on one small study that they have this probiotic that's going to treat depression, another probiotic that's going to treat obesity, another probiotic that's going to regulate cravings. I think that's where the caution needs to be heeded as more and more research needs to be looked at.

I think the simple implication here is that we need to take care of our gut and eating healthy fermented foods that provide this ongoing introduction of healthy bacteria is critical. Most major cultures in the world have always had fermented foods. And taking probiotics is critically important for our overall health. And for those individuals struggling with mental illness, looking to see if some of these overgrowth of clostridia or yeast are in fact a factor can be tremendously helpful.

Lynne Malcolm: Dr James Greenblatt.

David Perlmutter is very optimistic about the potential of probiotics in the treatment of brain conditions.

David Perlmutter: We're just beginning to see studies appearing that show that early life probiotic supplementation during the first six months of life has been shown to significantly reduce the risk of developing ADHD or what's called Asperger's syndrome (which is something on the autistic spectrum) dramatically. And this was a study published in the journal Paediatric Research. I actually have it on my website, I wrote a blog about it. So it's early, and I think you are probably looking for more robust research and it isn't quite there yet, but it is happening and it's pretty darn exciting.

Lynne Malcolm: So do you think that you are at risk of overstating the brain-gut connection and the effectiveness of probiotics and supplements as treatment? Because many of the disorders and conditions you talk about are very serious, and if the treatment is ineffective or inappropriate it can have significant impact on people's lives.

David Perlmutter: I don't think I'm overstating. There is not a robust level of research indicating the effectiveness of, for example, probiotics. But I think the exciting part for me as a clinician, as an individual dealing with patients all the time, and that is that I think the door is open to a whole new area that we never conceptualised before. Now I think I can at least say that I for one as a brain specialist am very hopeful that there are new opportunities to treat patients, but I think that it needs to be done in a very measured, careful, safe way. We always want to operate under the dictum of 'above all, do no harm'. So I think your point is very well taken.

Lynne Malcolm: There has also been some criticism that there are products…and I think you are involved in some of the companies that produce the probiotics and the supplements you prescribe…is there a conflict of interest there?

David Perlmutter: Clearly there could be. There is a company that I'm working for here in America that I'm helping, I'm serving on their scientific board, creating these products based upon peer-reviewed science. So could there be a perceived conflict of interest? Absolutely there could be. People will perceive whatever they want. But I have never prescribed any of these specific products to a patient.

Lynne Malcolm: What do you think the most important next step in gut-brain research is?

David Perlmutter: Some of the most influential thought leaders on the planet are getting together to be involved in studying the microbiome with an emphasis on actually treating disease. We are just beginning to see our researchers have the ability to use the techniques of characterising the gut bacteria, but to analyse this data with some incredibly powerful computer systems, to crunch this data, to first determine what is a healthy microbiome, and then to correlate specific changes in the gut bacteria and the metabolites of these altered gut bacteria. In other words, what they are manufacturing or not, and determine how this data carries over to health and disease. Then we can begin to undercover and develop ideas in terms of making the gut bacteria more normal in hopes of treating these diseases. But again, we've got a way to go until we are able to really get our arms around that as a concept.

Lynne Malcolm: Dr David Perlmutter, author of Brain Maker. More details can be found on the All in the Mind website, find your way there via the RN home page.

Production today is by Muditha Dias with sound engineer Judy Rapley.

I'm Lynne Malcolm. Great to have your company. Catch you next time. Bye for now.