Interview by Christopher Sumpton

How do you describe what’s been called the microbiome in the gastrointestinal tract?

If you take the microbiome in the GI tract, from your lips to the anus, you have a lot of different microbial species. You can take just the bacteria. We started some decades ago and thought it was maybe 30 to 40.  So, it was two or three years ago the number of species reached 1,000.  Now, we are talking about at least 2,000 species are colonizing you, are living together with you.  And the number may vary in the different tract.  In your mouth, you have at least 800 different microbial species.  You may have a small mouth or you may have a big mouth, but you have a high number of different species anyhow.  In your GI tract, in your stomach, you have microbes there, and in the small intestine you have an increasing number of microbes all the way down in your small intestine. And in your colon, you have the highest number.  So altogether, you have at least 2,000 different species.  And if we are then talking about strains, you have even more.  And each of the species are maybe quite different from each other. And so, you see, all these microbes, they have genes, so they—and genes mean functions, so that means that you do have a functional system within yourself. It’s a little bit discussion how many functional genes a human being have.  Maybe, if you say 50,000, it can be more, it can be less. And the microbes, if you just take a round number of 4,000 or 5,000, for each of the different species, and if you have 2,000 different species, then you have some millions of genes within your GI tract that can do something, and if they have the opportunity, they will do something with you and what you are eating or what you are taking into your GI tract.

 What are the bacteria that live in our guts doing for us and what do we do for them?

The most important thing about the bacteria is very simple: they want to be there. They want us to stay alive. By being there, they receive food, they received water, they have a very stable milieu all the time, around 70—37 degrees Celsius. Very little oxygen. So, they like to be there. It’s as simple as that. In fact, they are doing a lot for us. If you are taking an example from tests of germ-free and conventional animals, the germ-free animals that need much more artificial nutrients. So, the microbes in our GI tract are not taking the food away for us, they are solving the problem. They are utilizing the fibre you are eating every breakfast. You cannot utilize that fibre yourself. You cannot break it down. The microbes can and by doing that, they are serving us energy. It’s as simple as that. And also, by doing that, they are serving us with peptides, with amino acids, sometimes with vitamins, and so on and so on. So, there’s a lot of good things that happen when you have the right intestinal microbiota.

Can you describe the process by which microbes in the gut can affect the brain?

They are producing a lot of compounds that are very similar to the compounds that we are producing by ourselves. It’s popular now to talk about neurotransmitters and so on, and neurotransmitters are produced by the intestinal flora of course. But it has been known since the 1930s that intestinal flora can produce serotonin and that all the short-chain fatty acids except acetic acid are, in fact, produced by the intestinal flora. They produce acetic acid, proprionic acid, butyric acid, valeric acid, caproic acid, and you name them and they are producing them. And they are absorbed, and as small molecules they will interact at various places in the body.

 Let’s take proprionic acid as an example, could it affect the brain?

That’s the model that MacFabe has established. He started to inject proprionic acid into the brain and then he discovered that in that rat model, proprionic acid act upon the animal and they become more or less autistic. So, it might be proprionic acid, but it might be also other acids. I think he has studied some, but they are not so potent as proprionic acid. It will interact with the metabolism within the brain if it is there. In other studies, if you take another very small acid, if you take an acid that is used to treat epilepsy, valproic acid, that’s also absorbed in the GI tract. It’s going to the brain and interfere with excitatory system in the brain, so an epileptic person will have less attacks. So, it seems to be an acid balance across the cell membrane in the brain. The proprionic acid is an excellent model for studying that in animals. It hasn’t been shown yet that it is the same system that is working in a human being, but as a model it’s good. As an explanation for autism, it’s still a way to go.

 How does the usual balance in gut microbes in a child get to be out of balance?

You are born germ-free. The first week of your life there is unformed chaos in your GI tract. For when you are born, you have increased oxygen tension in your GI tract. You have a high redox potential, so the normal inhabitants can’t live there yet. But from your first week of life, until you are two years old, then more than thousand, close to two thousand species have to be established. So, you are going from sterility when you are born, through chaotic complexity the first week, then to bifidicity the following weeks and months, as long as you are receiving mother’s milk, and then slowly back to the complexity, and with that complexity, you are starting to live together with the microbes. They are living together with you for the rest of your life and each time a new microbe is entering, it has to fit in to what’s there already. You may have windows for establishment; If a particular microbe enters maybe it can be established when you are four months of age. If it’s coming later, it cannot be established. You have a succession in establishment. You can use the bifidobacteria for an example—they cannot be established when you are born. There’s too much oxygen, too high redox potential, so they need the other ones to get rid of the oxygen, to reduce the redox. Then, they can exist there. They depended on microbes A, B, C. Then, they can come. And when they are established, then you have a long-term effect of establishment for each of them can switch on and off genes in your cells and each of them may produce or may not produce some other compounds that will act upon you. So, the key problem you have to keep in mind is windows for establishment, succession in establishment, and long-term effect of establishment. And that may get quite complicated when you are looking at alteration in flora in autistic children, for you don’t know so much about their pre-history. You are looking in at a later period of life. So, it’s still a way to go.

 What about antibiotic treatments during that critical period?

That’s much more profound and much more, let us say, dangerous that we have thought. We did some work on that from a functional point of view. If you gave an antibiotics to an infant… It could be three months old, it could be one year old. Then, the flora become simplified. If it was one year old baby, it looked, from a functional point of view, like it would be six months until a more complex function was established again. And by studying adults, it has been shown that antibiotics take part of the microbes away for more than a year until they can re-establish. It’s like when you leave a crowd, it’s difficult to come in again. You can go to a pop concert: if you are leaving there, you have very difficult to get close to the stage again. It’s the same rules in the GI tract.

 What do you think is the most promising area to focus on for finding treatments for autism?

The most promising area is, in fact, not scientific, but the practical work that you do can do to change the behaviour of the child. You can influence the behaviour. They don’t have to be institutionalized, they can hopefully live more or less together with their family if they are managed properly. I have seen many cases like that. It’s hard work. It’s a lot of details. It’s a lot of breakdowns. It’s a lot of disappointments. But it’s a lot of success as well. It’s especially how you can change the diet, so you are, in fact, interacting with the flora. But the studies so far don’t tell you what is an overgrowth and what is not. They’re just telling something is wrong. And they aren’t telling you that the overgrowth is the cause of autism, it can be that some others are lacking. So, autism can be a shortage of some microbes and not a presence of some microbes, and that’s difficult to investigate, but we have to do it. We have to follow a cohort of children from the very beginning and up, and then you can investigate what’s there and what is not there and what that means.

 What about the work that people like Hanne Bjorg-Walker are doing who are finding successful biomedical treatments?

Yeah, that’s very promising, but that’s much more difficult. It’s far more difficult to treat after early childhood, but she has succeeded by doing step by step and I think there are other people all around that are doing the same. So, they should be encouraged to go further on and they should also be encouraged to share their knowledge with each other. And so, it’s important to have conferences and important to have meetings, but the conferences and meetings should not be run by believers; they should be run by people with an open mind, listening to the different experiences of practical studies. I don’t believe in believers. I believe in people asking questions.

 How hopeful are you about answers being found for the increase in the rate of autism?

You see, I am basically an optimist and if the autism increase is man-made, and so the problem has to be man-solved, and surely, it will be. But it is a challenge from the whole scientific society. It is a challenge for the people working practically with autistic children. It’s a challenge for the government and for all the bureaucrats sitting there. It’s man-made; it should be man solved, and it will. I can take an example from Canada. Before Banting and Best, there was no hope for a diabetic, type 1. So, insulin came and it switched the life for millions of people, very, very abruptly. I don’t think that will be the same in autism. But there are so many studies going on in so many fields, so I’m quite sure that within some few years, it will be a completely different situation.

 Is there a shift going on in the way that medicine is looking at health?

It may be slow but it is a shift. For many years, we looked upon microbes as something that interfere and are bad for our health. Now, we are starting to look upon microbes as a beneficial for our health. We looked upon antibiotics as always good for fighting microbes. Now, we have a broader view on antibiotics. They may disturb as well as acting upon infections. You can see a change in attitude with diet, we are now very, very careful. We are looking how to eat right the right food and so on. In nearly all fields, we are going from a just a therapeutic approach to handle disease to a more prophylactic approach. So then, we have to play together with Mother Nature and our microbiota is part of our nature. It’s part of our self, so we have to cope with the microbiota in order to live a long life in good health. I can see from looking back in my book of internal medicine, it said one sentence about the intestine microbiota. It said my intestinal microbes constitute about 50% of the mass of feces and may be of importance for the consistency of the feces. That was all. Nothing more. And now, people are looking upon the intestinal microbiota as the largest organ in the body: it has the most functions, is the most biochemically active one, the most interfering with immunology. So, the focus has switched, and now the focus is in the GI tract, and I’m very pleased with that. It should have been done decades ago.