Professor John Cryan, University College Cork
Apart from aiding digestion, and keeping bad bugs at bay, evidence is also emerging that our intestinal microbes can also affect our behaviour and even the way the brain develops. Neuroscientist John Cryan is exploring this at University College Cork, in Ireland, and he outlined the most recent research to Chris Smith...
John - The whole concept that your gut signals to your brain might not be so new because we use it in our language like gut feelings and gut instincts. The actual pathways of this is only been slowly figured out right now and among those that we’ve been working on is now. In particular, there's a nerve called the vagus nerve which is very important for sending signals from the periphery to the brain. And we’ve shown that that's important at least for some of the effects of bacteria. We know bacteria can produce a variety of neurochemicals that can affect different aspects of physiology. Some of these chemicals that the bacteria produce if they get into the bloodstream can get to the brain and can actually influence brain function. This is another area we’re working on.
Chris - So, what evidence have you got that this may genuinely be happening?
John - Most of the evidence to-date comes from studies in mice and rats, and I suppose what we got into in the first place was the fact that we found that if stress had a long term affect on the signature of these bacteria in the gut.
Also, we’ve shown and others have shown, if you take away bacteria and create a germ-free environment in animals, you have a very increased stress response. So therefore, having a normal stress response is dependent to having appropriate bacteria in your gut. So therefore, we ask to flip question which is really, could we modulate the stress response by targeting the bacteria within your gut?
And so we did some studies where we fed some adult mice with the specific bacteria and we found that these mice were a lot more chilled out, relaxed, and did have the same stress response. And so, when we looked at whether the vagus was involved, we show that these are all dependent on the signal to this neuronal pathway, the vagus nerve.
Chris - So, your theory might be then that the bacteria in some way adjusts the biochemistry of the gut where they are and this is picked up by the vagus nerve and relayed to the brain where that in turn alters what the brain is doing?
John - Absolutely!
Chris - So, what might be the implications then of someone taking a hefty course of antibiotics and these clearing out? Many of the healthy or so-called good bacteria that live in the gut, might that have a mood altering effect?
John - Good studies on this haven't been really carried out to be honest. That said, we’ve shown, and others, that the impact of antibiotics in early life can have widespread effects on physiology later in life.
We’ve shown that there's like an increased visceral pain, abdominal pain in animals that have been exposed to antibiotics early in life. So, the studies, if you need to take antibiotics in adulthood, really, there's nothing robust to indicate that there is a bad effect on brain and behaviour. But perhaps during more neurodevelopmentally sensitive time periods that this is going to be more robust.
Chris - Do you think then we might be able to extrapolate this to other things like breastfeeding or caesarean section? Both of which had been linked to a shift in the kinds of bugs that colonise the gut and that change in gut colonisation seems to persist into adulthood? So, experiments have been done on animals that are breastfed, or not breastfed, and they end up as adults with quite a different type of bacterial spectrum living in their intestines, same with caesarean section. Do you think there might be some repercussions from that then?
John - Absolutely! I think this is really exciting area that has gone ignored up to now. We know that especially early in life, some of the factors that as you mentioned, the mode of delivery and mode of nutrition provision are two of the biggest ways that we manipulate the gut microbiome. and so, people are beginning to look at this and try and do this mechanistically.
Indeed, we have some preliminary data to show that there are long term effects of being born. At least in animals, are being born by C-section and compared to being born by normally delivery. And the literature isn’t that clear.
We know in the C-section born babies, there's an increase in asthma and allergy and maybe other autoimmune diseases. But the link with neurodevelopmental disorders isn’t that clear as a yes, but it deserves more study and it’s something that we’re doing a lot of investigation on right now with C-section rates escalating especially elective C-section in the developing world, something we need to take a lot of caution and investigate thoroughly.
Chris - What about the question of autism? Is there any association possibly with what's going on in the intestine and autism?
John - What we found actually in our studies in mice that lacked bacteria, these are what we call germ free cells. They're the equivalent of a mouse in a bubble, like a boy in the bubble.
These animals when they grow up, we find lots of different changes in their brains and on their behaviour. These changes tend to be much more prevalent in males than females.
That's surprising. And so, that kind of thinking, well autism for example is a disorder which is 4 times more prevalent in males than females. And so, we started exploring social behaviour which is one of the key symptoms of autism and these mice with lack bacteria have clear, social deficits. So, to have normal social behaviour, we need to have normal levels of bacteria in our gut. That much is clear and then really interesting work form Caltech. They showed them in a mouse model of autism that there is differences in gut microbiota, differences in the leaky gut, and that they could reverse these really dramatically and the behaviour by giving a specific bacteria just after weaning. And so, this opens up the concept at least that there could be in the future, potentially for the development of bacterial interventions for autism.