Gut bacteria steer the development of the young brain

By Ed Yong | January 31, 2011 3:00 pm

This isn’t something a mother wants to hear: when you gave birth to your child, you laced it with millions of unseen forces that are shaping the way it thinks and behaves. Under their influence, your baby’s nerves will grow and connect in ways that will affect everything from how anxious to how coordinated it is. Thanks to your very first birthday present, your infant’s brain is being shaped by its gut. Or, more accurately, what’s inside its gut.

The bowels of every baby are filled with trillions of bacteria that outnumber the cells of our own body by ten to one. This “microbiome” acts like on of our own organs, harvesting energy from our food and blocking the growth of harmful bacteria. It’s also a gift from our mothers. In the womb, we’re largely sterile. It’s only when we pass through the vagina that we’re seeded with our first set of bacteria. This community of passengers changes as we grow up, shifting in membership as we move from milk to solid food.

But the bacterial passengers of HMS Baby don’t just react as their vehicle develops; they help to steer it too. By studying mice, Rochellys Diaz Heijtz from the Karolinska Institute has found that a mammal’s gut bacteria can affect the way its brain develops as it grows up. They could even influence how it behaves as an adult.

Heijtz worked with two strains of mice – one that was completely free of germs, and another that had an intact microbiome but no disease-causing bacteria. The two strains behaved differently. The germ-free mice were more active, and spent more time scurrying around their enclosures. They were also less anxious and more likely to take risks, such as spending long periods of time in bright light or open spaces.

Could it really be that gut bacteria were behind these differences? Heijtz proved as much by transplanting the microbiome of the disease-free mice into the bowels of the germ-free ones. Sure enough, when the inoculated babies grew up, they behaved in the “normal” cautious way, just like the disease-free ones. This only worked if Hejitz did the transplants on baby mice. If she gave sterile adults a shot of gut bacteria, their behaviour didn’t change.

These differences aren’t just skin-deep. The absence of the gut bacteria also triggered a slew of changes in the rodents’ brains. Heijtz compared her germ-free and disease-free mice and found that over a hundred genes were twice as active in the brains of one strain compared to the other. Some of these genes are involved in providing cells with energy, others in chemical communications across the brain, and yet others in strengthening the connections between nerve cells.

How do these bacteria, lurking within the bowels, affect the fate of the brain, half a body away? For a start, they have a direct phone – the vagus nerve. This long branching nerve transmits information about what happens in the gut (and other organs) to the brain. But the bacteria could also route their calls via hormones. By definition, these are chemicals that can affect parts of the body over long distances. By changing hormone levels, the microbiome can ensure that what happens in the gut doesn’t stay in the gut.

For example, a Japanese team found that gut bacteria can change levels of stress hormones in the body. And an American group found that germ-free mice have almost three times more serotonin in their blood than normal ones. Heijtz herself found that chemicals like noradernaline and dopamine came and went at a faster pace in her germ-free mice. All of these chemicals could affect the way the young brain develops.

Heijtz’s mice tell us that there’s an important window in early life when the microbiome can affect the way its host develops. And this could very well depend on the bacteria that you start with. For example, babies end up with a less diverse set of skin and gut bacteria if they are delivered through Caesarean section than through the vagina. This could affect how susceptible they are to diseases. If Heijtz’s work in mice applies to humans too (and other microbiome studies have found comparable results between the two species), the way a child is born could affect its brain and behaviour.

Hejitz’s work is part of a rapidly growing number of studies, which show the wide-ranging influence of our hitch-hiking trillions. She joins Gil Sharon from Tel Aviv University, who found that the bacteria can change the sexual preferences of fruit flies. And other scientists have put forward specific species of gut bacteria as potential culprits in the development of autism.

These passengers do much more than process our food, and we are much more than just their containers. They’re part of us and our evolutionary history (you can even recap the evolution of apes by looking at the bacteria in our guts). We’re each like a superorganism – a unified alliance between the genes of several different species, only one of which is human.

Reference: Heijtz, Wang, Anuar, Qian, Björkholm, Samuelsson, Hibberd, Forssberg & Petterson. 2011. Normal gut microbiota modulates brain development and behaviour. PNAS

Images by Shushruth and Rama

More on the microbiome:

An introduction to the microbiome

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