Sunday Papers: The Shyer and Spryer Mouse

In this new series, I take a relaxed, science-in-bed-on-a-Sunday look at experiments, ideas, theories or fields of research that just knock me a little bit sideways.

You awaken in a darkened room. To the east, a glimmer of brightness through a doorway. You are a mouse. Do you step into the light?

What you are likely to do in this situation may depend on whose bacteria live in your belly.

Recently, I bumbled across a paper discussing evidence that gut bacteria may influence behaviour, at least in mice. Read those last nine words again. Gut bacteria may influence behaviour, at least in mice. To me, this is a mind-boggling idea. Or a stomach-churning one. Or perhaps both, because the two seem to be deeply linked.

Within your gut live colonies of bacteria and other microbes. And not just in your gut: bacteria, fungi and simple, single-celled creatures called archaea inhabit the nooks and crannies and folds and recesses of your skin, your genitals, your mouth, your eyelids, maybe even your brain.

This is your microbiome. You contain 100 trillion microbes, give or take, and they outnumber human cells by 10 to one. And that’s not counting the viruses. You are mostly not human. You are a zoo.

(100 trillion is a silly number. If you were to count from one to 100 trillion, speaking one number every second, travelling backwards in time, you’d end up over 3 million years in the past. You would be the only Homo sapiens, surrounded by australopithecines, grunting and poking at the weird, hairless creature just landed in their midst gabbling all the silly numbers.)

But, for the time being, you’re not a human; you are a mouse. Do you step into the light?

There are two chambers, one light, one dark. This is the light-dark box. The number of times a mouse steps into the light – and the length of time spent there – signifies mouse anxiety. The more time spent in the light, the less anxious the mouse.

A separate box contains a raised platform. Mice sit on this platform while researchers time how long the critters take to start exploring – another measure of anxiety – by stepping down. This is the step-down test. The prosaic names don’t quite foreshadow the cool things the mice are about to do.

Light Dark box
Step Down test Top: Light Dark box (Source: Mouse Phenome Database)
Bottom: Step-down test (Source: ugo basile)

Into these dystopian contraptions go two types of mice.

The first originates in New York, from the turn of the 20th century. You expect these to be hardboiled, Philip Marlowe mice. Mice living in a whisky-fugged sprawl of dames and guns. But they are anxious and timid. These are albino house mice, exclusively bred in laboratories for over 200 rodent-generations, and – to the inexpert ear – cryptically referred to as BALB/c mice. BALB/c prefers to stay in the dark, to not step down.

The Swiss mice are an altogether more sociable beast. Bred by the National Institutes of Health and not originating from Switzerland (they come from Maryland, USA), these mice are more exploratory, not so shy. They spend more time in the light, less time on the platform.

Researchers from The Farncombe Family Digestive Health Institute at McMaster University in Canada wanted to see what happens when they infused the gut bacteria from mice with one type of personality into the intestines of another.

In an experiment performed in 2011, the team extracted the contents of each mouse’s cecum: the pouch at the beginning of the large intestine. The goo was fed into ‘germ-free’ versions of the two sorts of mice. Germ-free Swiss and BALB/c mice are born without any microbial bugs in their bellies: veritable blank slates.

The sociable Swiss mice were fed the cecal contents from the timorous BALB/c mice, and vice versa. When colonised by their polar opposite’s bacteria, the mice behaved differently. The once-anxious BALB/c mice became more Swiss, stepping down sooner from raised platforms and wandering more frequently into lighted chambers. The Swiss mice, in turn, became more tentative, not so experimental.

Personalities shifted purely based on swapping the intestine’s microbiome. Although they don’t know the exact mechanisms responsible for the behaviour changes, the researchers found that the newly anxious Swiss mice had reduced levels of a chemical called Brain-Derived Neurotropic Factor (BDNF). Some anti-anxiety drugs target BDNF, reducing its levels in the body.

It is too early and we know too little to say exactly what this research means for humans, our behaviours and our health – but it could have implications.

Faecal Microbial Therapy (FMT) is a nice way of describing how infusing bacteria from someone’s poo into an unwell person’s intestines can help make them better. Earlier this year, a clinical trial showed FMT was much more effective than conventional antibiotics at treating severe diarrhoea caused by the Clostridium difficile bacterium. So effective, in fact, that the trial was stopped early because it was unfair to the control group not receiving FMT.

But what does it mean for the future of FMT if shifting gut bacteria can shift behaviour? After talking about the mind-boggling-stomach-churning role of the microbiome, the paper goes on to mention a handful of cases where patients received FMT to treat chronic constipation. These patients also have severe multiple sclerosis (MS), a nervous system condition where the fatty sheathes wrapped around neurons become damaged. After a course of FMT, the three patients experienced what the paper calls ‘neurological improvement’ – remission of some of the symptoms of MS including, in these three cases, regaining the ability to walk.

FMT seems like a promising therapy but beyond anecdotes and smatterings of evidence, we don’t really know just how promising. It’s important not to descend into the hyperbole of televangelist-style miracle cures. A lot more work needs doing. Though perhaps, in a good way, the future will be shit.

Reference: Collins, Kassam and Bercik – 2013. The adoptive transfer of behavioral phenotype via the intestinal microbiota: experimental evidence and clinical implications. Current Opinion in Microbiology