Paper trail
Artist’s loo paper submitted to the medical journals.
Toilet paper used by artist Billy Apple nearly 50 years ago has given Liggins Institute researchers new insights into how the gut microbiome changes over time. The toilet paper was part of an Apple exhibition at the Serpentine Gallery in London in 1970, although it was quickly shut down as a potential health risk.
Last year, after Apple heard of the microbiome research, he offered up the three samples he’d taken during toilet stops on three successive days – along with three new samples, also taken on consecutive days.
Scientists were then able to genetically identify the bacteria in each of the samples and establish how they’d changed.
Molecular microbiologist Justin O’Sullivan says the comparisons showed that although the samples taken on successive days were very stable, only 45% of the original bacteria types remained decades later.
Certain genetic variants correlate with the presence or absence of particular species of gut bacteria. Because Apple has had his genome sequenced, the researchers were able to show that he had some types of bacteria but not others as a result of his genes.
O’Sullivan says the survival of nearly half the gut flora suggests that a selection process is at play, “otherwise, why would you keep it?”
“Instead of the microbiome simply being imposed on you, you select for some components of it, saying, ‘I need this bacterium but I don’t need that one.’”
Apple is listed as a co-author on a paper being submitted to medical journals, entitled, “The faecal microbiome of Billy Apple® 46 years apart.”
Says O’Sullivan: “Supplies of 46-year-old poo along with medical histories that are well documented and linked with that individual are non-existent.”
by American gastroenterologist Robynne Chutkan (see box page 19), that claim to show how a change in diet can improve the microbiome.
“Really radical changes in diet will produce changes in the microbiota,” says Tannock, “but most of us are not [making them]. A lot of data shows that, for an individual, we have pretty much the same microbiota over long periods of time. Our impression is it’s a stable community and that fits well with ecological theory in general that microbial communities in nature are self-regulating and remarkably stable.”
He disagrees with Cutfield, who estimates that about 30-40% of the microbiome is stable, with the rest changing in response to lifestyle, diet and use of antibiotics and alcohol. “If you have a bad weekend and drink lots of alcohol, you’re going to really disrupt your gut microbiome. It recovers, but how quickly is still not clear.”
Work led by Justin O’Sullivan that has looked at Billy Apple’s microbiome (see box page 20) supports the idea that the microbiome changes over your lifetime, but that some of it is conserved.
Tannock says the differing opinions reflect the fact that our knowledge about the microbiome is far from perfect. And, he says, it’s more complex than just counting the types of bacteria present. Bacterial cells can switch their biochemical pathways, depending on the type of food they’re required to process.
“When they are presented with indigestible food A, they have a particular metabolism, but the next day, if they are presented with a different [molecule], they switch to a different pathway.”
Just because different people have a proportion of their microbiome made up of different species of bacteria doesn’t mean it’s going to work differently, Tannock says.
“In the bacterial world, there is a huge degree of redundancy, so different kinds of bacteria can carry out the same function.”
Much has been made of the number of bacteria in our gut and the significance of their potential impact on our health. A widely quoted, but incorrect, figure from 1972 suggested microbes outnumbered human cells 10 to 1. More recent estimates suggest the ratio is about 1:1, says cell biologist Professor Mike Berridge of the Malaghan Institute in Wellington. “We all have about 30-40 trillion microbes, 95% of them in our gut, and roughly the same number of cells in the body. The important thing is we need to recognise this and come to grips with the fact that as humans, we need to understand how to work with them, and that human diseases are very much related to our interface with our microbial population.”
CAUSE OR EFFECT?
It’s a lot more complicated than the chicken-and-egg scenario: does the makeup of the microbiome we inherit and develop as children predispose us to particular health outcomes, or do our lifestyle choices alter our microbiome in problematic ways? The answer is probably a bit of both.
“Bacteria and products from bacteria are talking to the immune system all the time,” Berridge says. “You might have a gene that predisposes you to obesity, but you can influence the way that gene or set of genes plays out by lifestyle choices. If you try to get the best diet you can, you’re going to end up with the best microbiome you can have.”
Berridge is particularly interested in the links between the quality of the diet and, in particular, how sugar affects obesity. “Sugars are produced in the digestive processes that the microbiome contributes to, and it’s going to be tweaking and modifying those.”
Some researchers believe the microbiome plays a very big role in weight control, but Berridge estimates it may be only a 10-20% contributor.
So, could poo pills inoculate us against our typically crappy diet? “Good question,” says Cutfield. “We’re hedonists; we eat too much and we don’t exercise enough. But we’ll untangle that from the study.” If the experiment works, he says, it’s potentially a sustainable treatment and should eventually be able to be produced relatively easily and cheaply in the lab with cultured bacteria. Most importantly, he says, based on clinical trials of GMT in other conditions, “we know it’s safe”.
The microbiome does not replace or contradict other longunderstood causes of obesity; it is thoroughly entangled with them.