Tuesday, November 4, 2014

'Healthy' microbes not always good

Nov 03, 2014


IN THE late 17th century, Dutch naturalist Anton van Leeuwenhoek looked at his own dental plaque through a microscope and saw a world of tiny cells. He could not have predicted that a few centuries later, the trillions of microbes that share our lives - collectively known as the microbiome - would rank among the hottest areas of biology.

These microscopic partners help us by digesting our food, training our immune systems and crowding out other harmful microbes that could cause disease. In return, everything - from the food we eat to the medicine we take - can shape our microbial communities, with important implications for our health. Studies have found that changes in our microbiome accompany medical problems from obesity to diabetes and colon cancer.

As these correlations have unfurled, so has the hope that we might fix these ailments by shunting our bugs towards healthier states. The gigantic probiotics industry certainly wants you to think that, although there is little evidence that swallowing a few billion yogurt-borne bacteria has more than a small impact on the trillions in our guts.

The booming genre of microbiome-diet books peddles a similar line, even though our knowledge of microbe-manipulating menus is still in its infancy.

This quest for a healthy microbiome has led some people to take measures that are far more extreme than simply spooning up yogurt.

In September, archaeology writer Jeff Leach used a turkey baster to infuse his guts with the faeces of a Hadza tribesman from Tanzania.

Doctors have carried out hundreds of faecal transplants, particularly to treat people with unshakeable infections of the diarrhoea-causing bacterium Clostridium difficile. The procedure has been spectacularly successful, far more than conventional antibiotics.

But Mr Leach did not have C. difficile. He experimented on himself because he views the Western microbiome as "a hot microbial mess", he wrote on his blog. Poor diet, antibiotics and overly sanitised environments have gentrified the Western gut, he wrote, "potentially dragging us closer to ill health".

The Hadza, with their traditional hunter-gatherer lifestyle, carry diverse microbial communities that are presumably closer to a healthier and disappearing ideal. Hence, the stunt with the turkey baster. Mr Leach billed it as "(re)becoming human".

This reasoning is faulty. It romanticises our relationships with our microbes, painting them as happy partnerships that were better off in the good old days. It also invokes an increasingly common trope: That there is a "normal" or "healthy" microbiome that one should aim for.

There is not. The microbiome is complex, varied, ever-changing and context-dependent - qualities that are the enemies of easy categorisation.

"Healthy" microbes can easily turn rogue. Those in our gut are undoubtedly helpful, but if they cross the lining of the intestine and enter our bloodstream, they can trigger a debilitating immune response. The same microbes can be beneficial allies or dangerous threats, all for the difference of a few millimetres.

Conversely, "unhealthy" configurations of microbes can be normal, even necessary. Ruth Ley at Cornell University and colleagues demonstrated this when they found that microbiomes go through a huge upheaval by the third trimester of pregnancy.

The microbiomes end up looking like those of people with metabolic syndrome - a disorder that involves obesity, high blood sugar and a higher risk of diabetes and heart disease. Packing fat and building up blood sugar make sense when you are nourishing a growing foetus.

The dynamic nature of the microbiome partly explains the enthusiasm that surrounds it. If scientists identify changes in the human genome that increase the risk of disease, it is hard to rewrite those genes or to find drugs that target them.

But the microbiome could theoretically be altered through probiotics, faecal transplants or other means.

How can you tell when it needs replacing? A bloom of C. difficile is an obvious problem, but most other communities are not classified so easily.

We need to start thinking about it as an ecosystem, like a rainforest or grassland, with all the complexities that entails.

Take the Hadza. Their microbial roll call is longer than a Western one, with both omissions and additions.

They are the only adult humans thus far sequenced who are devoid of Bifidobacteria - a supposedly "healthy" group that accounts for up to 10 per cent of the microbes in Western guts. But they do carry unexpectedly high levels of Treponema, a group that includes the cause of syphilis.

Is this menagerie worse than a Western one? Better? I suspect the answer is neither. It is simply theirs.

It is adapted to the food they eat, the dirt they walk upon, the parasites that plague them. Our lifestyles are very different, and our microbes have probably adapted accordingly.

It may be that a Hadza microbiome would work equally well in an American gut, but incompatibilities are also possible.

The microbiome is the sum of our experiences throughout our lives: the genes we inherited, the drugs we took, the food we ate, the hands we shook. It is unlikely to yield one-size-fits-all solutions to modern maladies.

We need to learn how tweaking our diets, lifestyles and environments can nudge and shape the ecosystems in our bodies. And we need ways of monitoring a person's microbiome regularly to understand how its members flicker over time, and whether certain communities are more steadfast than others.

Our microbes are truly part of us, and just as we are vast in our variety, so, too, are they. We must embrace this complexity if we hope to benefit from it.


Mr Yong is a freelance science writer.

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