We aren’t single individuals, but colonies of trillions. Our bodies, and our guts in particular, are home to vast swarms of bacteria and other microbes. This “microbiota” helps us to harvest energy from our food by breaking down the complex molecules that our own cells cannot cope with. They build vitamins that we cannot manufacture. They ‘talk to’ our immune system to ensure that it develops correctly, and they prevent invasions from other more harmful microbes. They’re our partners in life.
What happens when we kill them?
Farmers have been doing that experiment in animals for more than 50 years. By feeding low doses of antibiotics to healthy farm animals, they’ve found that they could fatten up their livestock by as much as 15 percent. You can put the antibiotics in their feed or in their water. You can give the drugs to cows, sheep, pigs or chickens. You can try penicillins, or tetracyclines, or many other classes of antibiotics. The effect is the same: more weight.
Consistent though this effect is, no one really understands why it works. The safe bet is that the drugs are exerting their influence by killing off some of the microbiota. Now, Ilseung Cho from the New York University School of Medicine has confirmed that hypothesis. By feeding antibiotics to young mice, he has shown that the drugs drastically change the microscopic communities within their guts, and increase the amount of calories they harvest from food. The result: they became fatter.
We depend on a special organ to digest the food we eat and you won’t find it in any anatomy textbook. It’s the ‘microbiome’ – a set of trillions of bacteria living inside your intestines that outnumber your own cells by ten to one. We depend on them. They wield genes that allow them to break down molecules in our food that we can’t digest ourselves. And we’re starting to realise that this secret society within our bowels has a membership roster that changes depending on what we eat.
These changes take place across both space and time. Different cultures around the world have starkly contrasting diets and their gut bacteria are different too. As we grow older, we eat increasingly diverse foods, from the milk of infancy to the complex menus of adulthood. As our palate changes, so do our gut bacteria.
The Not Exactly Pocket Science experiment continues after the vast majority of people who commented liked the pilot post. I’m really enjoying this, for quite unexpected reasons. It’s forcing me to flex writing muscles that usually don’t get much of a workout. Writing short pieces means being far more economical with language and detail than usual. It means packing in as much information as possible while still keeping things readable. And it means blitz-reading papers and writing quickly without losing any accuracy.
One quick note before the good stuff: last time, a few people suggested that I put each NEPS item in a separate post, but the majority preferred multiple items per post. For now, I’m keeping it that way because otherwise, the longer pieces would be diluted by the smaller ones. We’ll see how that works for the foreseeable future.
Rising DAMPs – when enslaved bacteria turn our bodies against themselves
Our immune systems provide excellent defence against marauding hordes of bacteria, viruses and parasites, using sentinel proteins to detect the telltale molecules of intruders. But these defences can be our downfall if they recognise our own bodies as enemies.
All of our cells contain small energy-supplying structures called mitochondria. They’re descendents of ancient bacteria that were engulfed and domesticated by our ancestor cells. They’ve come a long way but they still retain enough of a bacterial flavour to confuse our immune system, should they break free of their cellular homes. An injury, for example, can set them free. If cells shatter, fragments of mitochondria are released into the bloodstream including their own DNA and amino acids that are typical of bacteria. Qin Zhang showed that trauma patients have far higher levels of such molecules in their blood than unharmed people. Our white blood cells have sentinel proteins that latch onto these molecules and their presence (incorrectly) says that a bacterial invasion is underway.
This discovery solves a medical mystery. People who suffer from severe injuries sometimes undergo a dramatic and potentially fatal reaction called “systemic inflammatory response syndrome” or SIRS, where inflammation courses through the whole body and organs start shutting down. This looks a lot like sepsis, an equally dramatic response to an infection. However, crushing injuries and burns can cause SIRS without any accompanying infections. Now we know why – SIRS is caused by the freed fragments of former bacteria setting off a false alarm in the body. The technical term for these enemies within is “damage-associated molecular patterns” or DAMPs.
More from Heidi Ledford at Nature News
Reference: Nature DOI:10.1038/nature08780
Different gut bacteria lead to mice to overeat
On Wednesday, I wrote about the hidden legions residing up your bum – bacteria and other microbes, living in their millions and outnumbering your cells by ten to one. These communities wield a big influence over our health, depending on who their members are. Matam Vijay-Kumar found that different species colonise the guts of mice with weakened immune systems, and this shifted membership is linked to metabolic syndrome, a group of obesity-related symptoms that increase the risk of heart disease and type 2 diabetes.
Vijay-Kumar’s mice lacked the vital immune gene TLR5, which defends the gut against infections. Their bowels had 116 species of bacteria that were either far more or less common than usual. They also overate, became fat, developed high blood pressure and became resistant to insulin – classic signs of metabolic syndrome. When Vijay-Kumar transplanted the gut menagerie from the mutant mice to normal ones, whose own bacteria had been massacred with antibiotics, the recipients also developed signs of metabolic syndrome. It was clear evidence that the bacteria were causing the symptoms and not the other way round.
Vijay-Kumar thinks that without the influence of TLR5, the mice don’t know what to make of their unusual gut residents. They react by releasing chemicals that trigger a mild but persistent inflammation. These same signals encourage the mice to eat more, and they make local cells resistant to the effects of insulin. Other aspects of the metabolic syndrome soon follow. The details still need to be confirmed but for now, studies like this show us how foolish it is to regard obesity as a simple matter of failing willpower. It might all come down to overeating and inactivity, but there are many subtle reasons why an individual might eat too much. The microscopic community within our guts are one of them.
Reference: Science DOI:10.1126/science.1179721
The stretchy iron-clad beards of mussels
For humans, beards are for catching food, looking like a druid, and getting tenure. But other animals have beards with far more practical purposes – mussels literally have beards of iron that they use as anchors. The beard, or byssus, is a collection of 50-100 sticky threads. Each is no thicker than a human hair but they’re so good at fastening the mussels to wave-swept rocks that scientists are using them as the inspiration for glue. So they should. The byssus is a marvel of bioengineering – hard enough to hold the mussel in place, but also stretchy enough so that they can extend without breaking.
The mussel secretes each thread with its foot, first laying down a protein-based core and then covering it in a thick protective layer that’s much harder. When Matthew Harrington looked at the strands under a microscope, he saw that the outer layer is a composite structure of tiny granules amid a looser matrix. The granules consist of iron and a protein called mfp-1, heavily linked to one other – this makes the byssus hard. The matrix is a looser collection of the same material, where mfp-is 1 heavily coiled but easy to straighten – this lets the byssus stretch. The granules have a bit of give to them but at higher strains, they hold firm while the matrix continues extending. If cracks start to form, the granules stop them from spreading.
It’s unclear how the mussel creates such a complicated pattern, but Harrington suggests that it could be deceptively simple – changing a single amino acid in the mfp-1 protein allows it to cross-link more heavily with iron. That’s the difference between the tighter granular bundles, and the looser ones they sit among.
Reference: Science DOI:10.1126/science.1181044
Cause of dinosaur extinction
Sixty-five million years ago, the vast majority of dinosaurs were wiped out. Now, a new paper reveals the true cause of their demise – legions of zombies armed with chaingu… wait… oh. Right. An asteroid. You knew that.
More from Mark Henderson at the Times
Reference: Science DOI:10.1126/science.1177265
You are not alone. Even if you’re currently reading this in complete isolation, you are still far from a singular individual. You’re more of a colony – one human, together with microbes in their trillions. For every one of your own genes, your body is also host to thousands of bacterial ones. Some of the most important of these tenants – the microbiota – live in our gut. Their genes, collectively known as our microbiome, provide us with the ability to break down sources of food, like complex carbohydrates, that we would otherwise find completely indigestible.
Peter Turnbaugh from the Washington University School of Medicine has spent his career studying the microbiome. His latest work reveals both tremendous differences and similarities between the bacterial tenants of our digestive systems. Your bowels may be home to very different species of bacteria to mine, but both our sets share a core group of genes.
Turnbaugh likens the situation within our guts to that of islands. Real islands may be home to very different species of animals but all have representatives that perform certain roles; there will always be grazers, predators, insect-eating specialists, fishermen and so on. Across islands, animals approach a set of core lifestyles in different ways, and so it is with the microbiota – every man is an island, home to unique collections of bacteria that nonetheless carry out some core functions. And the further an person’s microbiota strays from this standard template, the more likely they are to be obese.
There is a widespread belief, that being overweight or obese is a question of failing willpower, fuelled in no small part by food, fitness and beauty industries. But if we look at the issue of obesity through a scientific spyglass, a very different picture emerges. Genes, for example, exert a large influence on our tendency to become obese often by influencing behaviour – a case of nature via nurture. But it’s not just our own genes that are important.
In terms of processing food, humans are hardly self-sufficient. Our guts are the home of trillions of bacteria that help to break down foodstuffs that our own cells cannot cope with. Together the genes expressed by these intestinal comrades outnumber our own by thousands of times, and yet we are still largely in the dark what they do.
Over 90% of these bacteria, collectively known as the microbiota, come from just two groups – the Bacteroidetes and the Firmicutes. Now, new research suggests that the proportion of these groups is linked to the risk of becoming obese.
Many measures to curb the obesity epidemic are aimed at young children. It’s a sensible strategy – we know that overweight children have a good chance of becoming overweight adults. Family homes and schools have accordingly become critical arenas where the battle against the nation’s growing waistlines is fought. But there is another equally important environment that can severely affect a person’s chances of becoming overweight, but is more often overlooked – the womb.
Overweight parents tend to raise overweight children but over the last few years, studies have confirmed that this tendency to transcend generations isn’t just the product of a shared home environment. Obesity-related genes are involved too, but even they aren’t the whole story. Research has shown that a mother’s bodyweight in the period during and just before pregnancy has a large influence on the future weight of her children.
For example, children born to mothers who have gone through drastic weight-loss surgery (where most of the stomach and intestine are bypassed) are half as likely to be obese themselves. On the other hand, mothers who put on weight between two pregnancies are more likely to have an obese second child. In this way, the obesity epidemic has the potential to trickle down through the generations, like a snowball rolling its way into an avalanche.
Now, Robert Waterland from the Baylor College of Medicine has demonstrated how the snowball gains momentum by studying three generations of mice that have a genetic tendency to overeat. And using a special diet that was high in folate and other nutrients, he found that he could stop the snowball’s descent and spare future generations of mice from a heightened risk of obesity.
This is a quick follow-up to my other post on fat cells, which as it happens, isn’t the only obesity-related story out today. Another paper found a common genetic variant that increases the risk of obesity in its carriers.
A huge team of researchers scoured the genomes of almost 17,000 European people for genetic variations that are linked to obesity. Until now, only one has been found and it sits within a gene called FTO. This new study confirmed that FTO variants have the strongest association with obesity, but in the runner-up position is another variant near a gene called melanocortin-4 receptor or MC4R.
As fat people have an abundance of fat tissue, the natural assumption is that fat people have more fat cells, or ‘adipocytes‘. That’s only part of the story – it turns out that overweight and obese people not only have a surplus of fat cells, they have larger ones too.
The idea of these ‘fatter fat cells’ has been around since the 1970s. But their importance has been dramatically highlighted by a new study, which shows that the number of fat cells in both thin and obese people is more or less set during childhood and adolescence. During adulthood, about 8% of fat cells die every year only to be replaced by new ones. As a result, adults have a constant number of fat cells, even those who lose masses of weight. Instead, it’s changes in the volume of fat cells that causes body weight to rise and fall.
Kirsty Spalding from the Karolinska Institute in Sweden, together with a large team of international researchers, uncovered several lines of evidence to support these conclusions. Her study is a fascinating mix of cell counting, stomach surgery, radioactive Cold War fallout and a rather surprising use for carbon-dating.