More than half your body is not human

More than half of your body is not human, say scientists.

Human cells make up only 43% of the body's total cell count. The rest are microscopic colonists.

Understanding this hidden half of ourselves - our microbiome - is rapidly transforming understanding of diseases from allergy to Parkinson's.

The field is even asking questions of what it means to be "human" and is leading to new innovative treatments as a result.

"They are essential to your health," says Prof Ruth Ley, the director of the department of microbiome science at the Max Planck Institute, "your body isn't just you".

No matter how well you wash, nearly every nook and cranny of your body is covered in microscopic creatures.

This includes bacteria, viruses, fungi and archaea (organisms originally misclassified as bacteria). The greatest concentration of this microscopic life is in the dark murky depths of our oxygen-deprived bowels.

Prof Rob Knight, from University of California San Diego, told the BBC: "You're more microbe than you are human."

Originally it was thought our cells were outnumbered 10 to one.

"That's been refined much closer to one-to-one, so the current estimate is you're about 43% human if you're counting up all the cells," he says.

But genetically we're even more outgunned.

The human genome - the full set of genetic instructions for a human being - is made up of 20,000 instructions called genes.

But add all the genes in our microbiome together and the figure comes out between two and 20 million microbial genes.

Prof Sarkis Mazmanian, a microbiologist from Caltech, argues: "We don't have just one genome, the genes of our microbiome present essentially a second genome which augment the activity of our own.

"What makes us human is, in my opinion, the combination of our own DNA, plus the DNA of our gut microbes."

Listen to The Second Genome on BBC Radio 4.

Airs 11:00 BST Tuesday April 10, repeated 21:00 BST Monday April 16 and on the BBC iPlayer

It would be naive to think we carry around so much microbial material without it interacting or having any effect on our bodies at all.

Science is rapidly uncovering the role the microbiome plays in digestion, regulating the immune system, protecting against disease and manufacturing vital vitamins.

Prof Knight said: "We're finding ways that these tiny creatures totally transform our health in ways we never imagined until recently."

It is a new way of thinking about the microbial world. To date, our relationship with microbes has largely been one of warfare.

Microbial battleground

Antibiotics and vaccines have been the weapons unleashed against the likes of smallpox, Mycobacterium tuberculosis or MRSA.

That's been a good thing and has saved large numbers of lives.

But some researchers are concerned that our assault on the bad guys has done untold damage to our "good bacteria".

Prof Ley told me: "We have over the past 50 years done a terrific job of eliminating infectious disease.

"But we have seen an enormous and terrifying increase in autoimmune disease and in allergy.

"Where work on the microbiome comes in is seeing how changes in the microbiome, that happened as a result of the success we've had fighting pathogens, have now contributed to a whole new set of diseases that we have to deal with."

The microbiome is also being linked to diseases including inflammatory bowel disease, Parkinson's, whether cancer drugs work and even depression and autism.

Obesity is another example. Family history and lifestyle choices clearly play a role, but what about your gut microbes?

This is where it might get confusing.

A diet of burgers and chocolate will affect both your risk of obesity and the type of microbes that grow in your digestive tract.

So how do you know if it is a bad mix of bacteria metabolising your food in such a way, that contributes to obesity?

Prof Knight has performed experiments on mice that were born in the most sanitised world imaginable.

Their entire existence is completely free of microbes.

He says: "We were able to show that if you take lean and obese humans and take their faeces and transplant the bacteria into mice you can make the mouse thinner or fatter depending on whose microbiome it got."

Topping up obese with lean bacteria also helped the mice lose weight.

"This is pretty amazing right, but the question now is will this be translatable to humans"

This is the big hope for the field, that microbes could be a new form of medicine. It is known as using "bugs as drugs".

Goldmine of information

I met Dr Trevor Lawley at the Wellcome Trust Sanger Institute, where he is trying to grow the whole microbiome from healthy patients and those who are ill.

"In a diseased state there could be bugs missing, for example, the concept is to reintroduce those."

Dr Lawley says there's growing evidence that repairing someone's microbiome "can actually lead to remission" in diseases such as ulcerative colitis, a type of inflammatory bowel disease.

And he added: "I think for a lot of diseases we study it's going to be defined mixtures of bugs, maybe 10 or 15 that are going into a patient."

Microbial medicine is in its early stages, but some researchers think that monitoring our microbiome will soon become a daily event that provides a brown goldmine of information about our health.

Prof Knight said: "It's incredible to think each teaspoon of your stool contains more data in the DNA of those microbes than it would take literally a tonne of DVDs to store.

"At the moment every time you're taking one of those data dumps as it were, you're just flushing that information away.

"Part of our vision is, in the not too distant future, where as soon as you flush it'll do some kind of instant read-out and tells you are you going in a good direction or a bad direction.

"That I think is going to be really transformative."

This article originally appeared on bbc.com and was written by James Gallagher

Illustrations: Katie Horwich

A Probiotic That Lasts?

The bacteria in yogurts have largely failed to live up to their hyped health benefits, but there are other microbes that might.

Imagine that you take some North American mice, breed them in captivity for many generations, and then release them in small numbers into a South American jungle. Smart money says that these house-trained creatures wouldn’t last very long. And yet, this is effectively what we’re doing whenever we buy and consume probiotics.

These products — yogurts, drinks, capsules, and more — contain bacteria that supposedly confer all kinds of health benefits. But most of the bacterial strains in probiotics were chosen for historical reasons, because they were easy to grow and manufacture. They aren’t A-listers of the human gut, and they aren’t well-adapted to life inside us.

To make things worse, they’ve been effectively domesticated, having been reared in industrial cultures for countless generations. And they’re delivered at very low concentrations, outnumbered by the bacteria that already live inside us by hundreds or thousands of time.

A sound concept that doesn’t stick

That’s why studies have repeatedly shown that the bacteria in probiotics are more like tourists than tenants — they pass through without settling down. “You’re trying to establish organisms in an ecosystem to which they haven’t evolved,” says Jens Walter, from the University of Alberta. “They don’t possess the adaptations to be successful.”

That’s why probiotics don’t seem to have any effect on the make-up of the microbiome — the community of microbes that lives within us. It’s also why these products have been so medically underwhelming. The most discerning reviews suggest that they are useful for treating some kinds of infectious diarrhea, but little else.

And over the last decade, European Union regulators have been so unimpressed by the evidence behind probiotics that they banned every single health claim that appeared on these products’ packaging — including the word “probiotic” itself.

The concept is sound, though. We know that the bacteria in our microbiome are important for our health, and that changes in the microbiome have been linked to many conditions including inflammatory bowel disease, colorectal cancer, diabetes, and more. So it should be possible to improve our health by taking the right microbes. The problem is that we do so in a crude and naïve way. These are living things and we are ecosystems. You can’t just introduce the former into the latter and assume they’ll take hold. You need to know why they might succeed or fail. 

Unexpected results

That’s what Walter and his team have started to do. They focused on a specific strain of Bifidobacterium longum, which is a common, stable, and dominant part of the human gut. María Maldonado-Gómez, from the University of Nebraska, asked 23 volunteers to take daily doses of either B. longum or a placebo pill, and checked their stool for signs of the strain’s DNA.

In most of the volunteers, the bacterium disappeared within the first month or even the first week.  But in a third of them, it persisted, and for more than half a year in some cases. Unlike normal probiotics, this strain seemed to establish a permanent foothold.

“I never expected that,” says Walter. “Even with part of our core microbiome, I thought that our resident strains would outcompete the new one.”

In a way, they did. By comparing the volunteers’ microbiomes, Maldonado- Gómez showed that his B. longum strain was less likely to settle down if its new hosts already had B. longum strains of their own. That makes sense: Closely related microbes should be more similar, and thus more likely to compete for the same nutrients, resources, or living spaces. If many kinds of B. longum are already present, there are few niches for an incoming strain to fill.

Maldonado-Gomez also found that the ingested strain was more likely to wash out if a volunteers’ microbiome carried a few dozen particular bacterial genes, the vast majority of which are involved in breaking down carbohydrates and other nutrients. Again, this makes sense: If the native microbes are using these genes to digest whatever food is available, there’s nothing for an immigrant strain to eat.

These results show that it is possible to turn a swallowed microbe into a permanent part of the gut, and they hint at the type of factors that make for successful colonisation.

“I’m excited,” says Walter. “I think it really does show that we might be able to modulate gut ecosystems, by going in and establishing certain microbes. We didn’t look at health, and we’re still trying to identify what microbiome configurations are associated with disease. But if an individual misses or loses strains that are important for their health, it could be possible to redress that.” 

Ecosystem first

“The smart way to administer probiotics is to look at a person’s existing microbial ecosystem first,” says Emma Allen-Vercoe, from the University of Guelph. “Are all the engine parts present and running as they should?  If not, can we provide a missing part by giving a probiotic that possesses it? Can we predict how this newly introduced part will integrate into the engine?”

That’s a savvy and personalised approach to probiotics, with ecology at its heart — very different to the blundering, one-size-fits-all approach that companies currently take.

The success of this personalised approach depends on working out, on an individual basis, what niches in the gut are vacant and which strains are best at filling them. “But what if you could create a niche that only your strain could access?” asks Sean Gibbons, from MIT. Several scientists, he notes, are creating cocktails that contain both a probiotic microbe and a food source that only that microbe can eat — a so-called prebiotic.

“As long as the prebiotic was consumed in the diet, the probiotic would stick around,” says Gibbons. “If the prebiotic were removed, the probiotic would be washed out of the gut.”

Such a strategy might help to address concerns about giving people microbes that are specifically meant to persist in the body. Current probiotics have a fantastic safety record, but perhaps that’s because of their transience. If we switch to strains that are better colonisers, it might lead to unintended consequences.

Then again, there was no evidence of that in Walter’s study. The newcomer strain didn’t displace any of the volunteers’ native microbes, in the way that invasive species like fire ants or cane toads do. It didn’t affect the volunteers’ health, either.

Still, Walter worries that the use of better-colonising strains would lead to inappropriately harsh regulatory hurdles. He feels that the risks of ingesting core members of the microbiome are very small. “We’re already doing that with fecal transplants, and we introduced bacteria into our bodies all the time from our surroundings,” he says.

For now, such talk is moot, because the era of precision microbiome medicine still seems a long way off. “The findings need to be replicated in larger studies,” says Nadja Kristensen, from the University of Copenhagen. And while the study reveals why bacteria might colonise healthy humans, it’s unclear if the same principles would apply to sick people with disturbed microbiomes.

Walter’s study also looked at just one strain of B. longum, which is being developed by the Irish company Alimentary Health as a probiotic. Many other strains exist and they behave very differently.

“The company has another B. longum on the market, and they know for a fact that it doesn’t persist,” he says. “I would hope and anticipate that we’d see more studies that are similar to ours, using core members of the microbiome. We’re really just at the beginning.” 

By Ed Yong

Source: The Atlantic

How Your Social Life Changes Your Microbiome

Every hug, handshake, and hip-check sends the tiny communities that live inside us back and forth.

Social contact can clearly spread disease: That’s why we lean away from snotty hugs, tell sick colleagues to go home, and quarantine people during epidemics. But the germs behind infectious illnesses are but a tiny fraction of our full microbiome—the microbes that share our bodies. Most of these are harmless, perhaps even helpful. And they can hop between individuals, too.

A growing number of studies, including two recent ones with chimps and baboons, have shown that social interactions affect the composition of the microbiome. Through hugs, handshakes, and even hip-checks, we translate our social networks into microbial ones, transferring benign or beneficial microbes to our neighbors, and acquiring theirs in return.

This means that there’s a “pan-microbiome”—a meta-community of microbe species that spans a group of hosts. If you compare your microbiome to your private music collection, the pan-microbiome is like the full iTunes store, and every handshake is an act of file-sharing.

To study how social ties affect the microbiome, you’d ideally want to track people over long periods

There’s some evidence that humans share microbes through physical contact. In one study, people who share living quarters end up with similar microbes. In another, the skin microbes of opposing roller-derby teams converge during a game. But these were snapshots. To study how social ties affect the microbiome, you’d ideally want to track people over long periods—everything from the friends they hung out with to the bacteria in their poop. “You’d have to invade their privacy to an extent that most people probably wouldn’t put up with,” says Andrew Moeller from the University of California, Berkeley.

So instead, he turned to chimps.

Since Jane Goodall’s pioneering work in the 1960s, scientists have constantly observed the Kasakela chimpanzee community in Tanzania's Gombe National Park. They’ve recorded their interactions, and collected stool samples. Using some of this data, Moeller showed that the chimps’ gut microbes are mainly passed horizontally from peer to peer, rather than vertically from parent to child. Although they get their first microbes from their moms, these are eventually overwhelmed by those they pick up from friends.

During seasons when the chimps were more sociable, their microbiomes started to converge. And the most sociable individuals, those who spent most time grooming, touching, or otherwise hanging out with their peers, had the richest diversity of species in their guts.

"Our major exposures are probably each other"

Jenny Tung and Elizabeth Archie found similar trends among two groups of wild baboons in Kenya’s Amboseli National Park. Those that groomed each other more frequently ended up with more similar microbiomes. As a result, the two groups ended up with their own distinctive communities, even though they lived in overlapping areas and ate the same food. Their separate social networks carved a gulf between their microbial communities.

“These animals are eating food covered in dirt and drinking from muddy waterholes, but despite that, we saw signatures of contact with other animals,” says Archie. “You could argue that the effect would be even stronger in humans because we live in such sterile environments. Our major exposures are probably each other.”

These results have important implications. If chimps and baboons (and possibly humans) just inherited microbiomes vertically, they would naturally lose some members because of random events, like dietary upheavals. But if they pass microbes through contact, they ensure that species which disappear from an individual still exist within the wider pool—the pan-microbiome. (And with chimps, it's more like the pan-Pan­-microbiome.) “The propagation of microbes through social interaction may be one of the ways in which diversity is maintained in the microbiome over very long evolutionary timescales,” says Moeller.

The benefits of picking up helpful microbes might even have helped to drive the evolution of social living in the first place. This idea was proposed by Michael Lombardo in 2008; he predicted that if animals get microbes from their peers, they’re more likely to have a more complex social system that regularly brings them into close contact with their contemporaries.

The hypothesis makes intuitive sense and some creatures seem to fit the pattern well. By eating each others’ poop, bumblebees pick up microbes that protect them from parasites; termites do the same through anal licking, and both insects live in cooperative colonies. “Bees have distinct microbiomes, but asocial wasps don’t as much,” adds Moeller. “Primates are some of the most social mammals and have these very consistent microbiomes that track host lineages.”

Still, Lombardo’s hypothesis “is pretty much speculation at this point,” says Moeller. “We’d need to map degree of sociality to some measure of microbial diversity across the tree of life.”

By Ed Yong

 Source: The Atlantic

Gut Microbiota: How it Affects Your Mood, Sleep and Stress Levels

The gut microbiota is the community of bugs, including bacteria, that live in our intestine. It has been called the body’s “forgotten organ” because of the important role it plays beyond digestion and metabolism.

You might have read about the importance of a healthy gut microbiota for a healthy brain. Links have been made between the microbiota and depression, anxiety and stress. Your gut bacteria may even affect how well you sleep.

But it can be difficult to work out exactly how far the science has come in this emerging field of research. So what evidence is there that your gut microbiota affects your brain?

How does your gut talk to your brain?

When you’re healthy, bacteria are kept safely inside your gut. For the most part, the bacteria and your gut live in harmony. (The gut has been known to nurture or even control the behaviour of the bacteria for your well-being.)

So how do the bacteria get their signal out?

The best evidence is that the normal channels of communication from your gut are being hijacked by the bacteria.

The gut has a bidirectional relationship with the central nervous system, referred to as the “gut-brain axis”. This allows the gut to send and receive signals to and from the brain.

A recent study found that the addition of a “good” strain of the bacteria lactobacillus (which is also found in yoghurt) to the gut of normal mice reduced their anxiety levels. The effect was blocked after cutting the vagus nerve – the main connection between brain and gut. This suggests the gut-brain axis is being used by bacteria to affect the brain.

This link was clarified in a study where bacterial metabolites (by-products) from fibre digestion were found to increase the levels of the gut hormone and neurotransmitter, serotonin. Serotonin can activate the vagus, suggesting one way your gut bacteria might be linked with your brain.

There are many other ways gut bacteria might affect your brain, including via bacterial toxins and metabolites, nutrient-scavenging, changing your taste-receptors and stirring up your immune system.

A recent study found that the addition of a “good” strain of the bacteria lactobacillus (which is also found in yoghurt) to the gut of normal mice reduced their anxiety levels.

How can the gut affect your mental health?

Two human studies looked at people with major depression and found that bacteria in their faeces differed from healthy volunteers. But it’s not yet clear why there is a difference, or even what counts as a “normal” gut microbiota.

In mouse studies, changes to the gut bacteria from antibiotics, probiotics (live bacteria) or specific breeding techniques are associated with anxious and depressive behaviours. These behaviours can be “transferred” from one mouse to another after a faecal microbiota transplant.

Even more intriguingly, in a study this year, gut microbiota samples from people with major depression were used to colonise bacteria-free rats. These rats went on to show behavioural changes related to depression.

Stress is also likely to be important in gut microbiota and mental health. We’ve known for a long time that stress contributes to the onset of mental illness. We are now discovering bidirectional links between stress and the microbiota.

In rat pups, exposure to a stressor (being separated from their mums) changes their gut microbiota, their stress response, and their behaviour. Probiotics containing “good” strains of bacteria can reduce their stress behaviours.

How gut microbiota affects your mood

Medical conditions associated with changes in mood, such as irritable bowel syndrome (IBS) and chronic fatigue syndrome (CFS), might also be related to gut microbiota.

IBS is considered a “gut-brain disorder”, since it is often worsened by stress. Half of IBS sufferers also have difficulties with depression or anxiety.

Ongoing research is investigating whether gut bacteria are one reason for the mood symptoms in IBS, as well as the gastrointestinal pain, diarrhoea and constipation.

Similarly, CFS is a multi-system illness, with many patients experiencing unbalanced gut microbiota. In these patients, alterations in the gut microbiota may contribute to the development of symptoms such as depression, neurocognitive impairments (affecting memory, thought and communication), pain and sleep disturbance.

In a recent study, higher levels of lactobacillus were associated with poorer mood in CFS participants. Some improvements in sleep and mood were observed when patients used antibiotic treatment to reduce gut microbial imbalance.

The exact contributions of stress and other factors such as intestinal permeability (which allows nutrients to pass through the gut) to these disorders are not understood. But the downstream effects seem to be involved in IBS, inflammatory bowel conditions, CFS, depression and chronic pain.

How our gut affects our sleep

Our mental health is closely linked to the quality and timing of our sleep. Now evidence suggests that the gut microbiota can influence sleep quality and sleep-wake cycles (our circadian rhythm).

A study this year examined patients with CFS. The researchers found that higher levels of the “bad” clostridium bacteria were associated with an increased likelihood of sleep problems and fatigue, but this was specific to females only. This suggests that an unbalanced gut may precipitate or perpetuate sleep problems.

There is emerging evidence that circadian rhythms regulate the gut immune response. The effect of immune cells on the biological clock could provide insights into the possible bidirectional relationship between sleep and the gut. For example, data from animal studies suggests that circadian misalignment can lead to an unbalanced gut microbiota. But this effect can be moderated by diet.

There is growing concern that disruptions to our circadian timing of sleep leads to a range of health issues, such as obesity, metabolic and inflammatory disease, and mood disorders. This is particularly important for shiftworkers and others who experience changes to their sleep/wake patterns.

For example, data from animal studies suggests that circadian misalignment can lead to an unbalanced gut microbiota. But this effect can be moderated by diet. 

What this means for treatment

In terms of using interventions directed at the gut to treat brain disorders – so called “psychobiotics” – there is a lot of promise but little clear evidence.

Probiotic (live bacteria) treatments in mice have been shown to reduce cortisol, an important stress hormone, and decrease anxious and depressive behaviours.

But there are very few studies in humans. A recent systematic review of all the human studies showed the majority do not show any effect of probiotics on mood, stress or symptoms of mental illness.

On the plus side, large studies show us that people who eat a balanced diet with all the usual good stuff (fibre, fresh fruit and vegetables) have lower rates of mental illness as adults and adolescents.

Clearly, diet affects both the gut microbiota and mental health. Research is ongoing to see whether it is a healthy gut microbiota that underlies this relationship.

A healthy gut microbiota is linked to a healthy brain. However there are only a handful of human studies demonstrating real-world relevance of this link to mental health outcomes.

There is still a way to go before we can say exactly how best to harness the microbiota in order to improve brain function and mental health.

This article originally appeared on The Source and was written by By 

Paul Bertrand, RMIT University, Amy Loughman, RMIT University, Melinda Jackson, RMIT University