Good health begins in the gut

UAlberta scientists and clinicians explore how gut bacteria may be key to a healthy life.

For the germaphobes among us, the mere thought of bacteria can be gut-wrenching. But as it turns out, the bacteria in our guts is a key factor to good health.

Scientists at the University of Alberta’s Faculty of Medicine & Dentistry are among Canada’s leading experts on the microbiome—the bacteria residing in our digestive tract. Together they are broadening the understanding of how these micro-organisms in our gut influence our health throughout life, impacting our likelihood of developing allergies, obesity and other serious conditions.

A groundbreaking U of A study shows that babies from families with pets had higher levels of two types of microbes associated with lower risks of allergic disease and obesity.

“There’s definitely a critical window of time when gut immunity and microbes co-develop, and when disruptions to the process result in changes to gut immunity,” said Anita Kozyrskyj, a U of A pediatric epidemiologist and one of the world’s leading researchers on gut microbes.

The study expands on two decades of research that show children who grow up with dogs have lower rates of asthma. According to Kozyrskyj, the findings may one day lead to the pharmaceutical industry creating a “dog in a pill” as a preventative tool for allergies and obesity.

While Kozyrskyj focuses on the early influences affecting gut bacteria in life, other U of A experts like gastroenterologist Dina Kao are making their own mark on the quickly expanding field of microbiome research. Kao’s work focuses on correcting unhealthy gut bacteria.

Could poop be the new scoop?

Kao is one of just a few clinicians across Canada performing fecal transplants to remedy the effects of a compromised microbiome. She has discovered that altered gut bacteria—often caused by the unnecessary use of antibiotics—can lead to serious conditions such as recurrent Clostridium difficile infection. Her research has proven that a fecal transplant from a healthy donor can replenish the microbiome of C. difficile patients with healthy bacteria, and is far more effective than conventional treatments.

“Currently no effective conventional therapy exists for recurrent Clostridium difficile infection,” says Kao. “But fecal transplant can provide a permanent cure for over 90 per cent of patients. You can see the changes in them right before your eyes. It is amazing.”

While the study of gut bacteria is still in its infancy, giant strides are being made at the U of A and beyond. And Kao firmly believes the best is yet to come.

“It’s an open book. And it has tremendous potential.”

Learn more about this topic at the Festival of Health

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This article originally appeared on ualberta.ca and was written by Ross Neitz.

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