Gut instincts

00:56, Sep 27 2014
gut instincts
BELLIES AND BIOMES: The 100 trillion fungi, bacteria, protozoa and viruses living in the body outnumber human cells 10 to 1. Collectively, they're known as the microbiome.

Could the way we are born influence how healthy we will be in later life? Nikki Macdonald investigates the influence caesarean births may have and talks to three Kiwis leading research into the links between gut health and diseases such as asthma, obesity and food allergies


Had a gut's full? Consider yourself lucky. Most of us are about one-third short of the full complement.

Imagine an age-old jungle with thousands of animals and plants in perfect balance. Now drop some napalm and watch what happens. Noxious weeds colonise where once there were towering trees. Bugs and animals flee to shade and shelter. The perfect balance might never be restored.

The same could be true of our internal jungle, or microbiome - the miniature bugs that outnumber human cells 10 to 1. Combine 70 years of the indiscriminate killing machines that are broad spectrum antibiotics and the rise of antibacterial everything, and scientists estimate we have lost one-third of our microbiome's diversity.

That is bad, given the emerging science linking an individual's bacterial signature to their susceptibility to the disease epidemic that threatens to make this generation the first to die at a younger age than their parents.


"Our ancient microbiome, which protected us against many of these diseases, is degrading," says Human Microbiome Programme director Martin Blaser, in a new documentary, Microbirth.

"Diversity is going down and that, to an ecologist, is dangerous because diversity protects us", says Blaser, whose book Missing Microbes investigated the role of antibiotic overuse in fuelling our modern diseases.

But what if the problem goes far beyond environmental change, to those first seeds sown on the fertile jungle floor?



Microbirth links the plague of our time - the exponential rise in non-infectious diseases such as asthma, cardiovascular disease, obesity and food allergies - to ever-increasing rates of birth by caesarean section.

It is not as crazy as it sounds.

Research has shown that the tiny guts of babies born by caesarean have different communities of microbes to babies born by vaginal birth; they also have higher rates of childhood asthma, coeliac disease and even slightly higher rates of obesity.

Which does not prove that the one causes the other. However, what is clear is that the adage that babies are born sterile is wrong.

Some studies suggest the placenta contains microbes similar to those in the mouth. That is still controversial but there is general acceptance, thanks in part to the work of Kiwi Jeremy Burton, that the birth canal contains 300-400 microbe species, which "seed" the baby's gut as it passes through.

Bypass that process with a quick snip of the abdomen and the first microbes to reach the baby's gut will instead be those living in the hospital surgery. And that in turn could affect the critical early development of the baby's immune system, as Cornell University professor of immunotoxicology Rodney Dietert points out in Microbirth.

"When a baby comes down the birth canal in vaginal delivery that is the major seeding event. We know that gut microbes in particular are absolutely crucial for what happens in the immune system and the capacity to break down different nutrients and environmental chemicals. That's where the action happens so that is probably the single most important event for deciding whether that baby experiences a life filled with health or one filled with disease."

But it is not just the birth process itself: caesareans are often teamed with antibiotics and delayed breast-feeding, both of which affect the range of microbes available to colonise the baby's gut.

Given that caesarean sections are mushrooming worldwide, the issue is an important one. In New Zealand one in four babies are now born by caesarean, compared with 1 in 9 in 1988. The rate continues to increase every year, with a 4 percentage point increase from 2001 to 2012 alone.

Auckland obstetrician and Auckland University senior obstetrics and gynaecology lecturer Michelle Wise says the biggest factor driving that increase is the rise in complications associated with ever-older mothers. (In 2011, only 13 per cent of women aged under 20 had caesareans, compared with 39.2 per cent of women aged 40 or older.)

Wise says the most alarming thing is that about half the planned rather than emergency caesareans performed are repeat caesareans. So the rate will continue to rise.

The World Health Organisation suggests caesarean deliveries should not exceed 15 per cent of all births.

In the developed world only the Netherlands complies, at 14.3 per cent. Rather than pushing to meet a target, Wise advocates making sure every caesarean is medically required and ensuring women know their options. She runs a clinic to support women who have had one caesarean to try for a subsequent vaginal birth. Eight out of 10 women succeed.



In the absence of any radical medical advances, caesareans will remain an important tool to protect babies and mothers in difficult labour.

But it is not all doom and gloom.

Just realising that caesarean birth might influence a baby's disease-fighting firepower creates opportunities to prevent autoimmune and allergic conditions caused by the immune system mistaking benign bacteria or particular foods for dangerous invaders.

New York researcher Maria Gloria Dominguez-Bello is testing whether inoculating caesarean babies with their mother's vaginal biota immediately after birth can prevent the wrong microbes taking hold in the baby's gut.

Here in New Zealand, Malaghan Institute senior research fellow Elizabeth Forbes-Blom is also investigating the potential links between caesarean birth and disease.

As bizarre as it sounds, she says, she fell in love with gut research on a 2001 summer scholarship at Australian National University.

In the decade since, studying bugs has become mighty trendy and the resulting cutting edge research has revealed three things:

Children born by caesarean section have different gut microbes to children born by vaginal birth.

People born by caesarean have increased rates of non- communicable diseases such as asthma, coeliac disease and type- 1 diabetes.

People suffering from non- communicable diseases have different gut bugs to those who don't.

The big question remaining is how those three things link together.

Given the size of the gut (uncoiled it would fill a studio apartment) and the fact it has more immune cells than anywhere else in the body, it is logical that its inhabitants are linked to the way the immune system operates.

Forbes-Blom reasons that if the pioneer gut microbiota help to train a baby's still-developing immune system, then if the first microbe crop is not the beneficial bacteria seeded through the mother's vagina, they might teach the immune system bad habits.

For example, making it think it needs to attack a humble peanut or dustmite. And everyone knows that bad habits are hard to break.

But if you could get in early and change the kinds of bacteria doing the teaching, there is a chance you could prevent the diseases from taking hold.

"What we need to now work out is what is that window in early life and what are the interactions between which microbes and the immune cells that educate it properly . . . If we can understand this, we have real hope of getting rid of non-communicable diseases."

Forbes-Blom's research centres on experiments on mice with caesarean-type microbiota and mice with microbiota similar to a baby delivered by vaginal birth. By simulating different birth processes, she can work out whether the microbes are being passed on through birth, through the placenta, or after birth.

She can also test whether different microbe populations produce different immune responses to vaccines, or different numbers of specific immune cells.

Although her results are still preliminary, Forbes-Blom has shown it is possible to change the immune response to vaccines by cross-fostering - exposing the pups with caesarean-type microbiota to a mum with natural-type microbiota, and vice versa.

"That's the type of thing we're starting to get really excited about," she says. "If we can put all these things together, instead of creating a tipping point that generates susceptibility to disease, can we create the perfect scenario that means we are at less risk of developing those non- communicable diseases?"



Another Kiwi - a rock star in the microbiome world - is trying to find out what that perfect, healthy community of bugs might look like.

Colorado-based Rob Knight collaborates with Blaser and Dominguez-Bello. He also co- founded the American gut project, which has been running for almost two years and has so far crowd-sourced 4000 poo samples, with another 4000 people signed up.

The idea is to profile as many gut communities as possible and untangle the complex strands of diet, lifestyle, genes and microbes in a quest to understand the link between your bacterial fingerprint and your susceptibility to disease.

Knight's research has also helped show differences in gut microbes between obese and trim people, between people living in different countries and between babies born by vaginal birth and those born by caesarean. Oh, and he invented the software needed to compare two microbial communities. A microbial fingerprint technique he pioneered even appeared on hit TV show CSI: Miami.

In his spare time Knight hangs out in Tanzania taking microbe samples from the hunter-gatherer Hadza people, who breast-feed for two years, have no antibiotics or caesarean deliveries, drink untreated water and eat bug-filled impala stomach completely raw.

"That was amazing," Knight says. "I got to shake the hand of a man who two weeks before had shot a lion with a bow and arrow he made, then ate it with his family."

The idea is to compare the tribe's microbiota to that of modern Westerners and see how our vastly changed diet and sanitised lives have altered our gut bugs. Again, if they can identify what a "healthy" gut microbiota looks like, they can try to find ways to reproduce it.

One delightful option is faecal transplants, which have successfully treated infections of the evil invader Clostridium difficile. Essentially, a donor's good bacteria push out the baddies.

"In mice, it's conclusive that which microbes you have affect which diseases you're susceptible to, from viruses to models of multiple sclerosis," Knight says.

"For humans, the evidence is less clear but it's very likely. In the special case of Clostridium difficile-associated disease, people are manipulating the microbiota right now to cure disease with 95 per cent success rates.

"The question is really which other diseases that we now know the microbiome is linked to will be similarly cured by microbiome- based therapies. Prevention is a very interesting topic but is in an earlier stage of research."

Diet also plays a role. Breast milk contains indigestible sugars, called oligosaccharides, whose sole purpose is to feed the baby's good bacteria. If scientists can work out what kind of food supports which microbes, and which microbes do what, they could find the right diet to support a healthy gut.

That is where Canada-based Kiwi Jeremy Burton comes in. He has been studying health-giving bugs for more than a decade, way back when everyone dismissed it as a waste of time. His research has included pioneering studies into vaginal microbiota. During a stint back in New Zealand at biotech company Blis, he helped develop a probiotic icecream for sore throats.

He is now deputy director of the Canadian Centre for Human Microbiome and Probiotic Research.

If there is a clear link between the absence of a particular microbe or microbes and disease, such as the lack of oxalabacter causing kidney stones, the challenge is to find a way to reintroduce that bug, Burton says.

Faecal transplants or synthetic poop pills are one option, probiotics are another. But at present probiotics are limited to the 0.001 per cent of bacteria cleared for use in the food industry. Other important microbiota might also have the potential to be harmful, making them more difficult to get across regulatory hurdles.

"There's a huge tide of medical problems coming and I think the microbiome is going to play a key part in treatment of that.

"Really, the microbiome information is your genetic information too, it's just that they forgot about it when they did the human genome project.

"We need it, we're just linked to it," Burton says. "In the future there will be a lot of cross-linking that information with what is wrong with you. If it's a microbiome problem, maybe there will be fermenters down in the basement of the hospital where they've got different collections of bugs bubbling away that they're going to dose out to you. That's where I think I see it going."



The 100 trillion fungi, bacteria, protozoa and viruses living in the body outnumber human cells 10 to 1. Collectively, they're known as the microbiome.

About 1000 different microbe species live in the intestine.

Scientists estimate we have lost one-third of the "old friend" microbe species we've grown up with.

Smooching your pet dog helps increase your skin's microbial diversity; smooching your cat doesn't.

Your microbiome can take over a hotel room within hours, wiping out every trace of the previous resident.

The Dominion Post