Published November, 12, 2013
GUELPH, Ont. – Emma Allen-Vercoe and her graduate students have come to appreciate the unmistakable odour that hits when you enter their laboratory.
“When we walk in and don’t smell anything, that’s when we begin to worry,” says Allen-Vercoe, a microbial ecologist who has spent almost a decade at the University of Guelph studying what most people can’t wait to flush down the toilet.
Feces provide a window on the vast community of bacteria, fungi and viruses living in the human gut, an ecosystem Allen-Vercoe finds more intriguing than anything in the tropical rain forests or world’s oceans. “It’s the most diverse and densely populated ecosystem on Earth,“ she says.
The human “microbiota” or “microbiome,” as the trillions of organisms are collectively known, is critical to good health. And the microbes do a lot more than help digest food. Mounting evidence indicates they also offer protection against asthma, pathogens, allergies, diabetes and perhaps even certain forms of autism and cancer.
“You mess with it at your peril,” says Allen-Vercoe, who makes a strong case for treating microbes as an ally, not an enemy.
Allen-Vercoe is so intrigued by the internal ecosystem, she eavesdrops on it with the “roboguts” she designed to mimic conditions in the intestines. “You can listen in on how microbes are speaking to each others, and behaving and interacting,” she says.
At the heart of the contraptions are glass bottles, anchored in stainless-steel housing and kept at a toasty 37 degrees Celsius. They are seeded with fecal donations from volunteers, who visit the washroom down the hall and discreetly supply fodder for her experiments.
Allen-Vercoe is quick to joke about her work, which gets lots of attention from the “pooparazzi” – her lab’s name for the news media.
But she is very serious about the way modern life, with its focus on cleanliness, refined foods, and reliance on antimicrobials drugs, is damaging the invisible organisms that live in and on the human body.
The notion that the best microbe is a dead microbe is so pervasive that modern store shelves are lined with cleaners, equipment and toys infused with compounds said to be “antibacterial.” There are even “antimicrobial” staplers and file folders for the office.
“The worry is that being brought up in an average clean household, children are just not getting the exposure to microbes that they should at critical points in development,” says Allen-Vercoe.
More concerning than the antimicrobial consumer products are antibiotic drugs.
While antibiotics can be lifesaving, public health officials are calling for much more prudent use of them in medicine and agriculture.
Allen-Vercoe recently asked the 300 students in one of her microbiology classes at Guelph how many of them made it to university without ever being treated with an antibiotic. “Not one person raised their hand,” she says.
Antibiotics kill off both good and bad bacteria. This can leave people susceptible to weedy microbes such as antibiotic resistant Clostridium difficile, which can cause relentless diarrhea that can be fatal, particularly in older individuals.
“C. diff is very much the poster child for how we’ve messed things up by interfering with the microbiota,” says Allen-Vercoe.
And it is just the most obvious problem.
Scientists are concerned the microbiota is becoming more impoverished with each successive generation.
Work in several labs suggests decades of antibiotics use have altered the microbiota in ways that may be fuelling epidemics of obesity, diabetes, allergies and asthma.
The tiny bacterium Helicobacter pylori, one the few microbes that can live in the harsh acidic environment in the stomach, is one casualty. A century ago, it was the dominant microbe in people’s stomachs, but studies have found less than six per cent of children in the United States, Sweden and Germany now carry the tiny corkscrew-shaped bacterium.
Doctors initially thought it was good to be rid of H. pylori, as it increases the risk of ulcers and stomach cancer. But recent studies show people without the microbe are more likely to have hay fever and allergies. Dr. Martin Blaser at New York University has reported that eradicating H. pylori also affects two key hormones that regulate appetite, which could be helping drive the obesity epidemic.
Antibiotic treatment early in life can also take a toll on microbes that help stimulate development of the infant immune system to differentiate between friendly and harmful organisms, according to research on mice in Brett Finlay’s lab at the University of British Columbia. This might explain why children given antibiotics in their first year tend to have higher rates of allergic asthma. The wheezing and shortness of breath is due to an overactive immune response to things such as harmless microbes, pollen and pet dander.
Finlay’s group is now exploring how antibiotics affect development of children’s microbiota and immune systems as part of the $19-million Canadian Healthy Infant Longitudinal Development (CHILD) study of 3,500 youngsters in B.C., Alberta, Manitoba and Ontario.
Some of the ‘Brown Gold’ that Dr. Emma Allen-Vercoe, Associate Professor, Molecular and Cellular Biology, and her graduate students harvest after growing microbes in “roboguts”, an apparatus that mimics what goes on in the human gut.
Allen-Vercoe decided to explore the internal microbial ecosystem after years of studying pathogens in Britain and Calgary.
“It had been largely ignored,” she says, in part because many gut microbes are unknown and hard to grow in the lab.
Rather than taking the traditional approach and looking at the organisms individually, she cultures microbial communities as they exist in the body.
“Microbes are like teenagers, they like to be with their friends,” says Allen-Vercoe.
Conditions in her “roboguts” mimic those of the lower intestine, with plastic tubing and clamps controlling what goes in and out. They keep out oxygen, which is toxic to many of the microbes, deliver food that comes as an amber mixture, and divert the gassy “farts” to a vent in the ceiling – with limited success.
The odour in the lab simply means the microbes are “healthy and happy,” says Allen-Vercoe.
The “liquid gold” that drips out of roboguts provides insight into what the communities are up to, and what kind of compounds and metabolites they are producing.
Humans’ microbial ecosystems hum along in ways scientists are just beginning to understand. And they can shift dramatically when people develop disorders such as Inflammatory Bowel Disease. The Guelph team is trying to identify the microbes involved and assess the impact of different drugs, hormones and foods.
Allen-Vercoe is also working with researchers at Western University in Ontario on regressive autism, which is associated with gut inflammation and proliferation of certain types of bacteria. These children appear to develop normally as infants but their social and behavioural skills regress by the time they are about three years old.
There might be a “narrow window” when it might be possible to restore a healthy gut microbiota in the children, but Allen-Vercoe says “it might not necessarily fix the cognitive issue.”
Her group also recently found an overabundance of Fusobacterium nucleatum in colon tumors. The bacterium has long been known as an oral microbe that plays a lead roll in dental plaque. Allen-Vercoe is working scientists at the B.C. Cancer Agency to find out what the microbe is doing in colon cancers.
While scientists are linking more and more disorders to the microbiota, Allen-Vercoe cautions against thinking there will be easy solutions.
“To have this idea that we just can carry on as we are and just fix our microbiota every now and again is very short-sighted,” she says, stressing the need to curb use of antimicrobials and better protect our resident microbes.
“They really are vital,” she says.
– Research for this story was funded in part by a journalism award from the Canadian Institutes of Health Research.
Our microbial voyage:
Our relationship with microbes begins when we slip into the world at birth. Infants passing through their mother’s vagina pick up their first microbial passengers when they are coated with “founder” bacteria such as Lactobacillus johnsonii.
Then, breast milk delivers more bacteria along with complex carbohydrates that act like fertilizer, enabling beneficial organisms to take hold in infants’ guts.
The microbial pile-on continues as babies are passed around to friends and family, each with their own unique community of bacteria and fungi on their skin and in their months. It accelerates as babies start crawling around, gumming their toys and petting the family dog and cat.
By age five, children have amassed trillions of bacteria, fungi and viruses – collectively known as the “microbiota” or “microbiome.” The invisible organisms have taken up residence on their skin, and in their mouths, lungs and guts.
The microbiota is so rich that scientists estimate that for every human cell in the body, there are 10 microbes.
They are found from head to toe, but the gut is home to most of them.
“One gram of feces is populated with more microbes than all the people on Earth,” researcher Brett Finlay at the University of British Columbia likes to point out.
Add all the organisms up and they can weigh almost as much as the liver. And scientists say they are just as important.
The microbes help digest food and synthesize key nutrients such as Vitamins B and K. They keep pathogens at bay. Their secretions moisturize the skin. The organisms also interact with their human hosts, stimulating healthy development of the immune system. And they pump out signalling molecules that scientists now suspect affect everything from brain development to weight gain.
The Human Microbiome Project, a $115-million project funded by the U.S. National Institutes of Health, is mapping the genes of all the microbes living in and on more than 240 healthy individuals.
The estimated 100 trillion microbes in and on the average human belong to as many as 1,000 different types or strains. The collection is more diverse in people who live with animals and eat an unrefined diet with plenty of vegetables.
And the microbes collectively have a lot more genetic machinery than their human host – an estimated 100 times more genes. The organisms, some of which can reproduce every 20 minutes, are so adaptable they can help their human hosts deal with new conditions and threats.
“Microbes can download any gene they want,” says Finlay, referring to the way bacteria are constantly swapping and sharing genetic material. This comes in handy when fending off incoming pathogens and toxins.
The risks of Caesarian section:
When Emma Allen-Vercoe’s sister-in-law recently had a caesarean section, she instructed her brother to take a swab of his wife’s vaginal fluid and put it in the baby’s mouth.
Her brother found the advice “horrifying,” says Allen-Vercoe, who did her best to impress on him the importance of the “founder” microbes that infants pick up on their way through the birth canal.
The microbes, she notes, have potentially lifelong effects.
Children born by C-section are at increased risk of asthma, obesity and Type 1 diabetes, disorders researchers now suspect are linked to bypassing the vaginal microbes.
When infants are surgically removed from the womb during C-sections, the first microbes they encounter tend to come from medical staff and their parents’ skin.
“It’s is a very different way of entering the world,” says Vancouver pediatrician Dr. Stuart Turvey. He leads the Vancouver arm of the CHILD study Canadian Healthy Infant Longitudinal Development (CHILD) study of 3,500 youngsters in B.C., Alberta, Manitoba and Ontario exploring several factors – including c-sections and bottle feeding – that may contribute to the asthma and allergies now affecting millions of Canadians.
A study of 24 Manitoba children involved in the project found babies born by elective C-sections had “particularly low bacterial richness and diversity” compared to infants born vaginally. And a small European study, also involving 24 youngsters, published this summer found children born by c-section start life with insufficient intestinal bacteria flora known to protect against allergies.
U.S. researchers have also found vaginal bacteria change during pregnancy with a significant increase in the bacteria Lactobacillus johnsonii, which is normally found in the gut where it produces enzymes that digest milk. Its presence in the vagina ensures the baby will pick up Lactobacillus johnsonii and be ready to digest breast milk.
Turvey says a “paradigm shift is occurring” in understanding the importance microbes play in health. But he says it is too early to make recommendations based on the limited data available.
Allen-Vercoe agrees there is much to learn, but says it is clear the first months of life are critical for acquiring important microbes.
She suggests that women who are having elective C-sections to avoid the pain and unpredictability of natural childbirth should reconsider. And women who need the operation, which is often medically necessary, should try to ensure their babies are exposed to their vaginal fluids.
The idea may become more palatable when a project in Puerto Rico is complete. There, researchers are taking secretions from the mother’s vagina and rubbing them on the face of babies born by C-section. (Puerto Rico’s C-section rate is even higher than Canada’s 27 per cent.)