Microbiologist Emma Allen-Vercoe studies the 1,000 bacterial species that inhabit your “inner ecosystem” - from mouth to bowel
Story by Andrew Vowles / Photos by Martin Schwalbe
The Poopy Lab does have a distinctive smell, but you get used to it, say these U of G researchers, from left: Eric Brown, Kathleen Schroeter, Jackie Strauss, Emma Allen-Vercoe, Chris Ambrose, Julie McDonald, Mike Toh and Michelle Daigneault.
Jackie Strauss got sick at age 15. It took seven years of inconclusive tests before she ended up in surgery and was finally diagnosed with Crohn’s disease. By then, she was doing undergrad studies at her hometown University of Calgary. That degree took six years to complete. Referring to flare-ups that might be triggered by certain foods, stress or even a cold, Strauss says: “Most of my undergrad was spent struggling, trying to cope with the symptoms and not able to understand.”
That was the bad news. The good news came when she started an undergrad research project in a class taught by microbiologist Emma Allen-Vercoe. By then, Allen-Vercoe had spent four years in Calgary as a post-doc, following her own studies in England. As a newly minted faculty member at U of C, she was launching a research program to learn about gut bacteria and, specifically, how those bugs contribute to inflammatory bowel disease (IBD). Referring both to her supervisor’s research topic and to her research acumen, Strauss says: “Emma’s the main reason I decided to go into grad school. IBD research is important to me because I have a connection with it.”
Plans would soon change for both of them. When Allen-Vercoe moved to Guelph as a professor in the Department of Molecular and Cellular Biology (MCB) in late 2007, Strauss and others came with her. “Research has brought meaning to my suffering. I can live with this horrible disease and still accomplish things. You can still live your life,” says Strauss.
Just inside the door of Allen-Vercoe’s lab in the science complex is a whiteboard where someone has written this line: “The Poopy Lab, where lab stools are not what you expect.”
It’s true. Researchers here are studying surprisingly varied aspects of gut microflora. Those studies take the team from one end of the gastrointestinal tract to the other, and beyond. A primary focus, of course, is learning about IBD. Covering both Crohn’s and ulcerative colitis, IBD affects about 200,000 Canadians, has no cure, and costs this country an estimated $1.8 billion a year in medical and indirect costs.
But the Guelph scientists’ studies also take them into gum and other mouth diseases, probiotics and even autism, all using a suite of research tools, including a made-in-Guelph “robo-gut,” that is nearly unrivalled in Canada.
More bacteria live inside your gut than there are people living on Earth. Up to 1,000 different bacterial species inhabit your GI tract, and your own microbial melange ─ Allen-Vercoe calls it a “poo print” ─ remains with you throughout life. Says Eric Brown, a fourth-year microbiology student working in her lab: “We’re like a big ecosystem of bacterial and human cells.”
Call it an inner ecosystem, says Allen-Vercoe, one whose workings are as complicated as those of any rainforest on the planet. “It’s becoming increasingly clear that our gut microflora are key to our overall health, yet very little is known of the ecology and physiology of these organisms and their interactions with host cells.” She believes those bugs are also a key to understanding disease. “If it’s a healthy rainforest, and you throw in some perturbation, the ecosystem adapts. But if you start stripping out species and throw stress in, the ecosystem collapses.”
Take ulcerative colitis, known to be associated with lower bacterial diversity in the colon. Researchers don’t know what causes the disease. But they know that stress can trigger or worsen inflammation and ulcers in the lining of the colon and rectum. Allen-Vercoe is studying the role of the stress hormone norepinephrine on intestinal bugs. Learning which bacterial species trigger IBD might help in finding new treatments. Although antibiotics are available, the drugs may wipe out good and bad bugs indiscriminately, eventually causing more trouble.
Although she has used only samples from healthy people so far ─ she brought samples from Calgary, and she’s now receiving more from the British Columbia Cancer Agency ─ Allen-Vercoe plans to team up with a Guelph gastroenterologist to obtain stool samples from his patients. Adds Dr. Naoki Chiba: “We’re trying to understand the disease better so that hopefully we can target treatment for it down the road. We don’t have a cure for the disease.”
Besides the Poopy Lab, the real guts of the enterprise are housed in a separate lab one floor up (placed there to keep the odour farther away from neighbours). PhD student Julie McDonald, B.Sc. ’09, and lab technicians Chris Ambrose and two-time Guelph graduate Michelle Daigneault, B.Sc. ’06 and M.Sc. ’09, have spent the past year assembling and testing the robo-gut, technically called a chemostat. All stainless steel, glassware and plastic tubing under computer control, the assembly mimics the airless environment of the large intestine, like human innards on a lab bench.
It’s actually a collection of robo-guts whose six glass flasks each hold about two cups of liquid distilled from stool samples. Having mastered flow rates, retention time and other parameters, the researchers can run cultures under precise conditions during eight-week cycles to compare, say, samples containing norepinephrine against untreated controls.
Eyeing the brown liquid churning away one morning last fall, Allen-Vercoe says: “It seems obvious, but it’s very difficult to do. Everyone’s gut is different.” McDonald studied biochemistry and microbiology at Guelph before starting grad work. “I find it so fascinating that something people don’t think about ─ bacteria in your gut ─ has a major impact on our daily lives.” She tries to emphasize the science rather than what she calls the “uck factor” of her studies. “I try not to say I work with poop; it turns people off.”
Kathleen Schroeter remembers her own childhood fascination with a different kind of bug. She used to suffer from ear infections as a child and recalls hearing her dad ask the doctor about antibiotic resistance. After her B.Sc. here at Guelph, she began her master’s degree, studying gut biofilms. Those mats of clumped-up bacteria can be a nuisance when cleaning the chemostat after a run ─ or a potential health hazard if pathogenic bacteria use biofilms to hide out from antibiotics. But in a project also involving MCB professor Cezar Khursigara, she is looking to see whether biofilms might help improve health. Learn about how bacteria form biofilms, she says, and we might use them to retain good bugs longer, like the probiotic organisms in yogourt. “We’ve all seen the Activia commercials,” says Schroeter.
More bacteria live inside your gut than
there are people living on Earth, say
grad student Kathleen Schroeter, left,
and Prof. Emma Allen-Vercoe.
Back up the gut far enough, of course, and you arrive at the mouth. There, a bug called Fusobacterium nucleatum can cause periodontitis, gingivitis and plaque ─ all inflammatory processes similar to IBD reactions. “Many Crohn’s patients have mouth problems,” says Allen-Vercoe. The U of G researchers will compare strains of “Fuso” from the mouth and the gut. Early genetics studies show that those bugs differ.
The team has also found evidence that IBD patients have more F. nucleatum growing in their GI tracts and more virulent strains of the bug than do control patients without the disease. They hope to find bacterial genes that might serve as markers to provide clues about what causes the disease. Allen-Vercoe aims to obtain samples from dental patients through faculty members at the University of Toronto. That’s a new kind of partnership for both sides. “Dentists don’t speak to gastroenterologists.”
Even less likely might be the notion of GI doctors talking to neurologists. But in what Allen-Vercoe calls a bizarre turn for her studies, she’s now looking at possible connections between gut microbes and nervous disorders, specifically autism. Other researchers have found that gut bacteria in children with autism differ from those in healthy kids. It’s also known that autistic kids often require unusual amounts of antibiotics early in life for ear infections and other problems, often while their GI tract is still assembling that individual “poo print.”
Bacteria produce all kinds of toxic products, says PhD student Mike Toh. “Maybe something from the bug is affecting the brain.” He’s using zebra fish to study how products secreted by gut microbes might affect development. His co-supervisor, MCB professor Terry Van Raay, normally uses the small, fast-growing and transparent fish to study how malfunctions in cell signaling pathways can lead to diseases such as cancer.
Toh also expects to employ the robo-gut to model the GI tract of autism patients and the effects of adding, say, hormones or antibiotics. For this project, Allen-Vercoe is investigating diet-disease connections with autism researchers at the University of Western Ontario and with microbiologists at the University of California, Los Angeles. “It’s a meeting of minds between developmental biology and microbiology,” she says.
In another meeting of minds, she’s one of only a few Canadian researchers working on the international human microbiome project, intended to catalogue the genomes of all microbes found in or on the human body. Funded by the United States National Institutes of Health (NIH), she’s growing and shipping DNA from bacterial strains to the Broad Institute in Cambridge, Mass. There, researchers sequence the material to gain clues about how those strains affect health and disease, and to apply genomics to medicine.
In a 2010 paper published in the prestigious journal Science, the research team reported finding novel kinds of bacterial proteins and said they expected to find many more. “It is our ultimate goal to sample the human microbiome as completely as possible,” says Allen-Vercoe, who is using NIH funding to develop techniques for sifting out and growing rare bacterial species from fecal samples ─ effectively “culturing the unculturable,” as she describes it.
Growing up in England, Allen-Vercoe had planned to become an astrophysicist, but her math wasn’t good enough. She was studying biochemistry at the University of London when she discovered a new world living on Petri plates. “I view a microscope as a very small telescope looking in the other direction,” she says. After a PhD at the U.K.’s Open University and the Centre for Applied and Microbiological Research (now the Health Protection Agency), she came to Canada. With her came her husband and lab technician, Chris Ambrose, and their oldest daughter, Phoebe; another daughter, Zoë, was born in Canada. “We often talk about poop over dinner,” she says. But there is a limit: “I can talk about the science all I like but not any of the day-to-day administrative stuff.”
She’s also encouraged by the Crohn’s and Colitis Foundation of Canada (CCFC) to discuss her work; the area chapter calls her up for occasional public lectures. Last fall, she spoke to two patient groups in southern Ontario. “They make it real,” says Allen-Vercoe, who also receives CCFC funding for her research.
As both a patient and a researcher, Jackie Strauss knows about making it real. After she finishes her doctorate in 2011, she hopes to continue her studies, perhaps by completing medical school and combining clinical and research work. That route might take her back to Calgary, where her husband teaches public school. Over the phone one day last fall, he told her about two students in his class with Crohn’s disease. One mom had shared her worries about her daughter’s prospects. Strauss smiles as she recalls her husband’s words: “‘I told them about you doing your PhD.’” That’s the kind of thing that motivates her research, she says, “to bring hope to other kids with this disease.”