Office: SCIE 3252
Lab: SCIE 3204
I began my research career with undergraduate and graduate studies at the Central Veterinary Laboratories (now Veterinary Laboratories Agency) and the Centre for Applied and Microbiological Research (CAMR, now the Health Protection Agency), UK, under the direction of Prof. Martin Woodward. There, I studied the enteric pathogen Salmonella enterica serovar Enteritidis, and developed a sound appreciation of the many obstacles that a enteric pathogen must overcome in the gut in order to cause disease. I became fascinated by the huge arsenal of virulence factors required by enteric pathogens in order to survive and proliferate in the gut environment.
I spent a brief postdoctoral period at CAMR, learning to work with technically challenging pathogens such as Mycobacterium tuberculosis and Campylobacter jejuni, before I relocated to Canada in 2001 to start a postdoctoral position at the University of Calgary, under the joint direction of Drs. Rebekah DeVinney and Mike Surette. Here I worked on Enteropathogenic and Enterohemorrhagic E. coli (EPEC and EHEC), using cell and molecular biology techniques to probe the fascinating interactions of their type III secretion systems with host cells.
I had always been interested in learning more about the normal microbial population inside the human gut, and in 2004 I was fortunate enough to win a Fellow-to-Faculty Transition award through the Canadian Association of Gastroenterology. This award allowed me to develop an independent research program aimed at the study of the normal human microflora and its influence on human health and disease, a program that I brought with me to Guelph in December 2007.
B.Sc. (Hons) Biochemistry, University of London
Ph.D. Molecular Biology, Open University in conjunction with CAMR, UK Post-doctoral fellow, University of Calgary
Research in my laboratory is focused on the study of the normal human gut microflora, both in disease and in health. The research can be loosely divided into several main areas centered on fundamental questions in the field of microbial ecology of the gut:
1. WHAT GROWS THERE?
The microbial world inside the human gut, though not without an intrinsic 'ick' factor, is a fascinating place, brimming with diversity on an enormous scale, but yet very poorly understood. Whilst molecular signatures have shown that the microflora community within the gut can contain many hundreds of bacterial species, only a small percentage of these species are understood in terms of their biology. The lack of knowledge in this area stems from the fact that, as yet, the conditions required to culture most of the bacterial species resident in the human gut are not understood. In my laboratory, we are developing new techniques to culture and study novel bacterial species from the gut in order to better understand how these species might contribute to the remarkable homeostasis of the microflora community as a whole. Central to our research approach, we have developed a continuous culture system to model the bacterial communities within the distal gut, the most densely populated part of the human body in terms of microbes. Dubbed the Robogut, our model contributes to many of the projects within the lab.
Click this link to download a recent piece featuring this work on CBC's Quirks and Quarks' radio show.
We collaborate closely with Dr. Cezar Khursigara within MCB, and with his group we are developing cutting-edge methods to image and characterize microbial interactions within the gut, with a particular emphasis on understanding the interplay of the normal human flora with introduced probiotic bacteria.
We have an extensive collaboration with the Broad Institute in Cambridge, Massachusetts, whereby we have provided, and continue to provide, a significant number of the bacterial isolates requested for genome sequencing through the Human Microbiome Project.
2. WHICH BACTERIAL SPECIES OF THE NORMAL MICROFLORA CAN CONTRIBUTE TO DISEASE?
In a healthy person, despite the constantly changing environment within the gut, the resident microflora maintain a largely homeostatic balance that is unique to the host. It is becoming increasingly clear that when this balance is shifted, so-called dysbiosis, the consequences to the host can be highly detrimental. My lab studies 4 key diseases with connections to the gut microflora: Inflammatory Bowel Disease (IBD), regressive (late-onset) autism, recurrent (refractive) Clostridium difficile infection (CDI) and colorectal cancer.
IBD is an umbrella term for two debilitating diseases; Crohn's Disease (CD) and Ulcerative Colitis (UC). These diseases are characterized by the formation of gut lesions that are somehow triggered by dysbiosis of the microflora. A large part of the research in our lab is focused on determining which species, or groups of species, of the gut microflora can behave pathogenically towards the host, and how. We are also using the Robogut to study the contributions of environmental factors, such as drugs, hormones and dietary components, to microflora dysbiosis.
Regressive autism is a form of autism spectrum disorder that is characterized by apparently normal development in infancy followed by a sudden regression of social and behavioural skills, usually between 24-36 months of age. In most cases, disturbances and inflammation in the gut are also seen, and several studies have shown an apparent dysbiosis within the gut microbiota of these patients, with certain bacteria belonging to select groups of bacteria predominating. We are working to try to further characterize the microflora of autistic patients, and to determine whether certain bacterial products may somehow be involved in the etiology of this distressing condition. This work is carried out in conjunction with our collaborators at the Kilee Patchell-Evans Autism Research Group at the University of Western Ontario, led by Dr. Derrick MacFabe.
CDI is an infection of particular and growing concern in the hospital setting, causing pain and serious diarrhea in affected patients. C.difficile usually infects patients who have recently had a course of antibiotics, stripping them of their normal gut microflora and allowing space for the pathogen to flourish. Ironically, the current treatment for CDI is a further course of antibiotics to target the C.difficile. Unfortunately, C.difficile can be very difficult to eradicate in this way, and some patients end up with a recurrent C.difficile infection that they are unable to clear, leaving them with no option but to take long-term doses of expensive antibiotics. Fecal transplants offer a potential solution to this infection, by restoring normal flora and displacing the pathogen; however these carry a fairly high degree of risk themselves due to the potential presence of unknown pathogens in donor stool, and as well the procedure is messy and unpleasant. We are working to produce a defined multi-species probiotic – a synthetic stool treatment that we call "RePOOPulate" – to overcome the problems of fecal transplants, while still offering a potential cure for CDI. This work is being carried out in conjunction with our clinical collaborators at Queen’s University/Kingston General Hospital.
Click on this link to download a recent Medical Post article describing this work.
Click on this link to view a recent CTV The National piece that describes the use of RePOOPulate to treat a severely ill CDI patient.
Colorectal cancer is one of the leading forms of cancer in the world. Recently, in collaboration with the BC Cancer Agency, our lab has helped to demonstrate the overabundance of a particular anaerobic species, Fusobacterium nucleatum, in colorectal cancer tumours. This fascinating finding has opened the door to further studies that are underway to try to characterize the role that this enigmatic species may have in disease.
Research Funding Sources
Crohn's and Colitis Foundation of Canada, (CCFC)
National Institutes of Health, (NIH)
US Department of Defense Congressionally Directed Medical Research Program (CDMRP)
Physician’s Services Incorporated (PSI)
The Southeastern Ontario Academic Medical Organization (SEAMO)
Canadian Institutes of Health Research, (CIHR)
Canada Foundation for Innovation, (CFI)
Ontario Ministry of Research and Innovation, (OMRI)
Ontario Ministry of Agriculture, Food and Rural Affairs, (OMAFRA)
Natural Sciences and Engineering Research Council (NSERC)
Canadian Association of Gastroenterology
Crohn's and Colitis Foundation of Canada
Canadian Society of Microbiologists
American Society for Microbiology
International Society for Microbial Ecology
Anaerobe Society of the Americas
Selected Publications (from last 5 years)
Allen-Vercoe, E. and Petrof, E.O. Artificial stool transplantation: progress towards a safer, more effective and acceptable alternative. Expert Review of Gastroenterology & Hepatology. Accepted, in press.
Toh, M., Allen-Vercoe, E., Daigneault M., Goodyear, M., Van Raay, T. Colonizing the embryonic zebrafish gut with anaerobic bacteria derived from the human gastrointestinal tract. Zebrafish. Accepted, in press.
Petrof, E.O., Gloor,G.B., Vanner,S.J., Weese,S.J. Carter, D., Daigneault, M.C., Brown, E.M., Schroeter, K. and Allen-Vercoe, E. Synthetic stool transplant therapy for the eradication of Clostridium difficile infection: "RePOOPulating" the gut. Microbiome. 1:3 (9 January 2013, highly accessed)
Petrof, E.O, Claud, E.C., Gloor, G.B. and Allen-Vercoe, E. Microbial Ecosystems Therapeutics – a New Paradigm in Medicine? Beneficial Microbes, 2013 Mar 1;4(1):53-65.
Shahinas, D., Silverman, M., Sittler, T., Chiu, C., Kim, P., Allen-Vercoe, E., Weese, J.S., Wong, A., Low D.E., Pillai, D.R. Changes in microbial diversity associated with fecal transplantation based on 16S deep sequencing. MBio. 2012 Oct 23;3(5).
Allen-Vercoe, E., Daigneault, M., White, A.P., Panaccione, R., Duncan, S., Flint, H., O’Neal, L. and Lawson, P. Anaerostipes hadrus comb. nov., a dominant species within the human colonic microbiota; reclassification of Eubacterium hadrum Moore et al. 1976. Anaerobe. 2012 18:523-9.
Costa, M., Sturgeon, A., Arroyo, L., Kim, P., Allen-Vercoe, E., Staempfli, H. and Weese, J.S. Comparison of the Fecal Microbiota of Healthy Horses and Horses with Colitis by High Throughput Sequencing of the V3-V5 Region of the 16S rRNA Gene. PLoS One. 2012;7(7):e41484.
Allen-Vercoe, E., Reid G, Viner N, O’Doherty K, Lee C, Hota S, Gloor G, Kim P, Vanner S, Weese S, and Petrof EO, “A Canadian Working Group Report on Fecal Microbial Therapy: Microbial Ecosystems Therapeutics” Canadian Journal of Gastroenterology, in press.
Allen-Vercoe, E. as part of The Human Microbiome Project Consortium. “A framework for human microbiome research” Nature. 2012 Jun 13;486 (7402):215-21 .
Allen-Vercoe, E. as part of The Human Microbiome Project Consortium. “Structure, Function and Diversity of the Human Microbiome in an Adult Reference Population” Nature. 2012 Jun 13;486(7402):207-14.
Castellarin, M., Warren, R.L., Freeman, J.D., Dreolini, L., Krzywinsky, M., Strauss, J., Barnes R., Watson, P., Allen-Vercoe, E, Moore, R.A and Holt, R.A. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Research. 2012 Feb;22(2):299-306.
Allen-Vercoe, E., Strauss, J. & Chadee, K. Fusobacterium nucleatum – an emerging gut pathogen? Gut Microbes, 2011 Sep 1;2(5).
Dharmani P, Strauss J, Ambrose C, Allen-Vercoe E, Chadee K. Fusobacterium nucleatum Infection of Colonic Cells Stimulates MUC2 Mucin and Tumor Necrosis Factor Alpha. Infect Immun. 2011 Jul;79(7):2597-607.
Strauss, J., Kaplan, G., Beck, P.L., Panaccione, R., Rioux, K, DeVinney, R., Lynch, T. and Allen-Vercoe, E. Invasive potential of gut mucosa-derived Fusobacterium nucleatum positively correlates with IBD status of the host. Inflammatory Bowel Diseases, 2011 Sep;17(9):1971-8.
Allen-Vercoe, E, as part of the Human Microbiome Jumpstart Reference Strains Consortium (Nelson K.E. et al.) A catalog of reference genomes from the human microbiome. Science. 2010 May 21;328(5981):994-9.
Strauss J, White A, Ambrose C, McDonald J, Allen-Vercoe E. Phenotypic and genotypic analyses of clinical Fusobacterium nucleatum and Fusobacterium periodonticum isolates from the human gut. Anaerobe. 2008 Dec;14(6):301-9.
The Allen-Vercoe lab, Gutsy Walk for the CCFC, June 2012
Julie has been instrumental in developing the Roboguts as a model of the human distal gut microbial ecosystem. Her project aims to examine the role of the poorly-understood gut microbial biofilms in the maintenance of homeostasis during stress.
Co-supervised by Dr. Terry Van Raay, MCB, Mike is developing the zebrafish embryo model as an innovative system to study the effects of gut bacterial metabolites on development, including neurogenesis and behaviour. firstname.lastname@example.org
Co-supervised by Dr. Cezar Khursigara, MCB, Kathleen’s project is aimed at trying to identify the gut microbes that initiate biofilm formation within the gut, and how selected probiotic strains can influence this process. email@example.com
Kyla is investigating virulence factors of Fusobacterium nucleatum as well as trying to understand infectious synergies of F. nucleatum with other gut microbial species.
Ian is studying the human distal gut microbiota's response to different resistant starches derived from novel lines of maize.
Christian is using the Roboguts to model the RePOOPulate ecosystem and to define the microbial species within this ecosystem and others like it that promote ecosystem robustness and resilience, with a view to the use of such therapeutic ecosystems to treat C.difficile infection.
Erin is investigating the metabolic output of whole gut microbial communities cultured from autism spectrum disorder patients in the Roboguts, and assessing the effect that these metabolites may have on gut colonocytes in vitro.
M.Sc., Research Tech.
Michelle contributes her technical expertise to all of the projects within the lab, and also oversees the work to culture, characterize and archive novel bacterial species from the human gut, including preparation of genomic DNA for sequencing as part of the Human Microbiome Project.
Chris does all the things that keep the lab running smoothly, including animal work, purchasing, shipping and receiving paperwork, due diligence and maintenance & repair of equipment.
The URA student selected for a summer studentship in the lab this year is Sarah Thomson. Sarah will be characterizing a novel bacteriophage isolated from F.nucleatum, under the guidance of Kyla.
Congratulations to Jackie Strauss, Ph.D. September 2011! Jackie’s project was focused on understanding the role of the anaerobic pathogen, Fusobacterium nucleatum, in the etiology of IBD.