个人简介
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 microbiota and its influence on human health and disease, a program that I brought with me to Guelph in December 2007.
My motto: "My microbes told me to do it"
My hobbies: Gardening, reading, reading about gardening
Education
B.Sc. (Hons) Biochemistry, University of London
Ph.D. Molecular Biology, Open University in conjunction with CAMR, UK Post-doctoral fellow, University of Calgary
研究领域
Research in my laboratory is focused on the study of the normal human gut microbiota, 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 microbiota 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 microbiota 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. HOW DOES THE GUT MICROBIOTA RESPOND TO ITS ENVIRONMENT?
We are interested in the metabolic output of the gut microbiota and how this changes in response to environmental stimuli. We are involved in an ongoing project in collaboration with Agriculture and Agri-Food Canada to determine how the colonic microbiota derived from different individuals responds to dietary substrates derived from pulses that are processed in different ways, with a view to understanding how diet may be tailored to microbiota types to enhance health. We are also interested in the response of the gut microbiota to drugs, food additives, and host proteins. Together with the Aucoin lab, University of Waterloo, we are exploring proton NMR as a tool for shotgun metabolomics of microbial ecosystems to help us understand metabolic shifts in response to microbiota perturbation. We currently apply this approach to the study of several diseases, including IBD, regressive autism, and most recently, neonatal necrotizing enterocolitis (NEC).
3. WHICH BACTERIAL SPECIES OF THE NORMAL MICROBIOTA CAN CONTRIBUTE
TO DISEASE?
In a healthy person, despite the constantly changing environment within the gut, the resident microbiota 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 several key diseases with connections to the gut microbiota: IBD, regressive (late-onset) autism, recurrent (refractive) Clostridioides difficile infection (CDI), colorectal cancer, diabetes and NEC.
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 microbiota. A large part of the research in our lab is focused on determining which species, or groups of species, of the gut microbiota 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 microbiota 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 microbiota 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 microbiota 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. Recently, Dr. Allen-Vercoe co-founded a spin-off company, Nubiyota, to help pursue “Microbial Ecosystem Therapeutics” as an emerging new paradigm in medicine.
Click on this link to download a Medical Post article describing this work.
Click on this link to view a 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.
Diabetes is a serious metabolic disease where the body has difficulty in regulating blood sugar levels. There are 2 main forms: type-1 (T1D), resulting from the pancreas producing insufficient amounts of insulin; and type-2 (T2D), resulting from a lack of response to insulin by the body’s cells. There is a growing amount of evidence that the gut microbiota plays a role in the development of both conditions. In T1D, exposure to certain microbial species found in the gut may trigger an autoimmune response to the insulin-producing cells of the pancreas in susceptible individuals. In T2D, damage to the gut microbiota may result in an ecosystem that is metabolically imbalanced, in turn affecting metabolism of the whole body. Our lab is working in conjunction with the lab of Jayne Danska, Sick Kids, to try to understand how, and which, gut microbes contribute to diabetes.
NEC is a serious disease that is particularly prevalent in preterm babies and has high morbidity and mortality rates. While we know that NEC is a disease that is directly related to the gut microbiota, what we don't yet understand is how the microbiota triggers NEC in some infants but not others, even when the same sorts of microbes are present in the gut. We are working in collaboration with researchers at the University of Chicago to try to understand how functional changes in the gut microbiota from preterm babies, perhaps influenced by the medical interventions that premature infants require, might trigger disease.
The gut microbiota of livestock animals
The lab's work has so far been focused on the human gut microbiota (the collection of microbes in the gut), and its importance to our wellbeing. However, a long, hard look at the methods through which animals are intensively reared for food production has led Dr. A-V to start to consider how modern interventions in animal husbandry might damage the gut microbes, and hence the health, of farm animals. What is clear, for both humans and animals, is that modern living has eroded the microbial diversity of the gut, and this lack of diversity may underlie a whole range of different diseases. We are turning our attention to the gut microbiota of pigs as our first foray into veterinary microbiota research. In pigs, a lack of gut microbiota diversity may contribute to infection, failure to thrive, and other health problems that currently plague pork producers.
What if we could replace the missing microbes and by doing so, restore health to farmed animals? We are working to create a healthy gut microbial ecosystem for pigs - kind of like a 'super-probiotic' that contains the microbes that intensively reared animals might be missing. For this project we are working with the de Martines family of Perth Pork Products, near Stratford Ontario, who raise a herd of wild boar in a close-to-natural setting; understanding the diversity contained within these animal guts is a first step to understanding how we might be able to improve gut health in intensively reared animals.
近期论文
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Murall C.L., Abbate J.L., Puelma, Touzel M., Allen-Vercoe E., Alizon S. Froissart R., McCann K., (2017) Invasions of host-associated microbiome networks. Advances in Ecological Research in press.
Moniz, K., Ropers, M.-H., Dudefoi, W., Allen-Vercoe E., Walker, V. (2017) Impact of food grade and nanoTiO2 particles on a human intestinal community Food and Chemical Toxicology, in press.
Belik, J., Shifrin, Y., Bottiglieri, T., Pan, J., *Daigneault, M., Allen-Vercoe, E. (2017) Intestinal microbiota as a tetrahydrobiopterin exogenous source in hph-1 mice. Scientific Reports, in press.
Yen, S., Bolte, E., Aucoin, M. and Allen-Vercoe, E. (2017) Metabolomic evaluation of fecal water preparation methods: the effects of ultracentrifugation. Current Metabolomics, in press.
Carlucci C, Petrof EO, Allen-Vercoe E. (2016) Fecal Microbiota-based Therapeutics for Recurrent Clostridium difficile Infection, Ulcerative Colitis and Obesity. EBioMedicine. Nov;13:37-45.
Martz, S., He, S., Noordhof, C., Hurlbut, D. J., Gloor, G. B., Carlucci, C., Weese, J.S., Allen-Vercoe, E. Sun, J., Claud, E.C. Petrof, E.O. 2016. A human gut ecosystem protects against C. difficile disease by targeting TcdA. Journal of Gastroenterology (in press).
Munoz S, Guzman-Rodriguez M, Sun J, Zhang YG, Noordhof C, He SM, Allen-Vercoe E, Claud EC, Petrof EO. Rebooting the microbiome. Gut Microbes. 2016 13:1-11.
Wissenbach DK, Oliphant K, Rolle-Kampczyk U, Yen S, Höke H, Baumann S, Haange SB, Verdu EF, Allen-Vercoe E, von Bergen M. Optimization of metabolomics of defined in vitro gut microbial ecosystems. Int J Med Microbiol. 2016 (in press).
Gupta, S., Allen-Vercoe, E., & Petrof, E. Fecal transplantation-in perspective.Therapeutic Advances in Gastroenterology 2015 9L229-39.
Allen-Vercoe, E. & Petrof, E.O. Using bugs as drugs: Microbial ecosystem therapeutics. Canada Communicable Disease Report 2015 (in press).
Santiago-Rodriguez, T. M., Ly, M., Daigneault, M., Brown, I. H., McDonald, J. A., Bonilla, N., Allen-Vercoe, E., Pride, D., (2015). Human fecal cultures support diverse phage communities. Microbiome 2015 (in press).
Cochrane K, McGuire AM, Priest ME, Abouelleil A, Cerqueira GC, Lo R, Earl AM, Allen-Vercoe E. Complete Genome Sequences and Analysis of the Fusobacterium nucleatum subspecies animalis 7-1 Bacteriophage φ Funu1 and φ Funu2. Anaerobe. 2016 38:125-9.
Martz SL, McDonald JA, Sun J, Zhang YG, Gloor GB, Noordhof C, He SM, Gerbaba TK, Blennerhassett M, Hurlbut DJ, Allen-Vercoe E, Claud EC, Petrof EO. Administration of defined microbiota is protective in a murine Salmonella infection model. Sci Rep. 2015 5:16094. doi: 10.1038/srep16094.
Costa MC, Stämpfli HR, Allen-Vercoe E, Weese JS. Development of the faecal microbiota in foals. Equine Vet J. 2015 (in press)
Jumas-Bilak E, Bouvet P, Allen-Vercoe E, Aujoulat F, Lawson PA, Jean-Pierre H, Marchandin H. Rarimicrobium hominis gen. nov., sp. nov., the fifth genus in the phylum Synergistetes that includes human clinical isolates. Int J Syst Evol Microbiol. 2015 (in press)
Natividad JM, Pinto-Sanchez MI, Galipeau HJ, Jury J, Jordana M, Reinisch W, Collins SM, Bercik P, Surette MG, Allen-Vercoe E, Verdu EF. Ecobiotherapy Rich in Firmicutes Decreases Susceptibility to Colitis in a Humanized Gnotobiotic Mouse Model. Inflamm Bowel Dis. 2015 8:1883-93.
Frye RE, Slattery J, MacFabe DF, Allen-Vercoe E, Parker W, Rodakis J, Adams JB, Krajmalnik-Brown R, Bolte E, Kahler S, Jennings J, James J, Cerniglia CE, Midtvedt T. Approaches to studying and manipulating the enteric microbiome to improve autism symptoms. Microb Ecol Health Dis. 2015 26:26878.
Yen S, McDonald JA, Schroeter K, Oliphant K, Sokolenko S, Blondeel EJ, Allen-Vercoe E, Aucoin MG. Metabolomic analysis of human fecal microbiota: a comparison of feces-derived communities and defined mixed communities. J Proteome Res. 2015 14(3):1472-82.
Das, P., McDonald, J., Petrof, E., Allen-Vercoe, E., & Walker, V. Nanosilver-mediated change in human intestinal microbiota. Journal of Nanomedicine & Nanotechnology. 2014 5:5.
Costa, M., Stämpfli, H., Arroyo, L., Allen-Vercoe, E., Gomes, R., Weese, J.S. Changes in the Equine Fecal Microbiota Associated with the Use of Systemic Antimicrobial Drugs. BMC Veterinary Research. 2015 11:19.
Allen-Vercoe, E. & Toh, M. The Human Gut Microbiota with reference to Autism Spectrum Disorder: considering the whole as more than a sum of its parts. Microbial Ecology in Health & Disease. 2015 Jan; 26:26309.
McDonald JA, Fuentes S, Schroeter K, Heikamp-deJong I, Khursigara CM, de Vos WM, Allen-Vercoe E. Simulating distal gut mucosal and luminal communities using packed-column biofilm reactors and an in vitro chemostat model. Microbiol Methods. 2015 Jan;108:36-44.
Allen-Vercoe E. Fusobacterium varium in Ulcerative Colitis: Is It Population-Based? Dig Dis Sci. 2015 Jan; 60(1):7-8.
Manson McGuire A, Cochrane K, Griggs AD, Haas BJ, Abeel T, Zeng Q, Nice JB, MacDonald H, Birren BW, Berger BW, Allen-Vercoe E, Earl AM. Evolution of invasion in a diverse set of Fusobacterium species. MBio. 2014 Nov 4;5(6):e01864.
Allen-Vercoe, E. & Jobin, C. Fusobacterium and Enterobacteriaceae: important players for CRC? Immunology Letters Dec;162(2PA):54-61.
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