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Human Microbiome projects


Impact of maternal, diet and lifestyle factors on microbiome and its interactions with the host

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Human Microbiome projects


Impact of maternal, diet and lifestyle factors on microbiome and its interactions with the host

Amniotic Fluid Microbiome

Preterm birth. Preterm birth (PTB) is defined as birth before 37 completed weeks of gestation. It is the leading cause of neonatal and infant mortality. In Canada, 7.8% of babies are born preterm. This rate is close to 12% in United States. Of these babies, many face a lifetime disability. Very little is known about the causes and mechanisms of PTB. It is a multifactorial process resulting from interplay of factors, such as maternal genetics, infection, medical conditions, infertility treatments, and individual’s lifestyle including stress and excessive physical work, causing the uterus to change from quiescence to active contractions and to birth before term.

Infection and PTB. It is widely believed that intra-amniotic infection and inflammation has a major role in PTB. Studies showed that infections of the lower genital or gastrointestinal tract can directly or indirectly increase the chance of intrauterine infection and PTB. Thus, elicit the question whether or not PTB is an infectious disease! Also, it is not clear whether or not AF is a sterile environment! Historically, microbial culture of amniotic fluid (AF) has been recognized as the “gold standard” for the detection of intra-amniotic infection. However, uncultivable or difficult-to-cultivate bacteria will not be identified by culture. As a result, intra-amniotic inflammation is frequently detected in the absence of an infective agent. In this research, we are characterizing the microbial composition of the AF of women with and without PTB symptoms using MiSeq illumina sequencing in parallel with culturomics methods.

COLLABORATORS AND SPONSORS

Dr. Shadi Sepehri, Clinical Microbiologist, Children Hospital Research Institute of Manitoba; Dr. Savas Menticoglou, Maternal fetal medicine specialist, Womens Hospital, University of Manitoba; Dr. Vanessa Poliquin, Obstetrics and Gynecologist,  Fellow in Reproductive Infectious Diseases, University of Manitoba; Dr. Adam Burgener, Head of Proteomics, National HIV and Retrovirology Laboratory, Public Health Agency of Canada.

 

The Manitoba PERSONALIZE Lifestyle Research (TMPLR) program – 

GENETICS, LIFESTYLE, and MICROBIOME INTERACTIONS

The role of lifestyle factors, such as physical activity, nutrition, and sleep, in human health and disease is well established. These lifestyle factors are often targeted by prevention and treatment strategies to reduce chronic conditions, such as metabolic syndrome, diabetes, obesity and cardiovascular disease. However, how these modifiable lifestyle factors interact with newer determinants of health, such as gut microbiome and metabolic phenotype of the individual is relatively unknown. Both host genetics and environmental exposures throughout the life (such as method of birth, breastfeeding, diet, and medication use) can have life-long impact on gut microbiome. Gut microbiome on the other hand has been shown to impact host physiology, metabolism, and immune function and to confer indirect (immune-mediated) and direct resistance against enteric pathogens. Disruption of gut microbiome or dysbiosis – which is referred to an abnormal balance of beneficial and protective members of microbiota – has been linked to a growing number of chronic conditions such as obesity, insulin resistance and inflammatory bowel diseases. The dysbiosis of gut microbiome impacts the profile of microbially-drived metabolites and small molecules produced by the microbiota. These molecules influence the metabolic and immunological capacities of the host both within and outside of the gut, i.e. through enterohepatic pathway or gut-brain axis. Given the dynamics of the gut microbiome and metabolome, and their potentially causal roles in multiple chronic diseases, microbiome and metabolome profiles of individuals can be used as personalized biomarkers of health status, and thus, as targets for intervention.

During the phase I of this research program, we are conducting a cross-sectional investigation of the interaction between lifestyle, genetics, and gut microbiota and how these are associated with additional risk factors for chronic conditions prevalent in Manitobans, such as obesity, type 2 diabetes, metabolic syndrome, and cardiovascular disease.

COLLABORATORS AND SPONSORS

Senior project lead: Dr. Peter Jones, Junior project lead: Dr. Meghan Azad, Nutrition project lead: Dr. Heather BlewettPhysical activity project lead: Dr. Todd Duhamel, Sleep project lead: Dr. Diana McMillan, Genetics project lead: Dr. Peter Eck, Gut microbiome project lead: Dr. Ehsan Khafipour

Visit here for the full list of researchers.

 

Human Milk Microbiome 

Breast milk contains a variety of immune modulatory components, antimicrobial peptides, and nutrients as well as a collection of microbes, the composition of which alters in local pathologies of the breast, e.g. mastitis or mode of delivery. It is believed that milk microbiota helps in shaping the infant’s gut microbiota and is important in the child’s health. In collaboration with Dr. Meghan Azad, we have access to samples from Canadian Healthy Infant Longitudinal Development (CHILD) national birth cohort through which we characterize the compositional and functional capacity of human milk microbiome and its potential role in development of childhood obesity and asthma. 

Sponsors

 

diet and gut microbiome

BETA-GLUCAN; MONOUNSATURATED, POLYUNSATURATED AND SATURATED OILS AND FATS

Short- and long-term dietary intake of micro- and macronutrient highly impact the composition and functional capacity of gut microbiome and positively or negatively influence the risk factors for metabolic disorders and cardiovascular disease. Through several research projects, we are investigating the impact of dietary factors on gut microbiome and human health. We are also assessing  the effect of weaning strategies on development of the gut microbiome during the early stage of life.

Collaborators and Sponsors

Dr. Peter Jones, Human Nutritionist, University of Manitoba; Dr. Nancy Ames, Human Nutritionist, Agriculture and Agri-Food Canada and University of Manitoba; Dr. James Friel, Infant Nutritionist, University of Manitoba.

 

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Animal models of human diseases


Animal models of human diseases


Mouse and Pig models of inflammatory bowel disease

Ulcerative colitis (UC) and Crohn’s disease (CD) represent the two major forms of inflammatory bowel disease (IBD) that are characterized by alternating phases of clinical relapse and remission. Although these two diseases have some characteristics in common, important clinical differences exist. Ulcerative colitis causes ulceration and inflammation of the colon and rectal mucosa and presents with symptoms, such as rectal bleeding, frequent stools, mucus discharge from the rectum, tenesmus, and lower abdominal pain. Crohn’s disease, however, causes inflammation that extends into the deeper layers of the intestinal wall; it may affect any part of the digestive tract, and it presents with abdominal pain, weight loss, prolonged diarrhea with or without gross bleeding, fatigue, and fever. The etiology of both CD and UC is unclear; but accumulating data suggest that a genetic predisposition or a combination of genetic susceptibility factors, defective mucosal barrier, altered innate and adaptive immune responses and their interactions with commensal gut microbiota in the enteric environment, and different environmental factors contributes to the initiation and the recurrence of these diseases.
Much of the recent progress in the understanding of immunity has been achieved using experimental animal models of intestinal inflammation. Although these models do not represent the complexity of human disease and do not replace studies with patient samples, they are valuable tools for studying many important disease aspects that are difficult to address in humans and they, therefore, provide a platform through which some of the complex mechanisms can be systematically investigated. Most of these models require exogenous manipulation based either on chemical induction, immune cell transfer or gene targeting, and only a few models occur spontaneously without any exogenous manipulation. Chemically-induced models of intestinal inflammation are among the most commonly-used animal models of IBD as the onset of inflammation is immediate and the procedure is relatively straightforward. Even though they have limitations like all other models, they present some important immunological and histopathological aspects of IBD in humans.

We are using dextran sulphate sodium (DSS)-induced colitis, and 2,4 dinitrobenzenesulfonic acid  (DNBS)-induced colitis – the most widely used and characterized experimental model of UC and CD, respectively – to induce colitis in mice. However, because pigs share a similar gastrointestinal morphology and physiology with humans, they are more suitable model for studying IBD. We have developed a pig model using carrageenan gum, a sulphated polysaccharide, to chemically induce intestinal ulceration and inflammation similar to UC. In this line of research, we are constantly improving our animal models, and use them for understanding the etiology of IBD or evaluation of different prevention and treatment strategies. We are also using DSS and DNBS models for testing the impact of maternal factors on development, stability and resilience of gut microbiome in the offsprings. 

Collaborators and Sponsors

Dr. Jean-Eric Ghia, Immunologist, University of Manitoba, and Inflammatory Bowel Disease Clinical and Research Centre; Dr. Charles Bernstein, Gastroenterologist, University of Manitoba, and Inflammatory Bowel Disease Clinical and Research Centre; Dr. Charles Elson, MD and Microbiologist, University of Alabama at Birmingham.

 

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Ruminant microbiome projects


Ruminant microbiome projects


Rumen Microbiome in health and Disease

The bovine rumen is a classical host-microbe symbiotic system, and disturbances in this exquisitely balanced ecosystem leads to disease in the host. In my research I'm working with a range of disorders that are linked to dysbiosis of rumen microbiome, including acidosis and subacutre ruminal acidosis, bloat, milk fat depressions. My research focus is on both understanding the etiology of these disorders as well as development of prevention and treatment strategies for stabilizing the rumen environment. Development of rumen microbiome at early stage of life, and manipulation of rumen environment to reduce methane emission from cattle are additional components of my collaborative research program.

Collaborators and Sponsors

Dr. Jan Plaizier, Ruminant Nutrition, Gut Health, University of Manitoba; Dr Greg Penner, Ruminant Nutrition, Gut Health, University of Saskatchewan; Dr. Mike Steele, Ruminant Nutrition, Gut Health, Nutrigenomics, University of Alberta; Dr. Juan Loor, Nutriphysiogenmics, University of Illinois; Dr Tim McAllister, Rumen Microbiology, Agriculture and Agri-Food Canada at Lethbridge; Dr. Robert Forster, Rumen Microbiology, Agriculture and Agri-Food Canada at Lethbridge; Dr. Surya Acharya, Forage Breeder, Agriculture and Agri-Food Canada at Lethbridge; Dr. Kevin Harvatine, Nutritional Physiology, Penn State University; Dr. Pia Anderson, Large Animal Surgery, Metabolic Disorders, Swedish University of Agricultural Sciences; Dr. Annemette Danscher, Metabolic Disorders, University of Copenhagen; Dr. Brian Amiro, Soil Science, Greenhouse Gases, University of Manitoba; Dr. Chaouki Benchaar, Dairy Nutrition, Agriculture and Agri-Food Canada at Sherbrooke; Dr. Kim Ominski, Beef Cattle Nutrition, Dr. Ali Assadi-Alamouti, Nutritional Physiology, University of Tehran.

 
 

 

Vaginal microbiome and development of rumen and hindgut microbiota in calves

Nutritional and physiological stressors are one of the significant underpinnings of the gut-brain-microbiome axis. Exposure to these stressors alters the brain response and results in disturbed hormonal profile that on one hand affects the diversity and behavior of the gastrointestinal and vaginal microbiomes, and on the other hand prevents conception, proper implantation and subsequent maintenance of the newly conceived embryo. A healthy vaginal microbiome has a key role in improving reproductive performance and preventing infectious diseases through several mechanisms, such as competitive exclusion of pathogenic microorganisms, stimulation of the host immune system, and production of antimicrobial compounds. On the other hand, the vaginal microbiome has a key role in the initial colonization of the gut in newly born calves. Although the first colonizers are not the best colonizers, their composition and diversity influence the pattern of secondary colonizers in the gut. The later, can have a major impact on lifelong stability of the gut microbiome and gut health in individual animals, and thus, may shape their susceptibility to different metabolic disorders and infectious diseases throughout life.  This is an important component of my research program and several research is currently ongoing in my group.

Collaborators and Sponsors

Dr. Jan Plaizier, Ruminant Nutrition, Gut Health, University of Manitoba; Dr. Juan Loor, Nutriphysiogenmics, University of Illinois

 

 

Featured videos by Dairyexnet

 

 

Mammary MICROBIOME AND mastitis

Mastitis, also known as intramammary infection (IMI), is the most costly disease to the dairy industry. Decreased milk yield, lower milk quality, higher treatment costs and premature culling of chronically infected cows are major economic losses related to mastitis. In the bovine mammary glands, infections occur mostly upon transgression of bacteria past the teat canal. Clinical mastitis is characterized by alterations in milk composition and appearance; decreased milk production; elevated body temperature; and swelling, redness, or heat in infected quarters. However, subclinical mastitis in dairy herds is more important because this form is (a) 15 to 40 times more prevalent than the clinical form, (b) it usually precedes the clinical form, (c) it is of long duration, (d) it is difficult to detect, (e) It reduces milk production, and (f) it adversely affects milk quality. Cows from well-managed dairy herds utilizing the most recent and effective control measures can experience a high rate of mastitis, especially during the first 90 d of lactation. Risk factors associated with resistance/susceptibility to mastitis include management practices such as nutrition, housing, milking machine factors, and pre- and post-milking teat disinfection, and cow factors including parity, lactation stage, teat-end hyperkeratosis, and SCC. 

My research group determines the temporal dynamics in the microbiome profile of milk during lactation and investigates if the microbiome profile of the mammary gland is deterministic of udder health. 

Collaborators and Sponsors

Dr. Jan Plaizier, Ruminant Nutrition, Gut Health, University of Manitoba; Dr. Herman Barkema, Epidemiology and Immunology of Infectious Diseases, University of Calgary, Dr. Jeroen De Buck, Bacteriology and Infectious Diseases, University of Calgary.

 

Mastitis From Start to Finish

Featured Videos by DAIReXNet

 
 
 
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Swine microbiome projects


Swine microbiome projects


Vaginal microbiome,

neonatal and post-weaning diarrhea,

GUT MICROBIOME Development, and

Alternative to antibiotics

The increase in antibiotic-resistant bacteria and spread of such resistance to other microorganisms in the environment has put pressure on livestock production systems to find alternatives for sub-therapeutic use of antibiotics in animals’ diet. In collaboration with my colleagues at Universities of Manitoba, Saskatchewan and Guelph, I am assessing the effect of antibiotic alternatives on health and productivity of young pigs. Our research shows that intensity of E. coli K88 infection in young pigs depends on the diet, environmental stressors and the profile of gut microbiome.

 Also, through an independent research, I’m investigating the role of sow’s vaginal and gut microbiomes on neonatal diarrhea and development of piglets gut microbiome with the goal of developing new probiotic targets that can be administered in-feed or intra-vaginally. As such, a better understanding of microbiome composition and function improves our ability to design optimal solutions for disease prevention in young pigs. 

Collaborators and Sponsors

Dr. Martin Nyachoti, Swine Nutrition, Gut Health, University of Manitoba; Dr. Andrew Van Kassel, Swine Nutritional Physiology, Microbiology Ecology, University of Saskatchewan; Dr. Kees de Lange, Swine Nutrition, University of Guelph; Dr. Elijah Kiarie, Swine Nutrition, Gut Health, University of Guelph; Dr. Woo Kyun Kim, Swine Nutrition and Molecular Biology.

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Environmental Research


Environmental Research


PORCINE EPIDEMIC DIARRHEA VIRUS (PEDV)

In recent years, porcine epidemic diarrhea virus (PEDv) has been a major challenge for the North American swine industry, killing more than 8 million pigs since Feb 2013. Despite the extensive effort of various Canadian pork producer and several other organizations in increasing the biosecurity level of farms, several Canadian swine farms were identified to be PEDv positive and faced recurrent infections. Eradication of PEDv from the positive sites, if not impossible, is a major challenge. In Manitoba, 5 positive cases (a case can be a recurrent outbreak in a farm that was previously identified to be PEDv positive) have been reported to this date. Handling and management of the infected manure is a major challenge for PEDv eradication. As Manitoba swine farms generally store their manure in open lagoon systems and the ambient temperature of outdoor storages are lower than under barn storages (especially under Manitoba’s climate), the survivability of PEDv in such lagoons may be high. Despite best efforts, not much is known about PEDv survivability and infectivity within open lagoons over a marked period of time. In this project, we examined the survivability and infectivity of PEDv in two on-farm lagoons. We also tested the survivability of PEDv at different temperatures and the effects of chlorination and new disinfectent methods on PEDv survivability and infectivity under experimental settings.

Collaborators and Sponsors

Prairie Agricultural Machinery InstituteExigence Technologies.

 

 

CReate H2o

The CREATE H2O program for First Nations water and sanitation security is designed to address research science and training gaps that are preventing effective, culturally appropriate investments in water and sanitation security on First Nations reserves. It is the first science-engineering research training program in Canada that combines technical water and wastewater management training with Indigenous theory, law and methodological skills training. My team incorporates a range of DNA- and RNA-based methodologies for environmental microbial surveys and water born pathogen source tracking.

Collaborators and Sponsors

Dr. Annemieke Farenhorst, Program Lead, Soil Science, University of Manitoba; Dr. Ayush Kumar, Microbiology, University of Manitoba; Dr. Dilantha Fernando, Plant Science, University of Manitoba.

 

 

Compost Tea

Compost, and more recently its extraction products, have been known to provide noticeable advantages to plants when applied to its growth medium. The extremely varied and abundant microbial communities present in compost products are thought to provide the varied benefits to crops, such as increased yield, systemic resistance to pathogens and stressors, direct competition with pathogens for limiting nutrients, direct role in supplying nitrogen to the plant, inducing proliferation of root growth, and the production of phyto-hormones, to name a few. Identifying the communities responsible for these functions can provide insight into compost formulation, and how to gain the appropriate benefits dependent on specific crop needs.

Collaborators and Sponsors

Overton Environmental Inc.