Exploring the Microbiome

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Exploring the Microbiome Dr. Charu Kaushic Scientific Director, Institute of Infection & Immunity, Canadian Institutes of Health Research

What Is the Microbiome, Why Do We Care, and What’s the Importance of Microbiome Research?

If you’ve ever stopped at the refrigerated health food section of your grocery store, you would have seen a wide selection of products like pre- and probiotics. Television commercials tout the benefits of these products on your gut health and microbiota. But what exactly is the microbiota, how is it different from the microbiome, and why do we need to learn more about it through research?

H Dr. Puja Bagri

umans have an estimated 100 t rillion m ic r o b e s s uch a s vir uses, f ungi a nd parasites, but the most predominant microbe living on and within our bodies are the bacteria.

Together, these bacteria help form the human microbiota, and the genome of all the bacteria which live within our bodies help form the human microbiome — however, these terms are often used interchangeably. While a large majority of these bacteria reside in the gut, our skin, mouth, lungs, and reproductive and urinary tracts also have distinct microbiotas. Similar to fingerprints, each individual has unique communities of microbiota that are distinct for each person.

The relationship between humans and their microbiome is dynamic and complex. The microbiome begins to develop at birth as the baby passes through the vaginal canal and subsequently through breast milk, and it

changes quickly in the early years following exposure to new environmental factors. While it does somewhat stabilize after this point, the microbiome can fluctuate throughout life depending on diet, health, exercise, hormonal balance, and environmental exposures.

Many of the bacteria found within the microbiome exist in symbiosis with humans, meaning there is some benefit to both humans and the bacteria.

Conversely, there are also pathogenic bacteria that can cause potential harm.

Typically, in a healthy state, both symbiotic and pathogenic bacteria co-exist without any concern. However, a disturbance in this fine balance, also known as dysbiosis, can result in disease or illness.

The discovery of this hidden world of bacteria that lives within us and our increased understanding of how they influence our health is arguably one of the most exciting developments in health research in the last two decades.

For instance, we now know that a per-

son’s microbiome may influence their susceptibility to certain infections and contribute to illnesses such as diabetes, Crohn’s disease, Alzheimer’s, obesity, and anxiety. This is because the microbiome plays a key role in a diverse range of vital processes, including programming the immune system, controlling inflammation, defending against pathogens, providing nutrients to cells, facilitating metabolism, synthesizing vitamins, and even influencing behaviour by indirectly modulating the central nervous system.

We’re only beginning to understand the widespread impacts of the microbiome. The next phase of research will be exciting as we start to understand why and how different bacteria differentially affect our bodies and how we can manipulate the microbiome to improve human health.

Read more about the CIHR Canadian Microbiome Initiative at innovatingcanada.ca.

Publisher: Natalie Jacome Business Development Manager: Chelsea Siemon Country Manager: Nina Theodorlis Content and Production Manager: Raymond Fan Designers: Lauren Livingston, Filip Jansky Web Editor: Karthik Talwar All images are from Getty Images unless otherwise credited. This section was created by Mediaplanet and did not involve Toronto Star or its editorial departments. Send all inquiries to ca.editorial@mediaplanet.com.

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Leading the way in microbiome research The International Microbiome Centre at the University of Calgary is a translational research centre, designed to investigate the microbiome of humans, animals and the physical environment. Together, world class microbiome researchers, advanced technologies and relationship building will spark groundbreaking discoveries that harness the healing power of the microbiome.

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INTERNATIONAL MICROBIOME CENTRE (IMC)

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Dragana SkokovicSunjic Clinical Pharmacist & Author, Clinical Guide to Probiotic Products

The Science Speaks for Itself: Exciting Relief Options for Children’s Eczema When atopic dermatitis causes our babies and children to suffer from itchy, dry, and inflamed skin, probiotics are providing a new option for scientificallydemonstrated relief.

D.F. McCourt

W

hen we talk about the human microbiome, the first thing that comes to mind is usually the gut.

But, while the microorganisms in our digestive tract are indeed essential to good health, they’re far from the only microscopic friends in, or on, our bodies. Our skin itself is home to hundreds of species of symbiotic bacteria and fungi.

Understanding our relationship with them is critical to dermatological health, including the relief of skin conditions like atopic dermatitis.

The skin microbiome, the gut microbiome, and the other microbiota throughout our bodies aren’t isolated from one another.

No bacterial colony is an island, so to speak.

Recent scientific investigation has made it quite clear that interventions at the level of the gut can profoundly influence microbiome behaviour throughout the body, opening up significant new support pathways involving oral probiotics.

“In recent years, it has been established that there’s a relationship between the gut microbiome and skin health,” says clinical pharmacist Dragana Skokovic-Sunjic, author of the Clinical Guide to Probiotic Products published by the Alliance for Education on Probiotics. “New evidence is pointing to a gut-microbiome-skin relationship where bacteria are communicating via our immune responses to have effects on the skin. It’s believed that our gut microbiome can affect maturation of the immune system through this kind of a crosstalk.”

Expanding the treatment playbook for a common ailment For atopic dermatitis, specifically, the possibility of a new relief option through oral probiotics is highly welcomed. Atopic dermatitis, or eczema as it’s commonly known, is an extremely common and chronic inflammatory skin disease that can vary in intensity from inconvenient to overwhelming.

“Atopic dermatitis isn’t life-threatening, but it has a high impact on quality of life for those affected, especially kids,” says Skokovic-Sunjic.

“There’s intense itching, inflammation of the skin, disrupted skin barrier and risk of infection, interrupted sleep, and, when we’re not talking about infants, embarrassment related to the skin’s appearance. And atopic dermatitis is very prevalent in kids.

The statistics show that 20 percent of the infant population around the world has childhood eczema, and we see this prevalence increasing. We see it most often before five years of age, and it’s particularly frequent in very young infants.”

For decades, the standard eczema treatment has been topical corticosteroids, with systemic treatment being reserved for only the most severe cases due to the risk of unwanted side effects. For children, and especially infants, there’s limited data on the long-term effects of corticosteroid use, so health care providers are cautious about administering them. This leaves a void in treatment of juvenile atopic dermatitis, leaving parents with few choices backed by scientific evidence. Fortunately, with the advent of new clinical research, that gap is

finally being bridged and probiotic options are now available as an adjunctive therapy in combination with corticosteroids.

“A few single probiotic strains and combinations of strains have been explored and have shown benefits for atopic dermatitis,” says Skokovic-Sunjic. “One particular combination of three strains has shown improvement in kids 4 to 17 years of age when assessing symptoms with a specific index that includes objective and subjective measures. Across the board, there was significant improvement in symptoms with this combination of strains. This probiotic is taken by mouth, meaning that the bacteria first goes to the gut, modulates the gut response, and communicates with the immune system, which then promotes improvement in the skin condition.”

Hard science, over the counter The specific study that Skokovic-Sunjic is referring to was published in 2018 in the American Medical Association’s peer-reviewed journal JAMA Dermatology — the first time a probiotic study has been included in the prestigious publication. It’s important to recognize that, though probiotics are an overthe-counter option for relief, the supporting evidence is straightforward clinical research, held to the highest scientific standards. “This study uses selection criteria, includes randomization and blinding. There’s a group that receives placebo, and sometimes there will be crossover,” says Skokovic-Sunjic. “All those fancy words describe the gold standard of clinical investigation: a double-blind, placebo-controlled, randomized clinical trial.”

With that gold standard comes another important benefit — peace of mind. Many Canadians are rightly concerned about the safety of over-the-counter health products, but the scientific rigor with which probiotics are being investigated should thoroughly allay that concern. “People are often concerned about the safety of giving live bacteria to small kids, but there have been numerous studies showing their safety for use in children, infants, and even premature babies,” says Skokovic-Sunjic. “The only issue is selecting the appropriate one for the condition you wish to improve.”

We need to think about probiotics as a new opportunity to support skin health.

Asking which specific probiotic strains have scientific evidence, demonstrating effectiveness, and providing relief will help in the battle against skin conditions such as atopic dermatitis. Just as you wouldn’t take an antacid to deal with an ear infection, there’s no point in taking a Lactobacillus strain for a condition where only Escherichia has been shown to be effective. For atopic dermatitis, as for any condition, it’s essential that you speak with your doctor or pharmacist about the hard evidence when deciding which probiotic to use, or whether to use a probiotic at all.

Talk to your health care provider about probiotic options for atopic dermatitis and expand your own knowledge about the scientific basis of probiotic support at probioticchart.ca.

This page was sponsored by Volō Healthcare.

The Benefits of ProZema ProZema is a probiotic supplement in powder form that’s proven to reduce the symptoms of atopic dermatitis.

Key benefits include:

Eliminates the need for continued corticosteroids after 6 weeks of regular treatement

Significantly reduces SCORAD index values, which measure the severity of atopic dermatitis.

Improves diversity of the gut microbiome for healthy skin from the inside out

Can be taken just once daily and mixes easily with liquids and foods to fit into mealtime routines

ProZema is now available at a pharmacy near you.

Visit prozema.ca or scan the QR code to learn more.

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Dr. Kathy McCoy Professor in the Department of Physiology & Pharmacology, & Member, Snyder Institute, Cumming School of Medicine at the University of Calgary

Dr. Paul Kubes Professor in the Department of Physiology & Pharmacology, & Member, Snyder Institute, Cumming School of Medicine at the University of Calgary

The Microbiome Holds a Key to Human and Environmental Health The International Microbiome Centre at the University of Calgary is a world leading research centre for studying the microbiome of humans, animals, plants, and the physical environment.

O Abigail Cukier

ur bodies are home to trillions of microbes, including bacteria, fungi, and viruses, collectively known as the microbiome. Found on all mucosal and barrier surfaces, with the largest numbers in the small and large intestines, these microbes have a huge impact on our health. For example, the microbes in our gut train the immune system, break down potentially toxic food compounds, and synthesize vitamins.

Each person develops their own mix of microbes, determined by genetics and factors such as diet, previous infections, and environmental exposure.

These can either be beneficial or put us at greater risk for disease. Disturbances to the microbiome have been linked with diseases such as inflammatory bowel disease, type 1 diabetes, metabolic diseases, obesity, cancer, anxiety, and depression.

And it’s not just humans who have a microbiome — animals, plants, soils, and oceans have them, too. While scientists are still in the early stages of fully understanding the microbiome, there has been an explosion of exciting research in this area, and the International Microbiome Centre at the University of Calgary is a leader in the field.

World-class researchers and advanced technologies Founded in 2015, the International Microbiome Centre (IMC) is a translational research centre designed to investigate the microbiome of humans, plants, animals, and the physical environment. World-class microbiome researchers are using advanced technologies to make important discoveries that will harness the healing power of the microbiome. One of those researchers is Dr. Kathy McCoy, a professor in the Department of Physiology and Pharmacology and a member of the Snyder Institute at the University of Calgary.

Dr. McCoy is studying interactions of the gut microbiome with the immune system, including how a mother’s microbiome plays a role in shaping a baby’s immune system.

“There’s a critical window in early life, when the immune system is very open to receiving signals from the microbiome. We believe that alterations during this critical period have an impact on the health of the child, in terms of increased susceptibility, especially to immune-mediated diseases like asthma, dermatitis, and food allergies, autoimmune diseases like type 1 diabetes, and even neurodevelopmental disorders, such as autism spectrum disorder,” says Dr. McCoy. Dr. McCoy is also studying how interactions between the microbiome and the immune system can modulate the effectiveness of certain treatments, such as cancer therapy. In one recent study, Dr. McCoy and colleagues found that three bacterial species significantly

enhanced the efficacy of immunotherapy in cancer treatment in mice.

This approach also allows researchers to pool their resources to be able to use the most advanced technologies, Potential to treat disease says Dr. Shaunna Huston, Director of “What I think is most exciting is that we Programs and Business at the IMC. can harness the power of the microbiFor example, the centre’s bioinformome to treat disease,” says Dr. McCoy. atics platform analyzes big data from “We can’t change our genes, but we can multiple sources (including genomics, imaging, metabolomics, clinical and modify our microbiome. And the more that we understand this communimore) to answer research questions. cation between the microbiome and Its genomics platform can assess which the immune system, in which differmicrobes are present and identify ent microbial species are beneficial, immune cell changes in response to the the greater our odds are of hopefully microbiome. This will help us underdesigning microbial therapies that can stand the effect of the microbiome on humans, animal health, agriculture, treat disease.”

Dr. Paul Kubes is another IMC energy, and the environment. Its germresearcher. He heads the University of free facility, which is one of the largest Calgary’s major research strategy for academic facilities worldwide, allows Infections, Inflammation, and Chronic researchers to study mice that have no Diseases in the Changing Environment. microbes in or on them. “Then we can Dr. Kubes is using advanced technoladd back single microbes or a communogy to watch the immune system at ity of microbes to study the immune work. His lab is imaging the organs in system response to specific microbes a living species to understand what the and their relationship to chronic disimmune system is doing during variease,” says Dr. Huston. ous diseases. “We’re looking at what The IMC also contributes to happens to immune cells and how they IMPACTT, the cross-disciplinary Canfunction and what the role of the microadian Microbiome Research Centre biome is and its effect,” he says. funded by the Canadian Institutes of Dr. Kubes says it’s important to Health Research, to strengthen Canada’s remember that the microbiome links position as an international leader in us all. “If the grass at a farm is sprayed microbiome research. The IMPACTT with a substance and the cows get research team, including University of Calgary researchers Drs. Paul Kubes, into it, their microbiome is altered and they develop disJoe Harrison, Braedon ease or have certain McDonald, Ian Lewis, pathogens. If that food Ma rk us G eu k ing, enters the human food Kathy McCoy, MarieA major focus is to chain, it can be a huge Claire Arrieta, and build collaborations problem,” he says. “I Laura Sycuro, plus researchers from across think understanding and partnerships, the microbiome, not working with clinicians, Ca nada, including just from the perspecindustry, government, Drs. Fiona Brinkman, tive of humans, but also C el i a Gr e enwo o d , and other universities from the perspective of William Hsiao, Jayne to move microbiome what we eat — and what Danska, Anita Kozyrresearch forward. Our eats those things — is skyj, Philippe Gros, vision is to harness the absolutely critical.”

Karen Madsen, and power of the microbiDr. McCoy agrees.

Diego Silva, provides ome for better living, “We live in a very conto promote health and a network of expertise nected world, so we to researchers across treat disease.

Canada, develops tools can’t have a narrow view,” she says. “We need to realize that to strengthen microbiome research, and the microbiome affects everything. It’s fosters collaboration between researchnot just a human issue.” Dr. McCoy says ers. The IMC also recently received a that it’s important to understand the Canadian Foundation for Innovation One Health perspective, which recoggrant to build the Wild Microbiome and nizes that the health of people is closely Immunity Centre, in which researchers connected to the health of animals and will study the microbiome and immunthe environment. obiome of wild mice, which are much closer to those of humans. This will Multidisciplinary approach help researchers come much closer to improves research establishing therapeutics that would This is one of the reasons that the IMC work in humans. takes a multidisciplinary approach, “The vision of the IMC was to take for example, studying the use of proresearch and be able to put it into biotics to prevent infections in hospital practice,” says Dr. Huston. “A major patients, exploring oil sands for microbfocus is to build collaborations and ial compounds that could combat partnerships, working with clininfection, manipulating the microbiicians, industry, government, and ome in livestock to treat diseases such other universities to move microbias mastitis, and understanding the ome research forward. Our vision is to wild or natural microbiome in animals harness the power of the microbiome (mice) to expediate the translation of for better living, to promote health research into practice. and treat disease.”

Dr. Shaunna Huston Director of Programs & Business, IMC, Department of Physiology & Pharmacology, Cumming School of Medicine, University of Calgary

This page was sponsored by the University of Calgary.

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Dr. Michael Surette Professor of Medicine, McMaster University

Dr. Premysl Bercik Professor of Medicine, McMaster University

Dr. Stephen Collins Director, Farncombe Family Digestive Health Research Institute & Professor of Medicine, McMaster University

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Studying How to Improve Health

by Reshaping the Gut Microbiome Researchers at McMaster University’s Farncombe Family Digestive Health Research Institute are investigating how changes in the gut resident bacteria can lead to disease and developing strategies for diagnosis, treatment, and prevention.

R Abigail Cukier

esearchers are increasingly discovering the importance of our gut m ic robiome to ou r physical and mental health. Scientists and clinicians at McMaster University’s Farncombe Family Digestive Health Research Institute are making great strides in understanding how changes in the gut microbiome can lead to disease and are developing new strategies for the diagnosis, treatment, and prevention of digestive diseases.

Following the discovery that a single resident bacterium, Helicobacter pylori, could cause peptic ulcers and gastric cancer, McMaster University’s Intestinal Disease Research Program turned its

attention toward the microbiome. In 2003, it opened Canada’s first germ-free facility, which enables researchers to study mice that either have no microbes or have a prescribed microbial community, thus allowing the study of how resident bacteria interact with the host. In 2008, the program became the Farncombe Family Digestive Health Research Institute, focusing on the role of the microbiome in health and disease.

Our small and large intestines house trillions of bacteria, fungi, and viruses, which together are referred to as the microbiome. The microbiome is an integral part of us and helps maintain health. It’s influenced by genetics, stress, diet, and antibiotic exposure, and under certain circumstances can

predispose us to disease.

A major strength of the Farncombe Family Digestive Health Research Institute is its multidisciplinary approach, which involves collaboration between clinicians, clinician-scientists, and basic scientists. “This is important because we can conduct pre-clinical studies in the laboratory, take the findings, and test them in our patients. We can also take observations from our patients and investigate these problems in the lab. This, bidirectional translational research capability is of great benefit in understanding disease,” says Dr. Stephen Collins, Director of the Farncombe Family Digestive Health Research Institute and Professor of Medicine at McMaster University.

This page was sponsored by McMaster University and the Farncombe Family Digestive Health Research Institute.

Fecal transplantation to treat ulcerative colitis One important study at the institute is led by Dr. Paul Moayyedi, Director of Clinical Research at the institute and Professor of Medicine at McMaster University. “It was believed that ulcerative colitis and Crohn’s disease were autoimmune diseases, caused by your own immune system attacking the gut. All therapies, like steroids and biologics, were aimed at suppressing the immune system,” he says.

But Dr. Moayyedi wanted to study what was causing this immune reaction,

investigating how microbes might be driving it. He looked to fecal transplantation, which is the transfer of stool from a healthy donor into the gastrointestinal tract, usually to treat C. difficile.

Dr. Moayyedi’s lab, in collaboration with microbiologist Dr. Michael Surette, ran a randomized trial replacing the bacteria in the colon of patients with ulcerative colitis with healthy bacteria.

The study found that with a weekly transplant for eight weeks, about 25 percent of people will go into remis-

sion. These results are comparable to the effects of biologic therapy.

“This proves that if you alter gut bacteria, in some people, this can alter the disease. This is very strong evidence that ulcerative colitis is driven by an infectious agent in your colon,” says Dr. Moayyedi. “We’re not perfect yet, but if we understand better what we’re trying to modulate, we can effect a cure for this disease. That will take time, but we already have a therapy that could be an alternative for some people.”

Dr. Paul Moayyedi Director of Clinical Research, Farncombe Family Digestive Health Research Institute & Professor of Medicine, McMaster University

Connection between gut microbiome and mental health Dr. Premysl Bercik, a researcher at the institute and Professor of Medicine at McMaster University, is studying gut bacteria’s impact on mood and mental health.

“Animal data demonstrates that the behaviour of germ-free mice differs from conventionally-raised mice, who are born and raised with bacteria, along with differences in brain chemistry and

structure,” he says, adding that there’s increasing evidence that microbial profiles differ between patients with anxiety and depression compared to people with no mood disorder. Fecal transplantation from patients into germfree mice has also been found to induce anxiety and depressive-like behaviour.

In Dr. Bercik’s pilot clinical study,

patients with irritable bowel syndrome (IBS) who also had depression and/ or anxiety were treated with probiotic bacterium B. longum NCC3001. This treatment improved IBS symptoms and also improved depression scores after six weeks, which was accompanied by changes in activity of several brain regions that control mood and anxiety.

Gut microbes’ interactions with the food we eat could determine disease Dr. Elena Verdu, Associate Director of the institute and Professor of Medicine at McMaster University, studies gut inflammation in inflammatory bowel disease (IBD) and celiac disease. She explains that in celiac disease, gluten damages the lining of the gut in people with certain genes. But these are common genes, so Dr. Verdu studied why celiac disease occurs in some people and not in others. Her lab looked at how gut

microbes could determine whether or not you’ll get the disease.

“We found that people with celiac disease have certain microbes that feed on the gluten they eat, breaking down the gluten proteins into smaller pieces called peptides and those peptides, are better absorbed through the gut lining and can activate immune cells in celiacs,” she says. “While in most people, without the genes, this doesn’t cause any problems, in a person with the risk genes

it can lead to a higher susceptibility to develop the disease.”

Dr. Verdu says that there’s a crosstalk between our gut microbes, the foods we eat, and the cells in our body.

“When those interactions are equilibrated, they contribute to a healthy state,” she says. “But when there’s an imbalance in this interaction, then gut microbes and their metabolites can cause inflammation and contribute to IBD and celiac disease.”

Integrating scientific fields to increase understanding “We share our diet with our microbial partners,” says Dr. Stephen Collins, Director of the institute and Professor of Medicine at McMaster University.

“That means microbes can alter what we eat, for better or worse. We also rec-

ognize that diet is the most important factor that shapes our gut microbial community. We believe we can modify this community to promote health or treat disease by changing certain components of our diet. The way forward

is to adopt an approach that integrates nutritional science with microbial and intestinal research to optimize health and manage chronic conditions within and beyond the gut.”

Dr. Elena Verdu Associate Director, Farncombe Family Digestive Health Research Institute & Professor of Medicine, McMaster University