Feb. 18, 2017

Microbiome: The ‘forgotten organ’

Each of us lives with trillions of bacteria, viruses, parasites and fungi in and around our bodies. UCalgary researchers study the impact this "microbiome" has on our health, and how our sanitary practices could be harming us.

When Anastasia Chin-King was born, she was one of millions of babies born every year who need an aggressive course of antibiotics to treat a urinary tract infection. Those antibiotics may have saved her life, but they also wiped out her developing microbiome — the trillions of bacteria, viruses, parasites and fungi that live in and around every one of us.

We all have a unique set of cells in and around our skin, our mouths, our gut, etc. In each area, these cells are known as microbiota — for example, the “oral microbiota.” Together, they make up the microbiome, the largest organ in the body. It's “the forgotten organ,” says Dr. Paul Kubes, PhD, a professor in the University of Calgary's Cumming School of Medicine, and director of the Snyder Institute for Chronic Diseases.

“It makes up more cells than all the rest of your body put together and we’ve completely ignored it,” says Kubes. “It’s only now that we’ve realized we’ve got an organ that nobody has ever studied and we’re realizing how important it is to our daily lives. It's absolutely critical.”

“It makes up more cells than all the rest of your body put together and we’ve completely ignored it."

Anastasia’s mother, Dr. Ajitha Thanabalasuriar, PhD, is a postdoctoral fellow in vascular immunology and one of dozens of UCalgary researchers trying to understand the microbiome and how it affects our health and wellness. Through the new Western Canadian Microbiome Centre (WCMC), scholars are discovering how we can use the microbiome to prevent and treat a number of diseases, from autism and asthma to obesity and irritable bowel syndrome.



A billion bacteria at birth

The microbiome starts developing at birth and continues to change until about age three. During birth, a baby moves from a sterile environment in utero, down the birth canal where he or she is exposed to and colonized with their mother’s microbiota. Within the first hour of its life, a baby can be exposed to a billion bacteria.

“Babies born through a vaginal birth have microbiota that resembles their mother’s vaginal microbiota, whereas babies born by caesarean section have microbiota that often looks more like a skin microbiota,” says Dr. Kathy McCoy, PhD, professor in the Cumming School of Medicine and director of the WCMC.

“Diet, exposure to the mother, early life antibiotics — all of these put a lot of pressure or changes on the microbiota,” explains McCoy. “As it’s developing, it’s quite heavily influenced by the environment.”

Things to remember:

  • A baby starts developing a microbiome at birth.
  • Antibiotics can drastically reduce and alter an infant’s microbiome, setting them up for disease later in life.

Microbiome and the immune system

An infant’s microbiome communicates with their immune system, sending molecular signals to help set up or "program" the immune system to protect them and keep them healthy for the rest of their life.

The immune system needs signals from a wide variety of microbiota. If, for some reason, an infant’s microbiome doesn’t develop with the right mix and amount of bacteria (because, for example, antibiotics for an infection wiped it out), it can’t provide the immune system with all the information it needs. 

"There is a critical window of development."

“It seems like there is a critical window of development where if you miss some sort of education from microbiota at this time, it’s too late. You can’t get it back later,” says McCoy. “The immune system is no longer receptive. That development window has passed.”

Researchers think this missed opportunity to set up the immune system may increase the child’s susceptibility to a wide range of allergies, autoimmune disorders and other diseases later in life.

“Microbiome tells you what kind of immune system you should have," says Kubes, a world leader in studying chronic disease and Canada Research Chair in Leukocyte Recruitment in Inflammatory Disease. "If you don’t have the right immune system, then you’re going to develop chronic disease.”

We know the microbiome plays a role in every system of our body and is important in maintaining good health. It may also influence a staggeringly long list of illnesses and disorders that affect billions of people around the world.

“Heart disease, diabetes, metabolic disorders, obesity, arthritis, autism, Alzheimer’s, Parkinson’s — there is a huge range of studies going on,” says McCoy. “It’s time to tease out on a basic level what are these interactions and how the microbiome impacts these different things.”

Does the microbiome cause disease? If we change the bacteria in your body, can we prevent disease? It’s an emerging area of research that is illuminating the incredibly complex relationship between our microbiome and our health.

“You have 300 trillion bacteria in your colon and they’re all producing molecules,” says Kubes. “If they’re producing the wrong molecules that get into the blood stream they could make your neurons fire the wrong way and now you get a disorder like autism. That’s the thinking.”

Things to remember:

  • The microbiome sends molecular signals to help set up the immune system to keep a baby healthy for life.
  • The microbiome plays a role in every system of the body and is important in maintaining good health.


Finding more answers

The new Western Canadian Microbiome Centre will include state of the art equipment, techniques and technologies to help researchers find answers about the microbiome’s influence on our health and wellness. When the facility is completed in May 2017, it will be the largest academic germ-free facility in Canada and perhaps the world.

“We will take away all the microbes in animal models so they’re basically like an empty vessel," says McCoy. "We’ll study what the immune system looks like when we have no interaction at all. Even more powerful is now we can add back specific bacteria to the germ-free host and then monitor the impact on the immune system or any other body system we wish to study. We will image what’s happening to the bugs as well as to the immune system at multiple different levels.”

The WCMC supports scholars with expertise from a number of different fields, from engineering to veterinary medicine, who are studying the microbiome of humans, animals, plants and the environment.

"There is a staggering scale of complexity there."

Biochemist Dr. Ian Lewis, PhD, studies bacterial metabolic pathways to understand dangerous infections such as antibiotic-resistant superbugs and other hospital-acquired infections. “There is a staggering scale of complexity there that has to be decoded,” says Lewis, an assistant professor and AIHS Translational Health Chair-Metabolomics in UCalgary’s Faculty of Science.

Lewis likens bacterial metabolism — the complex process bacteria use to digest their food — with how you drive different highways across the country: “The route that you take has a big impact on how much energy is involved in getting there," he says. "How many miles do you have to drive, how much gas you have to burn. It also has a big impact on where you end up and what you can do when you get there. We study how much traffic goes down each of these metabolic routes.”

By understanding how bacteria acquire and digest their food at the molecular level, researchers can identify the most dangerous bacteria — pathogens — and develop ways to stop them. “We believe the most dangerous pathogens select for certain kinds of pathways,” says Lewis. “And we’re developing new technology that allows us to identify those pathogens and, we hope, give us leverage to control them.”

That’s crucial in light of the looming crisis of antibiotic-resistant bacteria. “Knowing how bacteria, cells, and other organisms are able to function, how much energy they have to do things, will really enable industrialists and clinicians to develop products and methods that will save lives,” says Austin Nguyen, a fifth year biological science student who works in Lewis’ lab.

Things to remember:

  • Antibiotic resistant bacteria are a growing threat to world health.
  • The way bacteria digest their food affects how quickly they grow and how dangerous they can be as pathogens. Studying bacterial metabolism may lead to new diagnostic tools and treatments.


Microbiome's staggering scope

Research into the microbiome holds tremendous potential for personalized medicine, an emerging field in which specific treatments are developed using your own individual cells. And it may yield a number of solutions to social problems beyond human health, including reducing food waste by understanding bacterial spoilage, increasing food production in agriculture and livestock, and even reducing carbon emissions by exploring how microbiomes can convert biomass into alternative energy and change the composition of CO2 emissions.

“The emerging discoveries in this area have very broad applications across society,” says Kubes. “Microbiome research is new and very exciting and has potential to improve therapeutic and diagnostic technologies for our health and the environment around us.” 

This enormous potential to improve society is dependent on an army of researchers working on impossibly tiny pieces of a giant puzzle. From Ian Lewis looking at metabolic pathways to Ajitha Thanabalasuriar studying how cells in the lungs patrol for and kill foreign particles, researchers at the University of Calgary are adding to the growing understanding of the microbiome. 

“The more we understand about the microbiome," says Thanabalasuriar, “The more chance we have to stop the development of diseases.”

Things to remember:

  • Microbiome research has the potential to improve therapeutic and diagnostic technologies for our health.
  • Research into the microbiome may yield solutions to a wide variety of other problems in society from food waste to reducing carbon emissions.

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Dr. Paul Kubes, PhD, is a professor in the University of Calgary's Cumming School of Medicine, and director of the Snyder Institute for Chronic Diseases. His research interests are in models of acute and chronic inflammation, studying how different leukocytes (neutrophils, monocytes and lymphocytes, etc.) traffic to sites of inflammation, and the role of different immune receptors in the initiation of inflammation. Read more about Paul

Dr. Kathy McCoy, PhD, is a professor in the Cumming School of Medicine and director of the Western Canadian Microbiome Centre. View Kathy's publications

Dr. Ian Lewis, PhD, is an assistant professor and AIHS Translational Health Chair-Metabolomics in UCalgary’s Faculty of Science. His research focus is on investigating the connection between metabolic adaptation and virulence of human pathogens, with the ultimate goal of developing new diagnostic methods to identify high-risk patients and novel antimicrobial therapies to control infections. Read more about Ian

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