Dec. 17, 2019

Do our brains and guts talk to each other? Exploring the signals between the major control centres of our bodies

We think most of our bodies' directives come from our brains, but research shows more and more that much of what happens in the body is driven by what's going on in the gut

Got a gut feeling about something that might happen in your life today? You’re not alone.

“Whether we know it or not, we’ve all experienced the sensation of the connection between our gut and our brain,” says Dr. Braedon McDonald, MD, PhD, an assistant professor in the departments of Critical Care Medicine and Medicine and a member of the Snyder Institute for Chronic Diseases in  UCalgary's Cumming School of Medicine. “People with an upset stomach or the feeling of butterflies when nervous or anticipating — they're demonstrating that our gut and brain are connected.”

As you read this, the trillions of cells in and on your body that include fungi, viruses and bacteria are active, comprising what’s known as the human microbiota. The microbiome is the genetic material of these cells, and your gut is home to the majority of these microbiota.

The gut microbiome can play a role in brain function, as well as immune response, nutrition and metabolism, says McDonald.

We’re only beginning to understand how this ecological community of microorganisms in our gut can impact our well-being, physiology and even psychology. For example, most of the body’s supply of serotonin, which can affect gastrointestinal activity and mood, is manufactured by gut bacteria.

The enteric nervous system in the gut can operate independently of the brain and spinal cord, so the gut is considered by many researchers to be a second brain. That doesn’t mean it’s capable of thought, but scientists are recognizing that the gut and brain are constantly in communication in a system known as the gut-brain axis.

We know that as biochemical signals travel along a two-way communications pathway, this intricate chatter between the gastrointestinal tract and the central nervous system may hold the key to better health.

Many conditions have been linked to the microbiome, including inflammatory bowel disease, multiple sclerosis (MS), cancer and autism. So, consideration of the microbiome’s potential influence on health has fueled a surge of microbiome research.

Microbiome Centre spearheads research

UCalgary's International Microbiome Centre is at the forefront of exploring this relatively new frontier.

Dr. Kathy McCoy, PhD, the centre’s scientific director, spearheads and coordinates efforts in Canada to understand how the microbiome works and if it can be harnessed to improve human health.

She's brought together  top microbiome experts from across Canada in the Integrated Microbiome Platforms for Advancing Causation Testing and Translation (IMPACTT). This cross-disciplinary collection of scientists will provide advice and help to develop protocols for microbiome research.

We have the largest academic germ-free facility in the world, ​and are working towards a $50-million research program that has people and institutions working together on the world stage,” says McCoy, a professor in the Department of Physiology & Pharmacology and a member of the Snyder Institute for Chronic Diseases. “We’re studying the microbiome in ways that are innovative, interdisciplinary and impactful.”

Scientists uniformly understand the microbiome is complex and presents many challenges, given that each individual has a unique microbiome composition. It may change through life and be affected by the environment.

If the gut-brain axis relies to a degree on the interaction of microbes, are there good and bad gut bacteria? And, if so, how can we ensure we’ve got the right balance?

The idea of good and bad gut bacteria is all about balance and context.

“The idea of good and bad gut bacteria is all about balance and context,” says McCoy, whose own research focuses on immunity and exposure to microbes at birth. “What we want is the right bacteria in the right place in our guts in the right balance at the right time.”

Beneficial microbiota is called “commensal,” helping to bolster immunity by fighting invading microbes. Generally, disease is considered to be a sign of imbalance, which can often be caused by an overactive immune response, says McCoy. This imbalance can contribute to an increase of inflammatory or autoimmune disorders and allergies.

Much of the bacteria we have are considered commensal, so we live in harmony with them, says McCoy. When there is an imbalance, they can become harmful and grow to larger quantities than they normally should.

This changes the niche inside the gut where they live and they can become more opportunistic pathogens, she says. “Normally they would be considered a good bug, but when the balance is gone, some of the good bugs can turn bad.”                                                                                                               

When you have a disease, there's an alteration in the composition of the microbiota, called dysbiosis. A decrease in the level of microbial diversity has been be associated with a range of disorders including autism. Gut microbiota dysbiosis is also known as intestinal or gastrointestinal dysbiosis, a condition in which there is an imbalance of the microorganisms within our intestines.

Evidence suggests bacteria are involved when things go wrong in autoimmune diseases such as MS. Some research has shown MS patients have less than normal lactobacillus bacteria but more than normal ruminococcus bacteria.

McCoy and Dr. Pere Santamaria, MD, PhD, revealed a connection between the microbiome and autoimmune disorders in their research published in the journal Cell. They showed a link between the gut microbiome and inflammatory bowel disease. (Santamaria is a professor in the Department of Microbiology, Immunology & Infectious Diseases, a member of the Snyder Institute for Chronic Diseases and the Hotchkiss Brain Institute.)

Best conditions for healthy newborn microbiota

The microbiome of newborns changes and adapts through stages, research has shown, though much less is known about whether the microbiome progresses or regresses in normal human adults. The science so far is inconclusive on whether the process of aging results in changes in the gut that negatively affect health.

In the aging process, timing is everything. Birth is a good example of needing the right bacteria at the right time, says McCoy, who advises on ways to ensure babies get proper exposure to microbes that will contribute to their health over their lifetimes.

The first microbiota that a newborn baby should be exposed to, and colonize with, normally comes from the mom through vertical transmission (the passage of a pathogen to the baby by the mother during the period immediately before and after birth), says McCoy.

“Beginning with when a baby starts to get colonized with this microbiota, there appears to be solid evidence that the first 1,000 days are critical to the baby’s immune and brain development,” she says.

The microbiome in adults is believed to be relatively stable from the age of three or four and onward, if you are a healthy person eating a healthy and normal diet.

We believe strongly that in utero, the developing fetus is in a sterile environment, so it's not colonized with its own bonafide microbiota,” says McCoy. “We think the colonization with live bugs actually starts during the birthing process.”

This process starts when the membrane breaks and the baby is exposed. In natural vaginal birth, the baby is exposed to fecal and vaginal microbes that can be beneficial to its health, particularly contributing to its immune development, says McCoy, who has published her study findings in the journal Science.

This microbial transfer process is disrupted with Caesarean section births.

“When a baby is born with a C-section, they don’t get the same microbes,” says McCoy. “We know that people born via C-section  have an increased risk for developing allergies and disease.”

McCoy cautions against saying that across the board, all babies born in a C-section are more vulnerable to disease.

“It is multifactorial, so we can’t say every baby in a C-section birth will develop, say, an allergy. My advice is that if you have choice, I would not recommend an elective C-section. You should try and have a vaginal birth, but if it risks harming the baby, then clearly not. “

C-sections are a major surgery and I'm concerned about the rising rates.

Dr. Jaelene Mannerfeldt, MD, a Calgary obstetrician, gynecologist and clinical assistant professor in the departments of Obstetrics & Gynaecology and Family Medicine, delivers more than 250 babies annually. She believes that education for mothers, particularly when they're deciding whether to have a C-section or natural childbirth, can be improved, as the procedure can pose varied health risks such as blood loss and infection.

“C-sections are a major surgery and I'm concerned about the rising rates in Canada,” says Mannerfeldt, who is director of quality enhancement and safety in the Department of Obstetrics and Gynecology for Alberta Health Services.

“The procedure is often a first choice, but not always medically necessary. Women have a lot of choices in North America, which is good, but the main concern should be how can you bring this baby into the world so it can be safe and healthy.”

There were 104,349 C-sections performed in Canada during 2017-18, compared to more than 103,000 the previous year, even as birth rates decline — and C-sections topped the list of inpatient surgeries, according to the Canadian Institute for Health Information (CIHI).

McCoy also recommends that, if and when possible, breast feeding feeds the microbiome better, rather than baby formula, ensuring that the baby is getting the right microbes at the right time.

Finding the right balance

Just as we are all born, we will all very likely spend time in a hospital during our lifetime, where we can be vulnerable to infections.

The body’s good bacteria that are so helpful during health can occasionally turn bad when our defences are weakened, says McDonald, a specialist in intensive care. He’s doing research at Foothills Medical Centre  in Calgary, directly related to the question of microbial balance and disease.

“These intensive care unit (ICU) patients are often very prone to getting infections,” says McDonald, a clinician-scientist with the International Microbiome Centre. “Many of these infections are caused by bacteria living in our body that are normally so helpful. So, how can we build up immunity and restore the microbiome?”

ICU patients are often very prone to getting infections.

The ICU is where we look after patients who are critically ill and who require life support therapy, he says. When people undergo this degree of stress, their defences are weakened, affecting their immune systems.

The Micro ICU study, launched this past summer and running for two years, aims to define the balance between microorganisms and the immune system. Next steps will include using the study’s information to design therapies, says McDonald.

“We’ll look at providing beneficial microbes to restore that balance and repopulate the gut in a way that repairs the microbiome and the immune system so that we can prevent, not just treat, people from developing problems.”

Now, researchers are zeroing in on how these microbes function and interact at different times in the aging process, including the times when we’re healthy and the times when we’re fighting disease. The next step will be developing therapeutic approaches that can target diseases to remedy them and, at times, work as a preventative.

U.S.-based InSilico Medicine, an artificial intelligence start-up, has used machine learning to analyze gut bacteria data collected from 1,165 healthy people from across the planet. Using an algorithm, they developed a program that accurately predicted someone’s age within four years.

Next steps for researchers and clinicians include narrowing down which bacteria can be accurately associated with life stages such as youth and old age, as well as determining how particular bacteria can influence health during a lifespan and how they may be manipulated to do so.

How to eat healthy

Given the potential for modulating communications between the gut and the brain to achieve better health, researchers are considering the impact of food and nutrition on the human microbiome.

You can never go wrong with fibre, which is like fertilizer for the microbiome, says McDonald. Try and stay away from processed foods if you want to eat healthy. Foods that help to ferment fibre and make short-chain fatty acids are beneficial to your health and contribute to sustaining your microbiome. Bacteria in the gut produces short-chain fatty acids, which are a major source of nutrition for cells.

What we eat and how it impacts us loops back to McDonald’s observation that our gut and brain are connected. Eating the right stuff is just one way to bolster this vital, two-way communications pathway along the gut-brain axis. Exploring it with new research may ultimately lead us toward better health.


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Dr. Braedon McDonald, MD, PhD, is an assistant professor in the departments of Critical Care Medicine and Medicine and a member of the Snyder Institute for Chronic Diseases at UCalgary's Cumming School of Medicine. Read more about Braedon

Dr. Kathy McCoy, PhD, is a professor in the Department of Physiology & Pharmacology, scientific director of the International Microbiome Centre, and a member of the Snyder Institute for Chronic Diseases at the Cumming School of Medicine. Read more about Kathy

Dr. Jaelene Mannerfeldt, MD, is a Calgary obstetrician, gynecologist and clinical assistant professor in the departments of Obstetrics & Gynaecology and Family Medicine.

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