Spotlight on Vincenzo Di Marzo

New Canada Excellence Research Chair will change the way you think about intestinal flora

In the dark depths of your stomach, somewhere inside your intestine, lives a system of micro-organisms. It’s called the gut microbiome, known more widely as intestinal flora. It is a big system—the gut microbiome can weigh up to 3 per cent of a person’s body mass—and it has probably partly co-evolved with human beings over the millennia.

These micro-organisms—mostly bacteria, archaea and fungi—usually live in symbiosis with your body: they help you to metabolize food, extract essential nutrients and keep pathogens at bay. If disturbed, however, they can cause big health issues, including diabetes, obesity and subsequent cardiovascular problems. At least, we think they do. The truth is that nobody knows exactly how they work, or what their role is. That, however, could be about to change.

Di Marzo has set himself the “fascinating, challenging project” of understanding the effect environmental cues have on the gut microbiome—and, consequently health—at the cellular and molecular level

Arriving at Université Laval is renowned biomolecular chemist Vincenzo Di Marzo. Di Marzo has just been named Canada Excellence Research Chair (CERC) in the Microbiome-Endocannabinoidome Axis in Metabolic Health, and in the summer of 2017 will become the university’s fourth CERC.

For the seven years he will hold this chair, Di Marzo has set himself the “fascinating, challenging project” of understanding the effect environmental cues have on the gut microbiome—and, consequently health—at the cellular and molecular level.

Subsequently, he aims to develop new strategies to restore the microbiome to good health. One of the ways he will do this is by taking advantage of “food-derived components that can positively influence the beneficial actions exerted by gut microbes through their own chemicals.” It is a task, he says, that is achievable.

“We already know a lot about the gut microbiome,” says Di Marzo. “We know its composition—primarily bacteria, viruses and yeasts—and that some are beneficial to the human body, and some less so. We also know that if we alter the relative composition of a person’s gut microbiome, there will be consequences for their physiology (i.e., their organs or systems). Indeed, there are strong links between this and inflammatory bowel disease and other intestinal conditions, obesity, metabolic and cardiovascular disorders, and even cancer.”

But why is this?

“This is what I hope to find out,” he says. “I want to examine the microbiome at a molecular level. I want to see how it communicates with the human body. We know that the gut microbiome comprises “good” bacteria and “bad” bacteria—and that these are usually well balanced. The gut plays a key role in various bodily functions, including metabolism and the immune system. But if the equilibrium of the microbiome is disturbed, a phenomenon called “dysbiosis” occurs: that has consequences for the body.”

This disturbance can be caused by environmental stressors such as heat, cold, drugs, pollution, and, particularly, good and bad dietary habits. Antibiotics, of course, also affect the microbiome, and may reduce the levels of “good” bacteria in the gastrointestinal tract and allow “bad” bacteria to flourish—as is the case of C. difficile. Fortunately, it is also possible to affect the gut microbiome in a positive way: one successful line of treatment for C. difficile is a fecal transplant, which involves taking a stool from a healthy person and transferring it to a patient. This repopulates the recipient’s microbiome with diverse micro-organisms that competitively exclude C. difficile.

“I want to know why this happens, how this improves things,” says Di Marzo. “Is there something in the microbiome that makes us feel better, something that brings about these kinds of therapeutic effects? And if so, can we develop more pleasant ways than fecal transplant to take this further? Can we design proper therapeutic applications for this and other types of pathological conditions?”

“I believe there are so many possibilities. I don’t think we’ve even seen the tip of the iceberg yet,” he adds.

One of the main thrusts of his research at Université Laval will be the role of the microbiome in causing obesity and metabolism-related disorders. This is timely: the latest statistics from the World Health Organization show that more than 1.9 billion adults worldwide are overweight—and of these, 600 million are obese. And in May 2016, United European Gastroenterology published a report that showed one in three children in Europe between the ages of six and nine were either overweight or obese.

“The need for this research is pressing,” says Di Marzo. “One of the main things I am going to look at is the link between the gut microbiome and the endocannabinoid system. This is an ancient chemical signaling system that, when stimulated by food shortage, makes us eat more food and accumulate more fat. It is a key player in controlling and managing energy metabolism: it intervenes in all aspects of energy homeostasis and, like the microbiome, its activity is modulated by stress factors and dietary habits.”

The first important links between endocannabinoids—and even some members of the wide family of related chemical signals that comprise the “endocannabinoidome”—have already been established.

“I believe that the same environmental stressors affect both the microbiome and the endocannabinoidome and that perturbations of either system ricochet on each other, with impact on metabolic and related disorders. If we understand this crosstalk from the molecular point of view, we shall have the basis to develop new weapons to combat dysbiosis and hence its cardiometabolic consequences,” says Di Marzo.

The social and economic benefits of this research are clear. Obesity contributes to the increased prevalence of cardiovascular disease, diabetes, high blood pressure, stroke, pulmonary embolism, osteoarthritis and some cancers. In 2015, Statistics Canada estimated that 3.5 million Canadians were living with type 2 diabetes—an obesity-linked metabolic disease that costs the country more than $14 billion.

 I believe there are so many possibilities. I don’t think we’ve even seen the tip of the iceberg yet 

“Coming to Laval is an unmissable opportunity,” says Di Marzo. “I will be working with two faculties [Medicine, and Agriculture and Food Science] and two of their best known research centres [respectively the Institut universitaire de cardiologie et de pneumologie de Québec and the Institut sur la nutrition et les aliments fonctionnels] to develop nutritional and medical strategies to fight obesity. And this is in a context where the presence of three other CERCs provides an opportunity for multidisciplinary collaboration.”

Furthermore, the creation of a Joint International Research Unit between Université Laval and the Italian National Research Council will provide the necessary facilities and expertise in structural chemistry and innovative drug delivery technologies.

“First, however, we have to really understand what the microbiome does, what its role is,” says Di Marzo. “In the past, my research has helped develop new therapies from a controversial natural source (cannabis), which led to the development of terms such as endocannabinoid and endocannabinoidome. I hope I will be able to use this experience to derive other therapies from a difficult-to-handle, and completely different, source: the gut microbiome. Who knows where that might lead us.”