Discoveries and Innovations
Caroline Duchaine and research on bioaerosols at CRIUCPQ
Bioaerosols are everywhere. These particles of biological origin include bacteria, viruses, moulds and pollens. These airborne microorganisms are so ubiquitous that is almost impossible to describe a context where they are not present. They are involved in several infectious diseases in humans, animals, plants or other types of health conditions such as asthma or hypersensitivity pneumonitises. The study of bioaerosols is a complex science, multidisciplinary, that was developed in the 1950s in order to prevent laboratory infections. We subsequently focused on understanding work-related diseases such as professional asthma, farmer’s lung and organic dust toxic syndrome. Molecular analytical methods in microbiology appearing in the early 2000s have helped considerably enriching the knowledge in the field and allowed researchers to respond to questions that remained unanswered. Our laboratory is pioneering in the use of molecular methods for characterizing and studying bioaerosols.
Our research program developed around the issue of occupational respiratory health: farmer’s lung disease, exposure in dental office or alveolitis among peat moss workers. But we did manage to consolidate our program and having it evolve to demonstrate that bioaerosols may be a problematic factor for respiratory health in an industrial setting as much as it can be for animal or human health. The emergence of the Porcine Epidemic Diarrhea virus or the crisis for Legionnaires’ disease is an example of events studied by my team to leverage its research and help resolve serious societal issues.
The expertise of the team is leveraged to face major environmental issues associated with climate change such as exposure to new infectious agents, the long-range transport of bioaerosols and the protection of populations against emerging pathogens and multidrug-resistant bacteria. The COVID-19 pandemic is a new opportunity for my team and me to deepen our knowledge of this disease regarding our studies on bioaerosols. We are involved in, among others, several research projects to study the role of air in the spread of the virus responsible.
My lab houses a vast fleet of equipment that will enable us to cover most aspects of research on bioaerosols: microbiology, industrial hygiene, medicine for humans (respirology and infectious diseases) and animals (livestock), microbial ecology, public health and industrial processes.
My team designed and built several chambers and tunnels dedicated to the behaviour of bioaerosols and to the development of control strategies. We can indeed study the infectious disease transmission with animal models, the effect of various chemical or physical agents to destroy viruses in the air, the efficiency of devices for capturing bioaerosols or the situations fostering their aerosolization and consequently, the human exposure.
Several of our projects include components to document workers’ respiratory health in different contexts as in industrial and agricultural sectors. In collaboration with respirologists and infectiologists, so we can correlate the exposure to bacterial, fungal, viral or archaeal bioaerosols with various symptoms. Our team thereby described many occupational situations where exposure to bioaerosols is of concern: dairy farms, egg production, hog barns, sewage system plants, dentists, health workers or sawmills and peatlands.
We developed, over the last few years, a keen interest in bioaerosol control and engineering approaches. So we contributed to several projects targeting technology development, such as percolating filters, ozone, spraying with oil or antimicrobial filtration. Application and development of molecular methods in addition positioned us as a leader in studying air microbiota and developing tools in bioinformatics to interpret DNA sequencing data, especially for the fungal microbiota.
The research on bioaerosols is one that is integrative, cross-sectoral and multidisciplinary to countless benefits. Our team enjoys a fruitful collaboration with several researchers and clinicians from the Research Centre of the Institut universitaire de cardiologie et de pneumologie de Québec (CRIUCPQ) and we are proud to contribute to advancing knowledge on the impacts of microorganisms in the air on human health.
Mathieu Laplante – Limited Non-Surgical Means to Combat Obesity in Humans
Individuals are increasingly affected by obesity and this condition is linked to many illnesses such as type 2 diabetes, insulin resistance, dyslipidemias and cardiovascular diseases. This situation is particularly alarming because the effective means (non-surgical) that help reduce obesity and maintain body weight in humans are still limited. Accumulation of adipose tissue, mainly in the abdominal cavity, is recognized as contributing to deteriorating the metabolic profile and to increase the risk of cardiovascular diseases. This adipose tissue, which is drained by the portal vein, releases toward the liver high amounts of lipids and pro-inflammatory factors. Liver overexposure to these factors induces the accumulation of lipids in it, a condition known as the non-alcoholic steatohepatitis.
The fat deposition in liver contributes to insulin resistance and atherogenic dyslipidemias, and increase susceptibility to cardiovascular diseases. The precise molecular mechanisms by which the non-alcoholic steatohepatitis is contributing to alter the function of peripheral tissues are still not fully understood. Researchers demonstrated that, over the last few years, liver secretes numerous proteins affecting other tissue functions and contributing to exacerbating metabolic disorders in people suffering from hepatic steatosis. These proteins, named hepatokines, are seen today as potential therapeutic targets for improving metabolism in obese.
We initiated in 2013 a research project aimed at identifying and characterizing new hepatokines secreted in response to hepatic steatosis. We put in place a simple analysis platform that exploits gene expression data publicly available in order to identify new hepatokines. Several new proteins mainly expressed in the liver and capable of being secreted in the blood circulation can be identified based on this analysis. We then verified to what extent the production of these hepatokines is affected in the liver of a lot of obese mouse models. These experiments allowed us to identify the protein named Tsukushi (TSK), as a new hepatokine overproduced in the context of obesity. Our studies determined that lipid accumulation and liver inflammation contribute to increasing the production and secretion of TSK. These observations were made in mice and later confirmed in cohorts of human patients. In order to define the functions of TSK and its impact on metabolism, we generated transgenic mouse models allowing us to overproduce or repress its expression. These animal studies indicated that TSK does not affect the development of hepatic steatosis, but plays a key role in regulating cholesterol metabolism. We discovered that TSK reduces specifically the HDL cholesterol levels, also known as “good” cholesterol. HDL plays key roles in preventing cardiovascular diseases by fostering the removal of cholesterol from arteries and peripheral tissues. We observed that the presence of TSK into the circulation is reducing the cholesterol returning to the liver and its excretion in the bile. Our results support a model in which the liver congested of lipids overproduces TSK to limit the cholesterol that returns and protects itself against the excess of them. These results suggest that TSK could help the development of cardiovascular diseases by promoting the accumulation of cholesterol in peripheral tissues. We thereby propose that hepatokine TSK might be a new link between hepatic steatosis, atherogenic dyslipidemias and developing cardiovascular diseases.
Our work on TSK was published in 2019 in the journals JCI Insight and Molecular Metabolism. These studies were made possible through sustained collaboration of several researchers from the IUCPQ, in particular Dr. André Marette, Dr. Mathieu Morissette and Dr. Philippe Joubert. Other teams from Université Laval, Université de Montréal and University of Alberta also played an important role in our work. It is of importance to finally highlight the funding contribution of various organizations to achieving our work. These include the Foundation of the Institut universitaire de cardiologie et de pneumologie de Québec – Université Laval (IUCPQ-UL), the Canadian Institutes of Health Research (CIHR), the Fonds de recherche du Québec – Santé (FRQS), the Cardiometabolic Health, Diabetes and Obesity Research Network (CMDO), the Quebec Bio-Imaging Network (QBIN), Diabètes Québec and Merck Sharpe & Dohme Corp./Faculty of Medicine at the Université Laval.
André Marette – Are Bacteria Involved in the Development of Type 2 Diabetes?
Bacteria might be involved in the development of type 2 diabetes, according to the study of Dr. Marette’s team, bringing together researchers from Université Laval, Institut universitaire de cardiologie et de pneumologie de Québec – Université Laval (Institute) and McMaster University published in the journal Nature Metabolism. Researchers report that blood, liver and certain abdominal fat deposits from people with diabetes present a different bacterial signature from that observed in non-diabetics.
Researchers proved this point with blood samples and tissues collected from 40 people with severe obesity when they underwent a bariatric surgery. Half of participants were suffering from type 2 diabetes while other subjects were insulin-resistant without being diabetic.
The team did the detection of bacterial genetic material on each tissue collected, coming from the liver and three fatty deposits from the abdomen. The type of bacteria present and their relative abundance allowed researchers to establish the bacterial signature of each tissue. Analyses revealed this microbial signature of people with diabetes was different from that of non-diabetics. They also showed that the bacterial relative abundance was varying among tissues and it was reaching a maximum in the liver as well as the great omentum (a fatty tissue interconnecting the stomach and the transverse colon), two sites heavily involved in metabolic regulation.
“Our results suggest that, in people suffering from severe obesity, bacteria or bacterial fragments are associated with the development of type 2 diabetes,” summarizes the responsible for the study, Dr. André Marette, researcher at the Institute’s Research Centre and professor at the Université Laval’s Faculty of Medicine.
The bacterial genetic material that has been detected in these tissues most likely comes from the intestine, according to researchers. “We know that the tightness of the intestinal barrier is reduced in obese,” reminds Dr. André Marette. “Our hypothesis is that live bacteria or bacterial fragments cross this barrier and trigger an inflammatory process, which ultimately prevent insulin from fulfilling its role of regulating blood glucose levels, via its action on metabolic tissues.”
Dr. Marette and his collaborators will be able to further their research through a grant of $2 M just given recently by the Canadian Institutes of Health Research (CIHR).
“Our next objective is to determine if bacteria found in the liver and fatty deposits of people with severe obesity are also present in obese or in those who are overweight,” explains Dr. André Marette. We also want to verify if some of the pathogenic bacteria found in tissues can trigger type 2 diabetes in an animal model. We finally want to know if certain beneficial bacteria in these tissues can be used to prevent the development of this disease. They might represent, if that was the case, a new family of probiotic bacteria or a source of bacterial molecules to help combat diabetes,” concludes the doctor who is also a member of the Institute of Nutrition and Functional Foods (INAF) at Université Laval.