Augustin Scalbert is head of the Biomarkers Group at the International Agency for Research on Cancer (IARC) in Lyons, France (www.iarc.fr). His current research focusses on the development and implementation of metabolomic approaches in cancer epidemiology. Main objectives of his group are to discover novel biomarkers of exposure for dietary, environmental, and other lifestyle factors, and to identify risk factors for cancer and intermediate end-points through biomarker approaches. Robust methodologies developed in his lab for both targeted and untargeted metabolomic analyses have been applied in large multicentric epidemiological studies such as the European Prospective Investigation on Cancer and nutrition (EPIC) study and other EU-funded projects (EXPOsOMICS, TRANSCAN MetaboCCC). He developed the Exposome-Explorer database on biomarkers of exposure to disease risk factors (http://exposome-explorer.iarc.fr/). Before arriving at IARC in 2010, he conducted research at the National Institute of Agriculture Research (INRA) on the structure of lignins and tannins in lignocellulosic materials (INRA Grignon) and on the bioavailability and functions of dietary polyphenols in human nutrition (INRA Clermont-Ferrand). He has been identified as a Highly Cited Researcher (Clarivate Analytics).
1. When and why did you start using metabolomics in your investigations? I started using metabolomics about 15 years ago, when working on the health effects of dietary polyphenols. There were so many hypotheses on their biological effects and effects on human health and this made me feel that hypothesis-driven approaches were reaching some limits. This was particularly true in the field of nutrition research, with growing interest for many food bioactives like polyphenols, carotenoids, glucosinolates, phytates, etc. Many mechanisms of action had been proposed, largely based on in vitro studies, but few had been demonstrated in humans. Metabolomics offered a way to look at metabolic effects in a more comprehensive way in preclinical and dietary intervention studies. It became possible to compare the effects of food bioactive compounds on a large diversity of metabolic pathways, according to their magnitude, frequency or early onset, and to raise novel hypotheses on mechanisms of action. A second reason for my interest was the complexity of exposures to a huge number of compounds known in various foods. Here again, metabolomics revealed itself as a powerful approach to describe exposures to these natural compounds and to discover biomarkers of exposure for a large diversity of foods.
2. What have you been working on recently?
We are active in several research areas using metabolomics: - The identification of metabolic profiles associated with cancer outcomes in prospective epidemiological studies. We apply targeted and untargeted metabolomics approaches in case-control studies nested in large cohorts to identify metabolic features characterizing individuals who will later develop cancer. We can thus learn about mechanisms contributing to the risk of developing various cancers. - The discovery of novel biomarkers of dietary exposures suspected to play a role in the etiology of cancer and not easily assessed with dietary questionnaires commonly used in epidemiological studies. Recent work was focused on different types of coffee brews or on various processed meat products, respectively decreasing or increasing risk of some cancers. - The measurement of the internal exposome (all chemicals/metabolites that can be used as indicators of exposures to disease risk factors). We are partners in EXPANSE, a large European project, aiming at characterizing the urban exposome. As part of this project, we will analyze 10,000 blood samples from 15 different cohorts in Europe.
3. Do you think the identification of dietary biomarkers can aid in the prevention of specific types of cancer?
Many dietary biomarkers are now known, and some have been used in cancer epidemiology (http://exposome-explorer.iarc.fr/). Recent development of metabolomics has speed up discovery of novel dietary biomarkers. These biomarkers can be used to improve measurement of dietary exposures in epidemiological studies and strengthen the evidence on the role of dietary factors (food, nutrient or food constituent) in the etiology of different types of cancer. This evidence is regularly reviewed and constitutes the basis for cancer prevention.
4. What are the current challenges for discovering dietary biomarkers for cancer risk in large epidemiological studies ?
Two of the main challenges are the limited sensitivity of current methods and instruments to measure hundreds to thousands food compounds/metabolites in human blood or urine and the need for biological samples with high-quality metadata on dietary exposures and potential confounders. To address the first limitation, more sensitive targeted assays will be needed to measure large panels of dietary biomarkers. Dietary intervention studies are the gold standard to address the second limitation, but only a limited number of foods can be tested. Cross-sectional studies with high quality and highly detailed dietary data (e.g. from 24-hr dietary recalls) can also be used to cover a large diversity of foods.
5. What would your advice be for people getting started in food metabolomics?
I would say to have a good knowledge of food chemistry and metabolism, and secondly to have access to human samples from either dietary intervention studies or epidemiological studies. It is always possible to run your own intervention studies or to establish your own cohort study. This requires time and money. You can also collaborate with clinicians and epidemiologists, and bring knowledge and resources to run metabolomics analyses on human biospecimens they collected. This is what I did when developing this research first at the French National Institute of Agricultural Research (INRAe) and for the last ten years at the International Agency for Research on Cancer.
6. You are the Biomarkers Group Leader at the International Agency for Research on Cancer. What do you think contributed significantly to your career path in becoming a group leader?
Firstly, a desire for change and the wish to explore a new field of research, working with new people, in a new environment (about every 10 years in my own career, from wood chemistry to cancer epidemiology). Each of these changes was very demanding but also very rewarding. Secondly, the will of the Director of IARC at the time to start this new group to introduce metabolomics at IARC and develop its applications to cancer epidemiology, and lastly some experience in metabolomics, at a time when it was not as common as today.