Heterogeneity in Nutrition and Metabolic Health
Virtual Workshop Report Summary

Event description

On October 13-14, 2022, the CIHR-Institute of Nutrition, Metabolism and Diabetes (INMD) hosted the Heterogeneity in Nutrition and Metabolic Health virtual workshop. The workshop was attended by researchers from across Canada and internationally. The aim of the workshop was to facilitate engagement and stimulate a robust discussion highlighting critical knowledge gaps and scientific opportunities related to heterogeneity in nutrition and metabolic health.

Workshop objectives

The primary objectives of the Heterogeneity in Nutrition and Metabolic Health virtual workshop were to bring together researchers and other stakeholders to:

• define the scientific opportunities, research gaps and priorities that could be addressed through a strategic research initiative on heterogeneity in nutrition and metabolic health;
• identify the Canadian strengths that could be leveraged to support a strategic research initiative on heterogeneity in nutrition and metabolic health;
• identify the potential structures needed to enhance collaboration and advance research in this field; and
• identify a list of potential partners, including international collaborators, who could work with CIHR to support a potential research initiative focusing on this topic.

Background

In 2021, INMD released a new strategic plan for 2021-26 with a vision of catalyzing world-leading research that promotes optimal and equitable nutrition and metabolic health outcomes for all Canadians. In the past few decades, the understanding of metabolism has evolved and shifted from a lens of pathways and mutations to encompass a wide range of dynamic physiological processes linked to health and disease across the lifespan.

It is increasingly clear that one-size-fits-all approaches to disease diagnosis, care, treatment, and prevention have limited effectiveness. Differences at the individual and population level with regard to genetic, molecular, structural, systemic, and environmental factors contribute to heterogeneity that significantly impacts the maintenance of health and prevention of disease, the effectiveness of diagnostic tools, treatment approaches (including precision medicine), and the aim to achieve health equity.

Historically, the term “heterogenous” was reserved to describe aspects of a disease or condition that we do not quite understand. In an era filled with unprecedented advances in tools, platforms, technologies, and therapies that can help elucidate and address heterogeneity, there is an urgent need to transform traditional approaches to disease prevention and management from a one-size-fits-all to precision medicine.

Workshop presentations

This workshop brought together Canadian and international researchers and stakeholders from a wide variety of fields to address the following topics:

Session 1: Interactions between structural, environmental, and biological factors in Indigenous communities that underlie heterogeneity in nutrition and metabolic health

Co-chairs: Tracey Prentice and Julie Ho

• Indigenous food sovereignty: Promoting nutrition and well-being
  Treena Wasonti:io Delormier ­– Associate Professor, Canada Research Chair (Tier II) in Indigenous Peoples’ Nutrition and Food Sovereignty, Associate Director, Centre for Indigenous Peoples’ Nutrition & Environment (CINE), McGill University
• Food security and food sovereignty as a determinant of health and chronic disease
  Lynden (Lindsay) Crowshoe – Associate Professor of Medicine at the University of Calgary and the Assistant Dean at the Indigenous, Local and Global Health Office
• Knowledge exchange between Indigenous communities and researchers studying gene-environment interactions informs nutritional interventions for type 2 diabetes in Indigenous youth
  Vern Dolinsky ­– Associate Department Head and Associate Professor, University of Manitoba
• Building community from Indigenous food security
  Raven Swamp­ – Greenhouse Facilitator, Karonhianónhnha Tsi Ionterihwaienstáhkhwa

Session 2: Precision nutrition approaches to understand heterogeneity and intervene effectively

Co-chairs: André Tchernof and Sharon Kirkpatrick

• Precision nutrition, precision health, and precision public health: Conceptual and methodological consideration for shifting the paradigm
  Lise Gauvin­ – Professor, Department of Social and Preventive Medicine, Université de Montréal
• The importance of considering the social and structural determinants of health in precision nutrition: Implications for promoting nutrition equity
  Angela Odoms-Young – Associate Professor and Director of the Food and Nutrition Education in Communities Program (FNEC) and New York State Expanded Food and Nutrition Education Program (EFNEP)
• Using multiomics approaches to decipher the heterogeneity of metabolic response to nutritional or weight loss interventions
  Marie Claude Vohl – Canada Research Chair in Genomics Applied to Nutrition and Metabolic Health, Professor, School of Nutrition, Laval University
• Deconstructing the complexity of eating behaviour: Contributions of gene-environment interactions
  Daiva Nielsen – Assistant Professor, School of Human Nutrition, McGill University
• The need to identify functional genetic variants that change metabolism
  Steven Zeisel – Professor, Gillings School of Global Public Health, University of North Carolina at Chapel Hill

Session 3: Understanding heterogeneity using multiple forms of data and tools

Co-chairs: Marc Prentki and Christopher Rose

• Precision nutrition for population health
  Saurabh Mehta ­– Director, Center for Precision Nutrition and Health, The Janet and Gordon Lankton Professor Division of Nutritional Sciences, Cornell University
• Host microbiome interaction in health and disease
  Eran Elinav ­– Head, Systems Immunology Department, Weizmann Institute of Science
• Diet and health: What’s good for you
  Jacques Corbeil – Canada Research Chair in Medical Genomics, Professor, Department of Molecular Medicine, Faculty of Medicine, Laval University
• Data and machine learning for multi-level risk prediction
  Rumi Chunara – Associate Professor of Biostatistics and Computer Science and Engineering, New York University

Session 4: Heterogeneity in terms of disease susceptibility, progression, resilience, reversibility, and treatment strategy

Co-chairs: William Cefalu and Fei-Fei Liu

• Heterogeneity in diabetes and potential for precision medicine
  Paul Franks – Director, Translational Medicine, Scientific Director in Medical Science, Novo Nordisk Fonden, Professor of Genetic Epidemiology, Lund University
• Heterogeneity in obesity-associated metabolic dysfunction and response to weight loss
  Bettina Mittendorfer – Professor of Medicine and Nutritional Sciences, Washington University
• Heterogeneity of chronic kidney diseases
  Ian de Boer – Professor of Medicine, and Adjunct Professor of Epidemiology, University of Washington
• Heterogeneity in fatty liver disease
  Luca Valenti – Associate Professor, Università degli Studi di Milano
• Microbiota contribution to the heterogeneity of obesity and insulin resistance
  Natalia Shulzhenko – Associate Professor – Immunology, Oregon State University
• Variability in clinical presentation, pathogenesis, and treatment response in inflammatory bowel diseases: Focus on nutrition
  Eytan Wine – Professor of Pediatrics & Physiology, Clinician Scientist and Pediatric Gastroenterologist, University of Alberta
• Metabolic heterogeneity in therapy resistant breast cancers
  Julie St. Pierre – Professor and Director of Metabolomics Core Facility at University of Ottawa
• Heterogeneity in type 2 diabetes
  John Dennis – Senior Independent Research Fellow, University of Exeter

Summary of speaker presentations and panel discussions

Panel discussions were scheduled at the end of each session, providing an opportunity for participants to ask questions about the topic. Emerging themes from the speaker presentations and panel discussions include:

• Paradigm shift
  • There needs to be a cultural change in the scientific community, including funders and reviewers. Heterogeneity should not be considered as “noise” and research questions should be asked differently.
• Diversity
  • It is critical to design research to include populations of non-European ancestry to study heterogeneity, avoid biases and ensure fairness in precision medicine.
  • People come from a mix of genetic ancestry – consider looking at differences in genetics, social experiences, and social and environmental exposures (e.g., stress, trauma, macro-structural policies, etc.).
• Ethical issues / accessibility
  • Precision medicine should be equitable and accessible to all people. There is a danger that high-end technologies may be less accessible to disadvantaged groups.
• Knowledge mobilization
  • Consider how research can be translated into practice – we need to be thinking about this throughout the entire research process and not just at the end.
• Collaboration / interdisciplinarity
  • Consider that heterogeneity comes at many different levels – find a way to integrate various levels of heterogeneity in study design and still understand them individually.
  • Think beyond diseases/organs – look at similar outcomes and work across different disciplines (the prevalence of obesity, non-alcoholic fatty liver disease and hepatocellular carcinoma have similar trajectories).
• Determinants of health
  • “Our past informs our present which then informs our future” – avoid a reductionist approach and incorporate cultural and historical trauma in research.
• Indigenous health
  • Coloniality needs to be dismantled as it is a key driver of health and social inequities for Indigenous Peoples in Canada. Addressing food security and food sovereignty in Indigenous food systems is a way forward.
  • Climate change will exacerbate the challenges faced by Indigenous Communities.
• Better understanding of diseases
  • Using data-driven approaches can provide insights into heterogeneity but the underlying mechanism of diseases is a “black box”.
• Multiple ways of knowing
  • Traditional diet may select against polymorphisms that make you inefficient, highlighting the importance of including dietary patterns in different regions among different populations.

Summary of breakout group discussion

All participants were invited to participate in breakout groups to discuss questions aligned with the workshop objectives. A summary of this discussion can be viewed below:

• Question 1: What do you perceive are the major gaps and opportunities for research in the area of heterogeneity in nutrition and metabolic health?

  Theme	Notes
  Diversity	Canada has a diverse population that can be leveraged for heterogeneity research Heterogeneity within minority subgroups exists and multilayer analyses are needed Data is needed on diverse population subgroups and there is a need to look at disaggregated data and risk factors in sub-groups
  Connection of biological and social-structural determinants	Health promotion and prevention remains a huge gap Understand all levels of heterogeneity from biological level to social-structural-intersectional determinants of health Address psychosocial impacts of chronic disease and its effects on heterogeneity (i.e., how living with disease affects stress, compliance, etc.) Nutrition guidelines are not aligned with individual’s food sources (i.e., does not consider food insecurity)
  Collaboration	Work with researchers across different fields instead of working in silos to determine priority questions, best methods to be used, and appropriate study designs Facilitate collaboration, bring expertise together and exchange knowledge (symposiums / conferences) Cultural change is required to collaborate (pre-register studies, share data, codes, etc.) Collaboration with countries that are ahead in the field (e.g., Europe in terms of electronic medical records [EMR] and biobanks) Investing in cross-institute funding opportunities/collaborative initiatives between CIHR, Social Sciences and Humanities Research Council (SSHRC), and Natural Sciences and Engineering Research Council (NSERC)
  Indigenous health research	More Indigenous-led community-driven health research Consider data sovereignty, ownership and stewardship (Principles of OCAP® - Ownership, Control, Access and Possession) Training in using data and engaging with Indigenous communities (cultural safety, OCAP®, etc.) Build trust and partnerships in Indigenous communities

• Question 2: What are Canada’s particular strengths and barriers that can help or challenge efforts to accelerate research efforts in the area of heterogeneity in nutrition and metabolic health?

  Theme	Notes
  Patient and citizen engagement	Diverse patients and perspectives are needed to help drive research to align health needs and research objectives More community-led and -driven research is needed Need to have citizen partners in addition to patient partners especially for health promotion and prevention Meaningful collaboration with stakeholders in all aspects of research
  Expertise and Resources Required	Establishing capacity of training in data science, analyses, programming, and computational / statistical expertise Build capacity by mentoring and training researchers in the field heterogeneity in nutrition and metabolic health (e.g., Health Research Training Platform Pilot) Development of resources to provide advice and guide researchers in engaging communities
  Knowledge Mobilization	Clear knowledge translation path required for any research including for complex omics Research needs support from the decision makers and regulatory agencies
  Funding	Allow pilot funding to get research started from base research question Funding to access, manage, and analyze cohorts and biobanks is a challenge (e.g., could resemble UK biobank structure) Support development of platforms and ongoing research to reduce costs Relationship building takes time and are not aligned with funding cycles

• Question 3: Are there promising new research opportunities or “low-hanging fruit” that could be addressed/advanced in the shorter term to further understand heterogeneity in terms of disease susceptibility, progression, resilience, reversibility and treatment strategies?

  Theme	Notes
  Study Design	More longitudinal and intra-patient studies to see how much their profiles change overtime Recalling people who have already participated in genetic research (“Recall by genotype” design) Gene expression - biopsies are a downside, there may be new less invasive methods of collecting samples Ensure research is representative of population in terms of heterogeneity High resolution data and larger sample sizes are required including for machine learning Well-designed intervention studies that are outcome driven taking into account genetics, lifespan, etc. Heterogeneity needs to be considered in all aspects of research Consider using routine clinical information initially as omics research can be complex and costly Use of new technologies as well as portable devices (i.e., NutriPhone) to identify molecular signature of disease, record and quantify dietary intake, monitor lifestyle and exposure, etc.
  Leveraging existing resources	Integration of data (i.e., linkages to electronic medical records and non-conventional dataset [e.g., Agriculture Canada, Nielsen, etc.], incorporation of wearable technology with EMRs, etc.) Collaborate with other researchers and leverage datasets already available (e.g., Canadian Community Health Survey [CCHS], Canadian Health Measures Survey [CHMS], and existing genome-wide association studies [GWAS], biobanks, cohorts, structural-social database, etc.) rather than collecting new samples Standardizing of protocols / harmonizing data collection in surveys, questionnaires, biobanks, cohorts, etc. Awareness of what others are studying in their respective fields and what resources/data on heterogeneity are available Creation of a central database that includes existing biobanks, clinical databases, and expertise of various researchers could lead to more optimal use of these resources.

• Question 4: What are some of the key ethnocultural, ethical, legal, social, and/or privacy considerations that must be incorporated into new research that aims to understand and address heterogeneity?

  Theme	Notes
  Ethical/accessibility	Expensive technology (e.g., omics) need to be accessible to all and utilized in a way that won’t further amplify disparities Consider treatment availability when diagnosing patients at risk
  Privacy/legal	Privacy / security concerns with device monitoring, genetic testing, and data stored in cloud (e.g., for glucose monitoring – insurance companies might raise rates if patient data is shared) More open access and timely research data
  Ethnocultural	It is difficult to recruit underrepresented populations – consider investing time needed to build relationships in the community Focus efforts on populations previously excluded because of systemic barriers, etc. Understand how differences in cultures and beliefs affect disease prevention, treatment and management

Conclusion

CIHR-INMD is grateful to the members of the planning committee (see Appendix 1) for their contributions to organizing this workshop, and all our speakers and moderators for their willingness to share their research and experience. The discussion in this workshop will inform new research opportunities and approaches to understanding heterogeneity in nutrition and metabolic health and how this may lead to more effective ways to intervene, prevent, reverse, and treat disease.

For more information

If you require a copy of the workshop notes and breakout room discussions, please email Frank Ong at frank.ong@sickkids.ca.

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Appendix 1: Planning Committee

Date modified:

2023-01-24