By: Johnny Kung
4 May, 2020
Research on the human microbiome is evolving at a rapid pace, disrupting our understanding of healthy development and aging. Knowing how the human microbiome is impacted by factors such as environment, nutrition, and cultural practices will be important to ensuring the effective delivery of evidence-based public health practices. Educating the next generation of health practitioners on this new knowledge will therefore be essential.
On March 11, 2020, CIFAR convened a virtual roundtable that brought together Fellows from CIFAR’s Humans & the Microbiome research program with senior leaders at Canadian and US schools of public health. Through short presentations and facilitated discussion, researchers and public health leaders shared perspectives on the relevance of the microbiome to public health, and explored actionable and collaborative opportunities for integrating microbiome knowledge into public health curricula.
Key Insights
The microbiome forms an “inner ecosystem” in our bodies, with at least as many microbial cells as human cells and possibly 100 times more microbial genes than human genes. Unlike our own genome, which changes in its expression level but basically does not change in its contents throughout our lives, the microbiome is dynamic and changes over time as well as with environmental and behavioural factors such as diet and antibiotics use.
Babies are basically born sterile, so they obtain their microbiome through three main ways: while passing through the birth canal, from breast milk, and from the environment after birth. Statistics show that more than a third of infants in the United States are born by caesarian section, a third of mothers and infants in North America now take antibiotics during the first year after birth, and more than 50% of babies are fed some formula milk by two weeks after birth. All of these factors affect children’s gut microbial diversity, with possible implications for the risk of developing chronic diseases such as asthma, allergy and obesity.
Compared to formula milk, breast milk contains additional components such as hormones, growth factors, as well as probiotics (live beneficial bacteria) and prebiotics (small carbohydrates that cannot be digested by humans but important for bacterial growth). The prebiotics composition in breast milk varies significantly among individuals, with some variation correlating with genetic differences, seasonal variation and pregnancy order, and can perhaps be seen as a “personalized medicine” for infants during a time when their gene expression is being fine tuned.
As an individual grows from infancy to adulthood, the microbiome experiences less stochastic week-to-week changes and becomes more diverse, with a balance between beneficial (symbiont) and harmful (pathobiont) microbes. However, as one ages, the microbiome diversity once again becomes more stochastic and can experience imbalance (dysbiosis) between symbionts and pathobionts. This is partly due to higher permeability of the gut and gums, where the mucus layer breaks down and microbes can cross into the body. The increased number of pathobiont microbes can exacerbate chronic, low-grade inflammation that is linked to diseases and aging (inflammaging).
Recent studies suggest important roles for microbes in a number of age-related diseases. For example, bacterial metabolism of choline in red meat into trimethylamine, which is then metabolized by the liver into trimethylamine N-oxide (TMAO), seems to be important for the development of cardiovascular diseases such as atherosclerosis and stroke. Neurodegenerative diseases also seem to be affected by the microbiome – there is evidence that dysbiosis in the gut can predict incidence of Parkinson’s, and severing the vagus nerve between the gut and the brain seems to protect against the disease; while there is some suggestion that oral hygiene is linked to Alzheimer’s disease. Together, there is evidence to suggest that “non-communicable” chronic diseases could in fact be communicable in some contexts through social interactions, although much more research is needed.
There is good evidence that the microbiome is one pathway that mediates some of the effects of social and environmental factors on health, and thus can also be a pathway for health intervention. Understanding the microbiome’s role can have implications for public health policies, e.g., regarding school recesses (is the outdoor environment, with higher microbiome diversity, important in addition to the physical exercises?) and breastfeeding (if the microbes in breast milk are important, could storage or freezing of the milk make a difference?). The observed health effects of certain policy changes, such as the declining level of childhood asthma in jurisdictions that are seeing decreased antibiotics use, may provide additional support.
The mechanistic basis of a lot of observed microbiome effects or correlations is not yet known, pointing to research gaps as well as the need to avoid hyping the health benefits of microbiome-based interventions. For example, transient microbiome changes may be “drivers” that get locked in by longer term immune changes, or microbiome changes may simply be “passengers” of other environmental or physiological changes. More research will be needed to elucidate any causal relationships.
For epidemiological cohort studies looking at the connection between microbiome and health outcomes, it is important to note any unmeasured confounders, including those introduced by a lack of diversity (socioeconomic, geographic, ethnic) in the study populations. Newer studies are making an attempt to address such diversity issues.
For epidemiological cohort studies looking at the connection between microbiome and health outcomes, it is important to note any unmeasured confounders, including those introduced by a lack of diversity (socioeconomic, geographic, ethnic) in the study populations. Newer studies are making an attempt to address such diversity issues.
Priorities and Next Steps
A microbiome-informed perspective may be important for public health practice in a number of ways. It can help reinforce a “one health” notion that takes into account diverse factors such as nutrition, exercise, antibiotics, wound care, oral hygiene and reproductive health. It might promote a more ecological lens rather than a militaristic, hygiene-focused “destroy all microbes” messaging. It can help practitioners assess the benefits and harms of public health interventions (e.g., iron fortification for infants in developing countries can lead to risk of diarrhoea for some due to interactions with the microbiome). And it may alert us to the limitation of risk-factor epidemiology, when treating one disease (e.g., targeting H. pylori with antibiotics to treat peptic ulcers) may lead to adverse health outcomes (loss of possible protective effects of H. pylori).
To incorporate insights from microbiome research into public health curricula, researchers and practitioners need to decide on thresholds of evidence strength, relevance and usefulness. Training for public health practitioners must also continue to emphasize the role of uncertainty in scientific evidence, the importance of critical thinking about different levels of evidence and tradeoffs, and when and how to act given limited evidence.
Having clearly defined goal(s) for integrating microbiome research insights into public health curricula is important and can influence decisions about what information to include, where in the curriculum to include the information, and which faculty members should be involved. These goals may include:
Informing public health actions (in which case much of the evidence may still be too preliminary);
Helping practitioners better communicate with the public in terms of addressing hype and handling seemingly mixed messages (e.g., balancing personal hygiene with getting exposed to diverse microbes);
Increasing practitioners’ awareness about the potential roles of microbes in the complex aetiology of diseases; and/or,
Spurring collaboration between microbiome research and public health to establish criteria for evaluating evidence or to take the microbiome into account when conducting epidemiological studies.
Researchers and educators need to devise and pilot ways to incorporate microbiome research insights into already-packed public health curricula, where the instructors may not always have the expertise to feel comfortable teaching the materials. One approach is to use “lego blocks” – prepackaged modules consisting of short lectures, skills labs, Q&A’s, etc., each relating to specific public health issues (such as child health, built environment, or the community microbiome), which can be used standalone or assembled into different combinations. Creating, testing and updating such course modules will require an advisory group of researchers and practitioners, as well as a number of institutions willing to pilot the modules
Different schools face different challenges and opportunities in integrating microbiome insights into public health curricula, e.g., smaller institutions (with limited resources and few faculty members with the necessary expertise, but more centralized and able to integrate the materials into multiple foundational courses) vs. larger schools (more decentralized and have more flexibility in building new, elective courses from the ground up, but harder to get the content into core courses required for all students). It will be instructive to learn from and leverage existing efforts spearheaded by some researchers at their local institutions.
Round Table Participants
Katherine Amato, Assistant Professor, Northwestern University / Fellow, Humans & the Microbiome program, CIFAR
Meghan Azad, Assistant Professor and Canada Research Chair in Developmental Origins of Chronic Disease, University of Manitoba / Fellow, Humans & the Microbiome program, CIFAR
Emily Barrett, Associate Professor, Rutgers School of Public Health
Peter Berman, Professor and Director of the School of Population and Public Health, University of British Columbia
Eran Elinav, Professor, Weizmann Institute of Science / Fellow, Humans & the Microbiome program, CIFAR
Naama Geva-Zatorsky, Assistant Professor, Technion / Global Scholar, Humans & the Microbiome program, CIFAR
Philippe Gros, Professor, McGill University / Fellow, Humans & the Microbiome program, CIFAR
Curtis Huttenhower, Professor of Computational Biology and Bioinformatics, Harvard T.H Chan School of Public Health
Ellen MacEachen, Associate Professor and Associate Director of Graduate Research Programs, University of Waterloo School of Public Health and Health Systems
Melissa Melby, Associate Professor, University of Delaware / Co-Director, Humans & the Microbiome program, CIFAR
Mark Nichter, Regents’ Professor, University of Arizona / Advisor, Humans & the Microbiome program, CIFAR
Heather Orpana, Senior Research Scientist, Public Health Agency of Canada
Elizabeth Sanders, Assistant Professor, University of Toronto Dalla Lana School of Public Health
Brenda Wilson, Professor and Associate Dean, Memorial University
Liping Zhao, Eveleigh-Fenton Chair of Applied Microbiology, Rutgers School of Environmental and Biological Sciences / Fellow, Humans & the Microbiome program, CIFAR
CIFAR is a registered charitable organization supported by the governments of Canada, Alberta and Quebec, as well as foundations, individuals, corporations and Canadian and international partner organizations.
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