Current Environmental Health Reports

https://doi.org/10.1007/s40572-018-0191-2

FOOD, HEALTH, AND THE ENVIRONMENT (KE NACHMAN AND D LOVE, SECTION EDITORS)

An Integrated Socio-Environmental Model of Health and Well-Being:

a Conceptual Framework Exploring the Joint Contribution
of Environmental and Social Exposures to Health and Disease Over
the Life Span
Hector A. Olvera Alvarez 1 & Allison A. Appleton 2 & Christina H. Fuller 3 & Annie Belcourt 4 & Laura D. Kubzansky 5

# Springer International Publishing AG, part of Springer Nature 2018

Abstract
Purpose of the review Environmental and social determinants of health often co-occur, particularly among socially disadvan-
taged populations, yet because they are usually studied separately, their joint effects on health are likely underestimated. Building
on converging bodies of literature, we delineate a conceptual framework to address these issues.
Recent findings Previous models provided a foundation for study in this area, and generated research pointing to additional
important issues. These include a stronger focus on biobehavioral pathways, both positive and adverse health outcomes, and
intergenerational effects. To accommodate the expanded set of issues, we put forward the Integrated Socio-Environmental Model
of Health and Well-Being (ISEM), which examines how social and environmental factors combine and potentially interact, via
multi-factorial pathways, to affect health and well-being over the life span. We then provide applied examples including the study
of how food environments affect dietary behavior.
Summary The ISEM provides a comprehensive, theoretically informed framework to guide future research on the joint contri-
bution of social and environmental factors to health and well-being across the life span.

Keywords Total environment . Social determinants . Cumulative exposures . Life course . Health disparities

Introduction crossover despite a common goal of promoting and

safeguarding human health. Social and environmental risks do
Researchers evaluating social and environmental determinants not exist in isolation but rather co-occur and disproportionately
of disease have historically worked in parallel with little affect socially disadvantaged individuals and populations

Hector A. Olvera Alvarez and Allison Appleton are co-leading authors.

This article is part of the Topical Collection on Food, Health, and the
Environment

* Hector A. Olvera Alvarez 1

School of Nursing, University of Texas El Paso, 500 W. University
holvera@utep.edu Ave, El Paso, TX 79968, USA
2
School of Public Health, Department of Epidemiology and
Allison A. Appleton Biostatistics, University at Albany, 1 University Place,
aappleton@albany.edu Rensselaer, NY 12144, USA
3
School of Public Health, Division of Environmental Health, Georgia
Christina H. Fuller
State University, P.O. Box 3995, Atlanta, GA 30302, USA
cfuller@gsu.edu
4
School of Community and Public Health Sciences/Pharmacy
Annie Belcourt Practice, University of Montana, 32 Campus Drive,
annie.belcourt@mso.umt.edu Missoula, MT 59812, USA
5
Department of Social and Behavioral Sciences, Harvard T.H. Chan
Laura D. Kubzansky School of Public Health, 677 Huntington Avenue,
lkubzans@hsph.harvard.edu Boston, MA 02115, USA

experiencing health disparities. As such, traditional siloed re-
search likely underestimates or misidentifies the joint complex
effects of social and environmental exposures on health. As
social and environmental exposures may have synergistic
health effects that accumulate and drive disparities over the life
span (from conception to death) [1, 2], major granting and
professional organizations like the National Institute of
Environmental Health Sciences and the Environmental
Protection Agency are increasingly calling for research and
services that jointly address the health consequences of social
and environmental exposures [3, 4]. This emergent interdisci-
plinary research approach focuses on the totality of factors with-
in the environment that impact health. This includes conceptu-
alizing not only social and environmental factors that increase
risk but also factors that are protective, and focusing on both
disease and healthy states. Moreover, identifying mechanisms
through which these processes affect health over the life span is
critical for recognizing opportunities for intervention during
potential sensitive periods. To promote this perspective, we
have developed a conceptual model we refer to as the
Integrated Socio-Environmental Model of Health and
Well-being (ISEM). The model examines how environmental
and social factors may jointly contribute to health and well-being
across the life span. It is designed to have broad applicability
across populations and life stages, and to facilitate the study of
biologic and behavioral mechanisms linking exposures to dis-
ease and health disparities, while explicitly considering the role
of positive factors in promoting health and well-being.
Here, we identify the components of ISEM, while also
reviewing prior frameworks and empirical evidence that in-
formed the development of this model. Next, we illustrate
how ISEM might guide research on how food environments
affect dietary behavior, and further provide two additional ex-
amples of how ISEM can guide the integrated study of social
and environmental factors across a range of health problems.
We conclude by discussing the limitations of the ISEM and
identifying needs and priorities for future research in this area.
Previous Models and Frameworks
A number of conceptual frameworks and models describe
how environmental (e.g., air pollution, access to parks, cli-
mate change) [5, 6] or social (e.g., early-life adversity, harsh
family conditions) [7•, 8] factors independently affect physical
and/or mental health outcomes [1, 9]. These frameworks often
provide detailed descriptions of the pathophysiologic or so-
ciocultural pathways through which each factor impacts
health. However, the co-occurrence and potential interactions
between environmental and social factors have received less
attention. Other frameworks have explicitly considered the
totality of environmental exposures via perspectives described
as total environment, cumulative risk, and the exposome [1,
Curr Envir Health Rpt
10••, 11••]. These perspectives share key attributes in that they
consider multiple exposures simultaneously, incorporate both
physical and social factors, and often seek to describe health
disparity-related processes [12–15].
Two of these perspectives have been particularly influential
to the development of ISEM. Both focus specifically on child
and maternal health [10••, 11••]. Morello-Frosch and Shenassa
(2006) proposed a model of how place-based stressors (e.g.,
poverty, low social capital) increase an individual’s susceptibil-
ity to environmental pollutants and adversely impact maternal
and child health outcomes [10••]. The model explicitly con-
siders multi-level interactions between community- and
individual-level stressors and buffers, and outlines a mechanis-
tic pathway linking exposure to environmental pollutants to
adverse health outcomes. Clougherty and Kubzansky (2009)
drew on this model to further delineate pathways through which
combined exposure to air pollution and psychosocial stress
might affect respiratory health [16•]. In contrast, a model pro-
posed by Tulve and colleagues [11••] takes a more
system-based approach to describe child health as the result of
intrinsic biological factors, activities and behavior, and expo-
sure to social and environmental factors. This model provides a
total environment perspective that encompasses both the phys-
ical and social environments, defines chemical and
non-chemical stressors, and integrates proximal and distal ef-
fects across time (life course) and space (e.g., individual, com-
munity), but has less focus on underlying mechanisms.
Research in this emergent field has grown to encompass
more complex pathways, interactions between multiple expo-
sures, cultural factors, resources and susceptibilities occurring
at the individual and community level, positive and adverse
health outcomes, and differences in effects across the life
course. Existing frameworks may not accommodate this ex-
panded set of issues because they do not capture one or more
of following domains: (a) clear testable mechanistic pathways,
(b) multiple pathways through which social and environmen-
tal factors could interact, (c) behavioral pathways, (d) positive
health outcomes or potential health-promoting factors, and (e)
potential intergenerational transmission of effects. The ISEM
was developed drawing on insights of earlier models, with the
purpose of expanding applicability to many populations and
contexts.
The Integrated Socio-Environmental Model
of Health and Well-Being
Model Overview
The ISEM was developed through a yearlong series of meet-
ings and discussions among an interdisciplinary team of envi-
ronmental health scientists, epidemiologists, and social scien-
tists; collaborative activities to develop the model were
Curr Envir Health Rpt
supported by the Harvard JPB Environmental Health
Fellowship Program, an interdisciplinary program for re-
searchers working at the intersection of environmental and
social determinants of health. The team reviewed prior con-
ceptual models and framework papers, conducted literature
reviews, and identified gaps in the evidence base to develop
the model. A preliminary version of the ISEM was presented
at a JPB Fellowship supported workshop titled “What is the
joint contribution of environmental and social determinants of
health in explaining health and disease over the life course?
Building the field and identifying research priorities”
(October 2017; Saratoga Springs, NY). The model was re-
vised according to feedback provided by workshop attendees,
which included experts in fields such as social epidemiology,
environmental health, epigenetics, and exposure science.
The ISEM illustrates how environmental and social factors
combine and potentially interact, via multi-directional path-
ways, to affect health and well-being over the life span and
across generations (Fig. 1). The ISEM starts by characterizing
individuals via intra-individual factors (e.g., sex, age) and as
part of a community which is further embedded in a larger
social and physical environment shaped by both policy and
culture. Communities are comprised of culturally based norms
and practices that can shape and be shaped by the larger social
and environmental contexts. Thus, intra-individual,
community-level, social, and physical environmental factors
independently and jointly play a role in the health of individ-
uals. At any given moment, individuals are both exposed and
responding to an array of interrelated physical environmental
factors (e.g., natural, built) and social-structural factors (e.g.,
race, socioeconomic position). These factors in turn jointly or
independently influence biologic (e.g., inflammation) and
Fig. 1 The Integrated Socio-Environmental Model of Health and Well-being (ISEM)
behavioral (e.g., diet) responses that ultimately drive health
or disease. Furthermore, biologic and behavioral responses
to exposures can be independent or may also be interrelated.
Resources and susceptibilities, produced either by intrinsic or
extrinsic factors, can shape biologic and behavioral responses
and mediate and/or modulate effects of social and physical en-
vironmental factors on health. Adding complexity, these re-
sources and susceptibilities are also patterned by physical and
social environmental factors at individual and community
levels. For example, accessibility and availability of healthy
food may be more limited in lower- versus higher-income com-
munities which in turn affects dietary behaviors with down-
stream implications for health. Overtime, interactions between
access and behaviors involved in diet and nutrition can influ-
ence the cultural practices of a community. One example, from
the experience of indigenous communities, stems from the in-
troduction of the Food Distribution Program on Indian
Reservations authorized under Section 4(b) of the Food and
Nutrition Act of 2008 and Section 4(a) of the Agriculture and
Consumer Protection Act of 1973. These foods tended to be of
lower nutritional quality (high in carbohydrates, fat, and sugar).
Foods made from these products have since come to be viewed
as traditional foods, thereby adding to the complex set of risk
factors facing many Native communities.
In addition, ISEM explicitly notes that biological and behav-
ioral responses can have either adverse effects and contribute to
disease onset and ill being, or protective effects and contribute
to positive health and well-being. Finally, ISEM recognizes that
exposures and outcomes may be connected by dynamic pro-
cesses that are evident at and continually operate across all life
stages and may transcend generations. Model components are
described in detail in the following sections.

Model Components
The Total Environment
The ISEM adopts a total environmental perspective and brings
a sharp focus on how individuals are embedded within com-
munities and what aspects of these communities may be useful
to consider in more detail [11••]. The model further notes that
culture wraps around all aspects of the environment and often
provides the lens through which policies and experiences are
interpreted. Culture refers to collectively held behavioral
norms, traditions, worldviews, and beliefs, which may shape
socio-environmental factors and their health effects in system-
atic ways. Culture can shape the ways communities view
causes of health problems as well as potential solutions [17].
Cultural factors are perhaps the least well studied in this arena,
but represent a unique source of either strength or potential
susceptibilities within communities and individuals [18].
The ISEM also distinguishes the physical and social envi-
ronments, and further subdivides the physical environment
into two domains, natural and built. We define the physical
environment as constructed foundational, chemical, and bio-
logical stressors that emerge from both built (i.e., anthropo-
genic) and natural processes. A wide range of factors that
emerge from the built environment, such as air pollution, have
been linked to adverse health outcomes including cardiovas-
cular disease (CVD), respiratory disease, and mortality [19,
20]. Stressors originating from the natural environment have
been less well studied, but are also important [21, 22]. For
example, extreme heat events are associated with increases
in mortality and there appear to be regional differences, with
stronger effects seen in low-income areas [23, 24].
The social environment encompasses those determinants
tied to collective human interactions and activities that influ-
ence health through culture, norms, and controls [25, 26]. The
social environment is shaped by social structures that impact
resource distribution and allocation within a society, which in
turn pattern exposure to stressors or protective factors. Perhaps
one of the best studied structural factors is a person’s position in
the social hierarchy, typically referred as socioeconomic posi-
tion (SEP) [27, 28]. Lower SEP has been linked to adverse
outcomes including reduced life expectancy as well as higher
incidence of many chronic conditions, such as cancer, respira-
tory disease, and CVD [26]. Another common social environ-
mental exposure is psychosocial stress, which has been inde-
pendently associated with adverse outcomes such as depres-
sion, CVD, and life expectancy [29–31]. Psychosocial stress
results when external conditions overwhelm an individual’s
capacity to manage negative effects of external stressors [31].
Other social environmental exposures include factors like in-
come distribution, social capital, and discrimination.
Finally, the ISEM explicitly recognizes that policy shapes
various aspects of both the social and physical environment
Curr Envir Health Rpt
and provides a context in which the downstream components
of the model take place. For example, neighborhood zoning
policy could directly affect the density of alcohol outlets,
availability of grocery stores, and access to safe and affordable
housing in communities, which may in turn drive
individual-level behaviors and subsequent health outcomes.
Resources and Susceptibilities
We define resources as factors (e.g., biological, sociocultural,
emotional, and economic) that help individuals adaptively
cope with socio-environmental challenges, and define suscep-
tibilities as factors that impair individuals’ ability to cope
adaptively. Resources and susceptibilities may be shaped by
aspects of the total environment (e.g., SEP, climate, and cul-
ture) and can be identified at the individual and community
levels. Resources may be considered protective and restor-
ative factors and susceptibilities as risk-inducing factors.
Accordingly, resources and susceptibilities can mediate or
modulate biological and behavioral responses to physical
and social environmental exposures and ultimately their effect
on health and well-being.
In addition, resources and susceptibilities may be either
intrinsic to the individual or extrinsic. Examples of intrinsic
factors include genetic susceptibilities, mental health factors,
and cognitive and psychological abilities. Examples of extrin-
sic factors include differential exposures to biological toxins,
chemical pollutants, social support, or stigma. Resource and
susceptibility factors may modulate effects of
socio-environmental exposures by altering the magnitude
and trajectory of biologic and behavioral responses to expo-
sures. For instance, an intrinsic factor like genetic propensity
for certain diseases can amplify the adverse effect of a psy-
chosocial stressor (e.g., financial stress) on health, while an-
other intrinsic factor, effective stress coping skills, could pro-
tect against it [32]. Similarly, an extrinsic factor like social
support may mitigate adverse effects of the built environment,
for example, protecting against exposure to food deserts (low
availability to healthy foods) by providing the means (e.g.,
transportation) to access healthy foods, reducing the risk of
obesity, and the sequelae of health problems [33].
Biologic and Behavioral Responses
Numerous biologic processes and behaviors are sensitive to
social and environmental exposures, and in turn contribute to
health. We define response as any behavioral or biologic al-
teration that is attributable to upstream exposures and stimuli,
and which may function as a mechanism linking exposures to
health outcomes. Following this broad definition, many bio-
logic processes are candidates. For example, elevated blood
pressure may occur in response to higher levels of perceived
stress and also to air pollution exposure, and these joint effects
Curr Envir Health Rpt
in turn contribute to hypertensive disease [34, 35]. Numerous
other processes, including inflammation, alterations to the epi-
genome, and microbiome composition, have been identified
as potential mechanisms [36]. Likewise, numerous health be-
haviors such as smoking, diet, and physical activity may be
responses to socio-environmental stimuli and thus may lie on
the pathway linking socio-environmental exposures and
health outcomes. For example, environmental (e.g., availabil-
ity and accessibility of supermarkets) and social (e.g., SEP)
factors might jointly influence intake of healthy fruits and
vegetables, and thereby contribute to disease risk [37–41].
Health and Well-Being Versus Disease and Ill-Being
ISEM posits that both positive and negative health outcomes
are a product of the interactions between socio-environmental
factors. The model goes beyond a deficit and disease-based
approach to health to consider positive health outcomes and
provides a framework for identifying not only risk but also
protective, restorative, and health-promoting factors.
Applications of ISEM
Identifying Novel Pathways
The ISEM can facilitate the identification of novel pathways for
exploration by providing a broad scope as well as an emphasis
on mechanisms underlying the synergistic effects of the social
and physical environment on health. Critical to note is that more
detailed and fine-grained aspects of the ISEM, such as feedback
loops between various systems or specific bio-behavioral pro-
cesses, were purposely left out to allow for the key model
elements to be presented in a clear and parsimonious way. In
this regard, the ISEM is intended to serve as a framework from
which more detailed models can be derived. For example, the
model promotes consideration of behavioral and biological re-
sponses along with resources and susceptibilities, thereby sig-
naling the critical importance of delineating underlying mech-
anisms. However, detailed discussion of mechanisms would
more likely be available in models inspired by ISEM, but spe-
cific to a particular research question. Here, we consider exam-
ples of two mechanisms that can be explored with the ISEM,
epigenetics, and the microbiome.
Epigenetics
The burgeoning field of epigenetics indicates that the switches
on our genes are heavily influenced by social and environmental
exposures and the resulting pattern in gene expression can in turn
affect health outcomes. The sensitivity of the epigenome is per-
haps greatest during fetal development, with evidence rapidly
accumulating that environmental and social exposures can
modulate the epigenome and influence later health. For example,
several epigenome-wide association studies have linked prenatal
exposure to neurotoxic metals (e.g., arsenic, mercury) to meth-
ylation across a number of loci [42–46], including sites related to
central nervous system development and behavioral disorders
[47, 48]. Other work has linked methylation at these sites to
adverse child neurodevelopment [48] and lower birthweight
[47], both considered sentinels of cognitive-behavioral problems
and later life health [49, 50]. Likewise, studies have found
that depression and related markers of social adversity dur-
ing pregnancy contribute to epigenome-wide DNA meth-
ylation [51], and in particular to genes involved in the
hypothalamic-pituitary-adrenal (HPA) axis [52–56], which regu-
lates the body’s response to stress. Such gestational HPA-related
epigenetic changes are associated with restricted fetal growth
[57], and contribute to poor neurodevelopment and dysregulation
of the child’s stress response systems [56, 58–62]. Although
studies rarely consider combined effects of social and environ-
mental exposures on the epigenome, taken together, these paral-
lel lines of research highlight the epigenome’s sensitivity to both
social and environmental exposures and suggest that epigenetics
may provide a fruitful avenue for research on the joint effects of
these exposures to lifelong health.
Microbiome
The human microbiome, which comprises all microorganisms
(e.g., bacteria, archaea, and fungi) found in human tissues and
biofluids, is shaped by social and environmental factors. The
microbiome plays an integral role in optimal human health.
Dysbiosis, meaning microbial imbalance or maladaptation,
affects host immunity [63] and has been associated with the
pathology of several illnesses including asthma [64, 65], in-
flammatory bowel disease [66], multiple sclerosis [67], anxi-
ety [68], and depression [69]. The composition of the
microbiome is shaped by exposures at multiple levels, includ-
ing individual-level diet or medication use, as well as psycho-
social factors (e.g., psychological stress, social interactions)
[70–73]. Moreover, composition and diversity of the gut mi-
crobiota also vary according to aspects of the social and phys-
ical environment such as ethnicity and geographical location,
partially due to dietary customs (i.e., an aspect of the socio-
cultural environment) and food availability (i.e., and aspect of
the natural environment), and to other environmental expo-
sures (e.g., heavy metals) [74–76]. These variations have in
turn been linked with health outcomes. For instance, among
populations with Western diets (e.g., high in animal protein,
sugar, fat), a depleted microbial diversity in the gut has been
linked to rising incidence of obesity, coronary heart disease,
metabolic syndrome, and certain types of cancer [72].
Conversely, gut microbes can have protective properties by
modulating human toxicity of environmental pollutants via
metabolic processes [71]. Taken together, these findings

suggest that the microbiome may serve as a critical pathway
connecting joint exposure to socio-environmental factors to
health and well-being.
Identifying Joint Contributions of Multiple Aspects
of the Total Environment: Guiding Diverse Research
Questions
Research guided by ISEM would start with the premise that
both social and environmental factors matter, and considering
effects of these factors in combination is likely to be fruitful.
Here, we consider how the model might guide research aimed
at understanding how social and environmental factors might
jointly influence diet and obesity; we then provide two addi-
tional examples of research questions ISEM might inform.
Example 1—Food Environment, Dietary Behavior,
and Obesity
Investigators seeking to understand the role of the environment
in risk of obesity have identified the food environment as critical.
Research has consistently demonstrated that a poor neighbor-
hood food environment (defined according to level of availabil-
ity and accessibility to healthy food [77]) as well as the quality of
food are significant risk factors for obesity [41, 78]. In contrast,
greater availability of and accessibility to supermarkets and
higher quality of foods are associated with higher consumption
of fruits and vegetables and overall healthier diets [79, 80].
However, recent reviews suggest that effects of the food envi-
ronment on obesity risk are mixed or have effects that are rela-
tively small in magnitude [81]. The ISEM framework suggests
that considering the food environment in isolation as a risk factor
for poor dietary behaviors and obesity may be insufficient.
Other work has demonstrated that a variety of other up-
stream social structural factors influence the food environment
and subsequent dietary behaviors [79, 82]. For example,
low-income and racial/ethnic minority groups are more likely
to be exposed to poor food environments characterized by an
increased availability and accessibility to fast-food restaurants
and convenience stores [83, 84], whereas individuals living in
higher-income neighborhoods have increased availability and
access to supermarkets and grocery stores [80, 83, 85].
Moreover, psychosocial resources and susceptibilities that are
patterned according to race/ethnicity and SES may modulate
effects of food environmental exposures on dietary behaviors,
which in turn influence obesity risk. For example, psychosocial
stress and depression are more prevalent among those with low
SES [86], and these experiences are also associated with greater
consumption of unhealthy foods and obesity [87–89]. Thus,
individuals with low SES may experience the “double jeopar-
dy” of being more prone to consume more unhealthy foods as
well as having less access to healthy food. Absent considering
these modulating factors, the role of the larger environment in
Curr Envir Health Rpt
obesity risk may be under-appreciated. The ISEM framework
can encourage examination of the multilevel determinants,
moderators, and pathways through which the food environment
increases the risk of obesity.
Example 2—Childhood Adversity, Inflammatory Pathways,
and Vulnerability to Air Pollution Exposure
Some investigators have recently hypothesized that severe stress
exposure early in life promotes a pro-inflammatory phenotype
(PIP) that heightens individuals’ reactivity and responsiveness to
factors that upregulate inflammation [90••]. The ISEM promotes
consideration of how these kinds of toxic early life social expo-
sures might interact with other environmental exposures to exac-
erbate risk of chronic disease later in life. Thus, early life stress
might promote a PIP, which then increases vulnerability to other
exposures that can separately induce inflammation, a major risk
factor for numerous chronic diseases, including asthma, cardio-
vascular disease, depression, and certain types of cancer.
Across their life span, socially disadvantaged individuals are
disproportionately more likely to experience severe psychoso-
cial stress, and are also more likely to live in environments with
more air pollution. Both psychosocial stress and air pollution
have been linked to chronically elevated inflammation. For
example, in an observational study with healthy adults, expo-
sure to chronic stress was associated with increased expression
of NF-κB and glucocorticoid receptor-β [91]. Likewise, toxi-
cologic work mostly in animals has shown that the inflamma-
tory response to air pollution is mediated by the activation of
NF-κB via oxidative stress [92, 93]. Studies in both humans
and animals have demonstrated that increased expression of
glucocorticoid receptor-β can lead to cellular insensitivity to
glucocorticoids, including in airway cells, creating a physiolog-
ic environment that favors the production of pro-inflammatory
cytokines and increases systemic inflammation [94, 95]. Taken
together, this work suggests that children who are exposed to
high levels of early life stress may be more likely to have in-
creased expression of NF-κB as well as glucocorticoid
receptor-β and a propensity to produce pro-inflammatory cyto-
kines, which could in turn potentiate a subsequent inflammato-
ry response to air pollution [93]. The ISEM framework may
suggest important next steps for testing this hypothesis; for
instance, investigators might consider whether children who
experience early adversity and exhibit epigenetic modulation
also appear to be more susceptible to developing higher levels
of chronic inflammation after exposure to air pollution.
Example 3—Indoor Pollution and Health Disparities
Among American Indian and Alaska Native Communities
Guided by ISEM, research seeking to identify factors that either
potentiate or buffer health risks associated with toxic environmen-
tal exposures might start with an explicit consideration of
Curr Envir Health Rpt
community; this perspective may provide novel insights into the
myriad pathways by which social disadvantage may influence
population health. For example, American Indian and Alaska
Native (AIAN) populations experience disproportionate health ef-
fects of social disadvantage [96–99]. Numerous studies have also
documented that AIAN communities are highly exposed to multi-
ple stressors within cultural (e.g., high levels of discrimination),
environmental (e.g., high levels of indoor pollution), and psycho-
social (e.g., high levels of unemployment) domains [9, 100–105].
The ISEM might suggest considering cultural and social
factors as moderating factors that increase risk of adverse health
outcomes within AIAN populations [106, 107]. For example,
previous research has identified elevated indoor PM2.5 concen-
trations in AIAN communities [108, 109]. A number of cultural
and social factors contribute to sustaining high levels of indoor
air pollution in AIAN and rural communities including the use
of woodstoves to heat homes [108, 110, 111]. Severe economic
limitations and geographic location often limit members of the
AIAN community access to electricity or natural gas as does
geographic location (many AIAN communities live in colder
regions). Traditional cultural (ceremonial use of wood stoves or
plant medicinals) and other economic (in rural communities, it
can be less expensive to gather wood than pay for electricity
and natural gas) factors are also at play. Further contributing to
indoor air pollution among AIAN is the high prevalence of
smoking commercial forms of tobacco. Cultural and ceremoni-
al uses of tobacco likely shaped current social norms around
tobacco, which in turn resulted in less restrictive policies (e.g.,
smoke-free policies), as compared to other communities.
Finally, other historical traditions in many tribal communities
include burning certain plants for ceremonial and spiritual pur-
poses that can also increase indoor air pollution.
The ISEM model suggests that considering potential synergis-
tic effects of these community-related factors may provide addi-
tional insight into effects on health and potential interventions to
mitigate these exposures. Some AIAN community research col-
laborations have started working to promote best burn practices,
use of indoor air filtration units, and implementation of commer-
cial tobacco cessation projects and policies, while still recogniz-
ing the importance of continuing spiritual traditions [108, 111].
However, as suggested by the ISEM model, more factors may be
at play. For example, given high levels of social stress in these
communities, the role of various forms of stress (e.g., experiences
of discrimination, psychological distress, or social support) in
maintaining or changing practices that influence indoor air qual-
ity and the health sequelae may be worth a closer look.
Next Steps and Future Directions
One challenge to implementing research guided by ISEM is
the intense data requirements. Data collected at multiple levels
(e.g., individual, community, environment), data on social and
physical exposures, and longitudinal and spatially resolved
data are required. A particularly informative design would
be prospective cohort studies that collect data on as many
elements delineated by ISEM as possible, for prolonged pe-
riods of time. Such studies would include a wide range of
social and environmental factors that tend to typically
co-occur, evaluate interacting bio-behavioral pathways across
the life span, and consider effects of both adverse and protec-
tive factors on health and well-being.
As such data-intense research may not always be feasible, a
strategic alternative could be to focus research on specific pro-
cesses that connect joint exposures to socio-environmental fac-
tors to health and well-being. Key elements of the ISEM can be
used to define these sub-areas of research focus (see Table 1).
Specifically, we suggest that future research focus on character-
izing the interdependence and interplay of the physical and social
environmental factors. Some of these interactions are complex
and take place through bi-directional pathways that extend across
the life span, instead of primarily resulting from concurrent ex-
posures over short periods of time. Thus, such research will also
need to incorporate a life course perspective. An example would
be the interaction between childhood adversity, inflammatory
pathways, and vulnerability to air pollution exposure discussed
in the previous section. A fruitful research approach to tackling
these questions could consist of strategically designed experi-
mental research to test specific causal hypotheses regarding
whether and how interactions between social and environmental
factors directly alter biological functioning and behavior. Both
human studies animal models may be informative. For example,
in humans, natural experiments (e.g., near highway or commuter
exposure) can be used to determine if stress across the life span
exacerbates the biological responses (e.g., inflammation) to air
pollution exposure. While in animals, control-exposure experi-
mental designs can be used to study the interactions of stress and
air pollution exposure in more detail and discern relevant mech-
anistic pathways. For example, one study exposed 24 rats to
either air pollution only, stress only, or air pollution and stress,
and found that stress mediated the effect of air pollution on re-
spiratory patterns [112]. While few studies in this area have been
conducted, greater insight may be gained with more work like
this; such studies can more directly test causal hypotheses related
to the interplay between stress and environmental toxicants on
specific health outcomes.
Research that focuses on potential protective or mitigating
effects of combined socio-environmental exposures is also
greatly overdue, as is exploring the role of culture. In this
regard, the ISEM is ideally structured to support the study of
pathways of resilience, specifically to delineate the processes
or factors that can change the path of a joint exposure to
socio-environmental factors ways that determines if an out-
come is positive or not. To this end, we propose that future
studies focus not only on identifying protective factors but
also on exploring the pathways that lead to positive outcomes.
 Curr Envir Health Rpt

Table 1 Key characteristics of

ISEM and how it can support
future research
Strengths of ISEM
Explicitly considers the interdependence and joint
contribution of physical and social environmental
factors to health outcomes
Adopts an ecological perspective in which the
individual is nested within communities and
embedded in a larger culture
Incorporates moderating effects by resources and
susceptibilities that can be intrinsic to the individual
as well as shaped by the environment (contextual)
Outlines a progression connecting exposure to
outcome to support study of pathways and
mechanisms of action
Recognizes that environmental factors can lead to
either adverse or protective outcomes depending on
the pathway
The applicability of the model extends to processes
that are relevant across the life span or
transgenerationally
Priorities for future research
Characterize the nature of the relationship between
physical and social environmental factors with
health outcomes (e.g., synergies, mediation,
moderation)
Explore the role of culture in the exposure-outcome
continuum at the individual and community level
Determine how social and physical environmental
factors can interact by shaping the resources and
susceptibilities that could augment or diminish the
response to each other
Construct and test plausible bio-behavioral pathways
through which exposure to specific social and
environmental factors impact health and well-being
Distill modifiable bio-behavioral factors that can cause
a joint socio-environmental exposure to lead to a
positive outcome (e.g., pathways of resilience)
Understand how physical and social environmental
factors can interact to engrain susceptibilities that
drive health disparity across generations

Understanding the mechanisms underlying how the total
environment embeds lifelong susceptibilities that drive health
disparities across generations is imperative. Given the increas-
ing technical capability for “omics” research and for obtaining
such data via sensors and monitors, as well as the rapidly
burgeoning literature suggesting the insights to be gained from
these processes, one important first step is to begin to assess the
role of the epigenome and microbiome as central mechanisms
underlying synergistic effects of social and environmental fac-
tors and on health and well-being. This type of work is valuable,
as it will increase our understanding of how joint
socio-environmental factors can produce susceptible or resilient
phenotypes that shape health and well-being throughout the life
span. Finally, studies are urgently needed that focus on how
combined exposures to socio-environmental factors can imprint
lifelong and even trans-generational susceptibilities that drive
and potentially perpetuate health disparities across social strata.
Conclusions
sophisticated technical and analytic capacity, this model can help
to establish a solid foundation for rapid advancements that can
inform policy, public health, and practice.
Acknowledgments This work was funded by the JPB Environmental
Health Fellowship Program granted by The JPB Foundation and man-
aged by the Harvard T.H. Chan School of Public Health. The authors
thank the JPB fellows for the helpful discussion in developing the ideas
put forward here. The authors also thank Nicolle Tulve (EPA), Rachel
Morello-Frosch (UC-Berkeley), Madeleine Scammell (Boston
University), and Jose Ricardo Suarez (SDSU) for their helpful comments
on the manuscript.
Compliance with Ethical Standards
Conflict of Interest Hector A. Olvera Alvarez, Allison A. Appleton,
Christina H. Fuller, Annie Belcourt, and Laura D. Kubzansky declare that
they have no conflict of interest.
Human and Animal Rights and Informed Consent This article does not
contain any studies with human or animal subjects performed by any of
the authors.

The ISEM draws from multiple research disciplines to build a

broad perspective on how social and physical environmental
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