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PERSPECTIVE
published: 14 June 2022
doi: 10.3389/fvets.2022.929805
Frontiers in Veterinary Science | www.frontiersin.org 1June 2022 | Volume 9 | Article 929805
Edited by:
Keelin Katherine Mary O’Driscoll,
Teagasc, Ireland
Reviewed by:
Daniel M. Weary,
University of British Columbia, Canada
*Correspondence:
Marian Stamp Dawkins
marian.dawkins@zoo.ox.ac.uk
†These authors have contributed
equally to this work
Specialty section:
This article was submitted to
Animal Behavior and Welfare,
a section of the journal
Frontiers in Veterinary Science
Received: 27 April 2022
Accepted: 16 May 2022
Published: 14 June 2022
Citation:
Düpjan S and Dawkins MS (2022)
Animal Welfare and Resistance to
Disease: Interaction of Affective States
and the Immune System.
Front. Vet. Sci. 9:929805.
doi: 10.3389/fvets.2022.929805
Animal Welfare and Resistance to
Disease: Interaction of Affective
States and the Immune System
Sandra Düpjan 1† and Marian Stamp Dawkins 2
*†
1Institute of Behavioural Physiology, Research Institute for Farm Animal Biology (FBN), Dummerstorf, Germany, 2Department
of Zoology, University of Oxford, Oxford, United Kingdom
Good management and improved standards of animal welfare are discussed as
important ways of reducing the risk of infection in farm animals without medication.
Increasing evidence from both humans and animals suggests that environments
that promote wellbeing over stress and positive over negative emotions can reduce
susceptibility to disease and/or lead to milder symptoms. We point out, however, that
the relationship between welfare, immunity, and disease is highly complex and we
caution against claiming more than the current evidence shows. The accumulating but
sometimes equivocal evidence of close links between the brain, the gut microbiome,
immunity, and welfare are discussed in the context of the known links between mental
and physical health in humans. This evidence not only provides empirical support for
the importance of good welfare as preventative medicine in animals but also indicates a
variety of mechanisms by which good welfare can directly influence disease resistance.
Finally, we outline what still needs to be done to explore the potential preventative effects
of good welfare.
Keywords: affective state, immunity, welfare, gut microbiome, wellbeing, antibiotic resistance
INTRODUCTION
The spread of anti-microbial resistance (1,2) and the devastating effects of diseases, such as
influenza, covid, malaria, and TB, are grim reminders that even with the full resources of modern
medicine at our disposal, we are only just keeping ahead in the arms race against current and
emerging diseases. Furthermore, the current emphasis on the need to reduce the use of antibiotics
e.g., (3,4) removes an important means of safeguarding both human and animal health (5). There is
thus an urgent need to find new ways of fighting disease, preferably ones that do not use medication.
In this study, we focus on the growing evidence that an important way of reducing the risk of
infection may be through good management and improved standards of animal welfare. We draw
on evidence from both humans and animals that environments that promote wellbeing over stress
and positive over negative emotions can reduce susceptibility to disease or at least lead to milder
symptoms and quicker recovery. However, the relationship between welfare, immunity, and disease
is highly complex (6,7), and there is no simple connection between “happiness” and resistance to
infection. Therefore, we caution against claiming more than the evidence shows and outline what
still needs to be done to explore the potential preventative effects of good welfare.
Düpjan and Dawkins Affective State and Immunity
POSITIVE AND NEGATIVE WELLBEING
Historically, the majority of studies on wellbeing, affective
states, and health have focused on negative wellbeing, such as
the negative effects of acute or chronic distress on morbidity
and mortality (8–10). However, human health has long been
acknowledged to be more than just the absence of disease (11).
Similarly, animal welfare is not just the absence of stress and
negative states (12,13). Approaches such as the Five Freedoms
(14) and Welfare Quality (15) emphasize the importance of going
beyond physical health and including mental health as well.
Physical health is ensured by keeping animals in clean, safe, and
comfortable conditions and making sure that they have adequate
access to water and nutritious food. Mental health is achieved by
keeping them in conditions in which they have predominantly
positive emotions associated with having what they like and want
(16,17).
WELLBEING AND HEALTH—EVIDENCE IN
HUMANS
In human medicine, the relatively new interdisciplinary field of
Affective Immunology studies the links between emotion and the
immune system. This covers both the way the immune system
affects the emotional state and also the way that emotions alter
the status of the immune status (7,18). Studies investigating
these links in humans use different approaches and constructs,
making it difficult to interpret results and draw conclusions for
non-human species. The term “wellbeing” includes eudaimonic
wellbeing (whether someone sees their potential fulfilled or
has a sense of purpose in life), hedonic wellbeing (having
pleasurable experiences), and optimism (the expectation of
positive results) (12,13,19). Health outcomes, on the other
hand, are conceptualized as morbidity/recovery from disease,
mortality/longevity, activation of certain parts of the immune
system or associated systems (especially the cardiovascular
system), or self-reported health. This diversity of concepts
and measures, together with variation in sample sizes and
potentially confounding variables (20), has led to controversial
results and confusion about the direction of causation. However,
systematic reviews and meta-analyses have helped to clarify
the picture.
The meta-analyses by Chida and Steptoe (9) provides
evidence for the protective effects of psychological wellbeing
on mortality, although they are more controversial for already
diseased populations (8). A more recent meta-analysis by
DuPont et al. (13) found that hedonic wellbeing is linked to
better hemodynamic recovery after stress, which might reduce
the risk of developing stress-related cardiovascular diseases.
Furthermore, good immune function is closely related to peoples’
subjective reports of being happy and satisfied with their lives
(21,22). Conversely, impaired immune function has been found
in people distressed by circumstances such as homelessness (23),
and mental illnesses such as schizophrenia and depression are
associated with an increase in the cellular immune response
(24,25) and neuronal cell surface antibodies (26,27). Chronic
stress can result in glucocorticoid receptor resistance that in turn
leads to an inflammatory immune response that is pathologically
out of control (28). On the other hand, conscientiousness
has been linked to better health and more supportive social
relationships (29), Tai Chi exercises can improve mental and
physical health in persons with cardiovascular disease (30), and
mindfulness-based training can improve emotional wellbeing
as well as physical function and health (31). However, overall
optimism does not seem to be linked to health as clearly
as hedonic wellbeing (13) or not at all when controlling for
other influencing factors in the statistical models (29). Even
though optimistic patients might be more likely to persevere
with therapy (29), optimistic judgements about health status
might prevent someone from seeking timely medical advice
(8). Indeed, Luo et al. (32) found that, during the COVID-
19 pandemic, people worrying less about the disease showed
less safety-seeking behavior, while perceived risk correlated
negatively with wellbeing.
WELLBEING AND HEALTH—EVIDENCE IN
ANIMALS
What is true for humans is now increasingly seen as applying
to animals too (33). Human depression is associated both with
chronic inflammation and compensatory responses to combat
inflammation (34,35), and there are clear parallels to stress
responses in animals (36). For example, mice that are repeatedly
subjected to stress such as being defeated in social encounters
show an inflammation response throughout the body including
enhanced neutrophil and cytokine activity (37). Social stress
in pigs caused by fighting suppressed the immune response to
a viral vaccine (38) while groups with low aggression social
support can buffer acute stress responses in both humans (39)
and other species (40,41), with positive effects on the immune
system (42,43). It follows that providing stable social groups is
a promising way of not only reducing injuries but also avoiding
inflammation resulting from the stress of aggression. Giving
animals the opportunity to feed undisturbed by conspecifics can
have beneficial effects. In a cognitive enrichment experiment pigs
had to learn their names and were then called to a feeding station,
where they could then eat by themselves, and this had positive
effects on health (44) and affective state (45–47).
The physical environment can also affect immune responses
(48,49). For example, enriching the environment of turkeys with
“turkey trees” led to an increase in circulating white blood cells
(50), and providing pigs with enrichments such as straw and
branches resulted in a series of immunological changes including
a higher percentage of T cells (51). Providing pigs with straw
bedding can reduce the risk of gastric lesions (52), and young pigs
with social and environmental enrichment were less susceptible
to co-infection of PRRSV and Actinobacillus pleuropneumoniae
and showed healthier lungs (53). Environmental enrichment
early in life can also have positive effects on the development of
the immune system and the establishment of gut microbiota in
pigs (51).
Frontiers in Veterinary Science | www.frontiersin.org 2June 2022 | Volume 9 | Article 929805
Düpjan and Dawkins Affective State and Immunity
WELLBEING AND HEALTH—WHAT WE
STILL NEED TO KNOW
Although animal welfare as a way of controlling a disease is
an attractive proposal with worldwide implications for both
animal and human health, it is based on many ideas that are
still largely untested (16,33). The interactions between the
brain, gut microbiome, and immune system are highly complex
(36,54,55), and there is consequently no simple relationship
between measures of immune activity and welfare. Evidence that
improved animal welfare can lead to a reduction in infection may
be true in some cases, but it is important not to claim more than
the evidence shows.
One reason for caution is the complexity of the immune
system itself. The vertebrate immune system consists of an
extraordinary range of defense mechanisms, including the
physical barrier of the skin that helps to prevent pathogens
from entering the body as well as a whole range of specialized
cells in the blood and lymphatic systems for detecting and
destroying pathogens if they do get inside the body. In addition,
an ecosystem of bacteria and other organisms living in the gut
also has a profound effect on health in general and immune
function in particular (54–56).
Immune responses occur in two stages which have very
different implications for welfare. The innate or non-specific
cellular immune system provides the first set of responses
to infection or injury including the production of bacteria-
destroying granulocytes, the release of cytokines, and local
inflammation together with a whole range of sickness responses
such as fever. It is an all-purpose emergency reaction, stimulated
by a wide range of dangers and involving many different
parts of the body. It needs such a high level of nutrients to
keep it functioning that fighting disease may result in more
resources being put into immune function and less into growth
(57). Conversely, when animals become stressed, a cascade of
hormonal responses including the release of corticosteroids or
stress hormones shifts the entire metabolism away from immune
responses and toward releasing readily available energy for taking
some kind of action.
The second stage in the immune response is the more targeted
“acquired” immunity stage which consists of the development of
specific antibodies against particular diseases, in which the body
“discovers” the correct antibody against a particular disease and
then clones multiple copies. A relatively small number of specific
antigens then provide long-lasting protection against infection.
Given the complexity of these immune reactions and their
interactions with both the gut microbiome and the emotions,
there are also many different ways in which immunity can affect
and be affected by emotional state (10,58). First, changes in the
immune system, such as inflammation, may directly affect, and
be affected by, the emotional state (7,13,59). Second, immunity
and emotional state may be linked by more indirect routes, for
example, via effects on the cardiovascular system (e.g., (8,13,60)
and the gut microbiome (61). The gut microbiome is a complex
community of viruses, bacteria, archaea, and eukaryotes, the
composition of which is strongly influenced by factors such as
diet and the neurological and endocrinological responses of the
body to stress (62). In turn, the microbiome affects how the
body responds to stress and to disease challenges (61,63,64).
Even more indirectly, the immune response can be influenced
by behavioral changes such as dietary choice, rest or activity,
and avoidance of other individuals, all of which can result in
a reduced risk of disease and/or faster recovery from disease.
Looking through the literature on the links between wellbeing
and health in humans, despite known physiological pathways
(8,10), the most meaningful pathway between immunity and
health seems to be via behavior (20). The happiest and most
conscientious individuals tend to make less risky decisions and
instead engage in behaviors that improve their health, such as a
healthier diet and regular exercise (9,29).
There are thus many different ways in which improving
standards of animal welfare might influence immunity because
there are so many different ways in which the immune system
is influenced by, and exerts influence on, so many other systems
of the body. There is much that we still do not understand and
much we still have to learn. It is also important to remember that,
even if a particular practice, such as an improvement in welfare
management, affects immune responses, this is only the first step
toward the much stronger claim that improved welfare protects
against disease.
Many studies on the effects of welfare on disease, including
most of those cited in this article, have been conducted by
comparing the body’s immune response in different conditions
and then drawing conclusions about the potential effect this
might have on the ability to resist actual infection. From such
evidence, it is often concluded that keeping animals in the
higher welfare conditions would improve their ability to resist
disease. Now while this is a plausible inference from the evidence
presented, it is by no means certain that this would be the case
out there in the real world. A disease may be so severe that the
immune system, although making a valiant attempt to protect,
will be ineffective at resisting infection.
While tests of immune response under controlled conditions
are an essential preliminary, we also need on-farm studies to
demonstrate that farm animals can actually realize the full
potential of their immune function under real-world conditions.
The ultimate test of the protective effect of good animal
welfare must therefore be evidence that, under commercial farm
conditions, animals kept in high welfare conditions are less likely
to fall victim to disease or more likely to recover quickly, along
with guidance about the limitations of what improved welfare can
achieve. To exaggerate the effects of good management on disease
resistance could be as counter-productive as ignoring the effects
of good welfare altogether. There is an urgent need for research
in this area and it needs to be based on evidence collected in the
real world.
THE PATH TO BETTER WELFARE
Even knowing more about the relationship between disease
resistance and welfare will not, however, resolve fundamental
issues about how to implement them in practice. Indeed, there
may be conflicts about how best to reduce the risks of different
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Düpjan and Dawkins Affective State and Immunity
diseases. In dairy cattle, access to pasture can reduce the risk of
mastitis, claw health, and other health issues, but this can come
with a higher risk for parasitism and malnutrition (65).
For some people “improving welfare” means moving toward
free-range systems and away from intensive indoor methods
of production altogether, despite these extra risks. There is a
widespread assumption that animals are more likely to be healthy
and to have positive emotions if they can show more “natural
behaviour” (66–68) and the health risk of reduced biosecurity
is judged as less important than the positive welfare benefits of
a more “natural” life (69). In complete contrast, other people
see the route to better welfare being through the increased use
of technology that allows not only improved biosecurity but
the provision of optimal environmental conditions that allow
the immune system to function more effectively. For example,
heat stress is a major form of poor welfare, leading to a variety
of pathologies, including making animals more susceptible to
infection (51,70). Amongst other effects, heat stress damages
the intestinal mucosa of poultry, making it more likely that
endotoxins and even bacteria will enter the bloodstream (71). The
controlled indoor conditions achievable by smart farming can do
a great deal to reduce heat and other stressors (72). On the other
hand, there may be adverse consequences for resistance to other
diseases caused by high stocking densities or other features of
intensive systems (73).
These two opposite views of how to improve welfare—more
extensive outside “natural” living versus more intensive indoor
technology-led living—clearly have very different implications
for disease risk, both for the chances of animals encountering
infective organisms in the first place and also for how their bodies
might later react to being infected. There are no simple answers
and future developments will need to find a balance between the
costs and benefits of different systems. Animal welfare is only one
of many weapons we have in the fight against infection, one that
has perhaps not yet been fully appreciated but one where our
knowledge is still very incomplete.
CONCLUSIONS
The hypothesis that good animal welfare optimizes the
conditions in which the body’s own natural defenses operate
most effectively and can therefore be an effective weapon against
infectious disease is a potential of major significance to both
animal and human health. However, it currently lacks good
supporting evidence, and it is important not to oversell the idea
or exaggerate the ability of good animal welfare to substitute
for medication. To test the hypothesis, it will be necessary to
demonstrate that high welfare conditions (carefully defined)
actually do protect against disease, not just in theory, in the
lab, or in experimental conditions but in real-world commercial
conditions. There may have to be many caveats, such as that
good welfare can offer protection with some diseases but not
others or that some aspects of “good welfare”, such as avoiding
diseases associated with overheating, may be in conflict with
what is meant by “good welfare” in some other respect such as
allowing animals to range outdoors. With two things as complex
as disease prevention and animal welfare, we should not expect
simple solutions.
However, the accumulating evidence of close links
between the brain, the gut microbiome, immunity, and
welfare as well as the known links between mental
and physical health in humans not only provides
empirical support for the importance of good welfare
as preventative medicine but also indicates a variety of
mechanisms by which good welfare can directly influence
disease resistance.
DATA AVAILABILITY STATEMENT
The original contributions presented in the study are included
in the article/supplementary material, further inquiries can be
directed to the corresponding author.
AUTHOR CONTRIBUTIONS
All authors listed have made a substantial, direct, and intellectual
contribution to the work and approved it for publication.
FUNDING
The publication of this article was funded by the Open Access
Fund of the FBN.
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