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Gut health in poultry

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DOI: 10.1079/PAVSNNR201712031

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 CAB Reviews 2017 12, No. 031

Gut health in poultry

Michael H. Kogut1*, Xiaonan Yin2, Jianmin Yuan2 and Leon Bloom3

Address: 1 Southern Plains Agricultural Research Center, USDA-ARS, College Station, TX 77845, USA. 2 State Key Laboratory of
Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China. 3 Faculty of Biological
Sciences, University of Leeds, Leeds LS2 9JT, UK.

*Correspondence: Michael H. Kogut. Email: mike.kogut@ars.usda.gov

Received: 14 June 2017

Accepted: 21 August 2017

doi: 10.1079/PAVSNNR201712031

The electronic version of this article is the definitive one. It is located here: http://www.cabi.org/cabreviews

© CAB International 2017 (Online ISSN 1749-8848)

Abstract

Although the gastrointestinal tract is frequently described simply as ‘the gut’, it is actually made up of:
(1) an epithelium; (2) a diverse and robust immune arm, which contains most of the immune cells in
the body; and (3) the commensal bacteria, which contain more cells than are present in the entire
host organism. Understanding of the crosstalk between ALL of these interrelated components of the
gut is what cumulatively makes the gut the basis for the well-being of animals and the motor that
drives their performance. Optimal gut health is of vital importance to the performance of production
animals and is synonymous in animal production industries with animal health. There does appear to
be a direct relationship between animal performance and a ‘healthy’ gut, there is no clear definition
that includes all the physiological functions of the intestinal tract, including nutrient digestion and
absorption, host metabolism and energy generation, a stable microbiome, mucus layer development,
barrier function and mucosal immune responses. The most basic function of the gut is regulating
physiological homeostasis that provides the host the ability to withstand infectious and non-infectious
stressors. This review updates our understanding of the interactions between the diverse
physiological features of the gut and emphasizes the extent of areas encompassed by gut health
and the ability to regulate animal production.

Q1 Keywords: Gut health, Poultry, Microbiome, Mucosal immunity, Tight junctions

Modern poultry operations have undergone dramatic
changes in production practices over the last 50 years.
Genetic selection for high growth rates and reproductive
traits as well as improved management techniques and
dietary requirements has led to increased performance
standards in all livestock operations. However, it is
reasonable to question whether, in the near future,
animal performance will reach a ceiling due to genetic
and/or physiological limits. It is with these limits in mind
that over the last 10 years, the expression ‘gut health’ has
entered the collective consciousness of animal industries
and research [1, 2]. The expression ‘gut health’ has become
the standard in the scientific literature and animal pro-
duction industries to describe animal health. Within the
scientific literature, there has been an exponential increase
in the use of ‘gut health’, ‘intestinal health’, ‘enteric health’
or similar terms, and great interest in the development of
this concept. However, whilst the words ‘gut’, ‘intestinal’
and/or ‘enteric’ clearly relate to the gastrointestinal tract,
defining ‘health’ can be more problematic, making the actual
definition of ‘gut health’ difficult. However, there is no clear
definition for the term gut health. Furthermore, from a
scientific point of view, no one can state what gut health is,
how it can be defined and, most importantly, how it can be
measured. Interest in ‘gut health’ has, at least partially,
increased due to the European Union ban of antibiotic
growth promoters (AGPs) [3] and similar policies in other
countries/regions [4]. Whilst the precise mode of action of
AGPs has still not been fully established, their withdrawal
from animal feeds is clearly associated with increased
incidence of intestinal disorders. For example, prior to
2006, necrotic enteritis was not recognized as a major
poultry disease [5], but has subsequently grown in
prominence to become, arguably, the most important and
costly disease of poultry [6]. Against this background, the
livestock industry strives to increase productivity and

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2 CAB Reviews
efficiency. These facts lead us to consider the structure of
the intestine, its optimal functioning and how this can be
influenced to enhance animal health and productivity.
What is Gut Health
Gut health lacks a clear definition and because of the scope
of scientific disciplines involved in maintaining and achieving
gut health, no one clear definition is all-encompassing. To
paraphrase US Supreme Court Justice Stewart Potter when
asked to describe his threshold test for obscenity in
Jacobellis v. Ohio (1964), the poultry industry describes
what gut health is by stating ‘I know it when I see it’. Since
we all know that the gut essentially refers to the
gastrointestinal tract, the definition of gut health hinges
on defining ‘health’. The simple definition would be
‘absence of overt disease’. However, overt disease is not
required to affect animal production.
To further emphasize the complexity of the intestinal
milieu, one needs to understand that the gut is the natural
habitat for a large and dynamic community of microbes that
are participants that regulate not only intestinal, but also
systemic functions of the host [7–12]. Further, the gut
comprises the major barrier that separates the largest
interface between the external environment and the
internal milieu while still allowing molecules to be absorbed
or secreted [9, 10, 13]. Thus, the gut and its integral
components are functionally dependent for the proper
physiological development of the host. Perhaps a more
meaningful definition would be defined as the ability of the
gut to perform normal physiological functions and to
maintain homeostasis, thereby supporting its ability to
withstand infections and non-infectious stressors. This
definition incorporates the underlying components of gut
health: effective digestion and absorption of food, a stable
gut microbial population, structure and function of the gut
barrier, and effective function of the immune system, all of
which play a critical role in gut physiology, the productivity
of the animal and its well-being. Comprehension of gut
health requires the elucidation of the interactions between
all of these components as well as the scope of areas
encompassed by gut health. New technologies and meth-
odologies have positioned research in ‘gut health’ to
advance rapidly in both basic and applied directions.
Research will focus issues of public concerns about food
safety and the use of new ‘big data’ stemming from systems
biology (‘omics).
Over 2000 years ago, Hippocrates c. 400 BC believed
that ‘all disease begins in the gut’ and ‘death sits in the bowel’.
Poultry live in environments full of microbes where every
day they are exposed to untold numbers of potentially
pathogenic agents through the air, water and food they
consume, and contact with house and pen mates. Thus, it is
doubtful that a broiler is ever ‘free’ of disease. We prefer to
define a healthy bird as one that is able to perform its
physiological functions to meet its performance standards.
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Performing as expected suggests that the bird is able to
maintain an intestinal homeostasis and withstands environ-
mental stressors.
Components of Gut Health
When discussing gut health, we are really talking about a
number of physiological, microbiological and physical
functions that work together to maintain intestinal homeo-
stasis [14–16]. The most fundamental function of the gut
is effective digestion and absorption of dietary nutrients
[151, 17]. As the organ with the largest surface area with Q2
constant interaction with the environment, the gut must
provide an effective barrier function (epithelial lining),
which reduces exposure to environmental toxins and
potential pathogenic microbes yet allows for nutrient
absorption and waste secretion [18]. A further crucial
functional component of the gut is an effective immune
system [19, 20]. The gut also provides a platform for the
growth of a diverse microbiota that provides not only a
second barrier against colonization by pathogens, but which
also regulates immune development and maturation, and
provides metabolites for host nutrition [21–23]. Lastly, the
gut contains a large number of neurons, gut hormones
and secondary messengers so that it is considered to be
the largest neuroendocrine organ in the body and
thus regulates a plethora of host physiological functions
[24–26].
Therefore, maintenance of optimal intestinal function
(gut health) is dependent on three interdependent
components: (1) immune system; (2) microbiota; and
(3) nutrition (Figure 1), which influence host physiology
and metabolism.
Immune system
The intestinal immune system includes a robust mucosal
layer, tightly interconnected intestinal epithelial cells,
secreted soluble immunoglobulin A and antimicrobial
peptides (AMPs). The mucosal layer consists of an outer
loose layer in which microorganisms can colonize and an
inner compact layer, which repels most bacteria. As a
component of the intestinal mucosal innate immune
system, the mucus layer prevents gut microorganisms
from penetrating into the intestinal epithelium and serves
as the first line of defence against infection. Below the
Immune system
Microbiota Nutri
on
Figure 1. The interconnected intestinal menage a trois.

mucus layer, a single layer of epithelial cells separates the
densely colonized, and environmentally exposed, intestinal
lumen from the largely sterile subepithelial tissue. A subset
of intestinal epithelial cells secrete AMPs (defensins,
cathelicidins, C-type lectins), which are a key defence
against luminal microbes. Linking the epithelial cells are
tight junctions, which help form a continuous luminal
surface and help seal the intercellular space, near the
apical surface, from the external environment. These
tight junctions are formed by protein (claudins, occludins
and zona occludens protein 1) complexes. In addition,
secretory IgA, produced by intestinal B cells, provide an
additional protective layer from the luminal bacteria [27].
Both antimicrobial host defence and homeostasis rely on
signalling pathways induced by innate immune receptors
[28, 29]. Enterocytes express pattern recognition recep-
tors (PRRs), including toll-like receptors (TLRs) and
Nod-like receptors (NLRs) that sense conserved pathogen
molecular signatures [30]. The TLRs and NLRs remain
relatively non-responsive to the myriad of commensal
microbiota during homeostasis, but during infection, injury,
or another environmental insult, the PRRs initiate a cascade
of events that contribute to the induction of an inflamma-
tory response [20, 30]. However, occasional breeches of
the gut epithelium do occur. Innate immune sensing,
mediated through the PRRs on the epithelial cells, lamina
propria dendritic cells and macrophages, initiate various
immune pathways that mediate microbial killing and activate
the acquired immune effector cells while keeping the
resident microbiota in check without generating an overt
inflammatory response.
Gut immune responses are tightly controlled to remain
tolerant of the commensal microbiota, while concurrently
maintaining the capacity to respond appropriately to
harmful insults. Several cellular and molecular mechanisms
have evolved to contribute to effective balance
(homeostasis), whilst attenuating damaging overreactions
or altering the metabolic functions of the microbiota
(dysbiosis). The multiple functions of the gut immune
system (i.e. avoid detrimental responses to food antigens
and commensal microbes, prevent pathogen invasion and
translocation to extra intestinal sites and exploit beneficial
effects of commensal microbes) relies on the mucosa using
a number of strategic immune cells (macrophages, dendritic
cells, various subsets of T cells [Th1, Th2, Th17, Treg],
intraepithelial lymphocytes, γδT cells) and molecules
(cytokines and chemokines) to maintain immune homeo-
stasis and protect against prolonged inflammation [20, 31].
Dendritic cells present antigens to naïve CD4+ T cells
present in gut lymphoid tissues, such as Peyer’s patches and
caecal tonsils, where differentiation of the effector CD4+ T
cell subsets occurs [20, 32]. In summary, maintaining gut
immune homeostasis, while mounting protective immunity
to pathogens is primarily achieved through: (1) limiting
direct bacterial contact with the intestinal epithelium and
(2) rapid detection and removal of pathogens that penetrate
the epithelium.
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Michael H. Kogut et al. 3
Microbiota
All animals play host to entire communities of commensal
and symbiotic microbes. In the intestine, there are
estimates of up to 1014 bacterial cells, which is around
100 times greater than, for example, host (human or pig)
cells (1012). Thus, the gut microbiome acts as an additional
complex organ within the host, containing more than one
million genes (for comparison, this is about 40–50 times
the number in the entire chicken genome [7, 33]. These
microbes receive their nutrients from the host (or host’s
diet) and, in turn, contribute essential nutrients (see below)
to the host, promote intestinal development, enhance gut
integrity, provide competitive exclusion of pathogens,
modulate the regulation and function of the host immune
system, and sustain immune homeostasis by controlling
physiological inflammation [8, 34–38].
Whilst much of the available data regarding the intestinal
microbiota/microbiome and enteric health relate to
changes associated with a diseased state, there are
clear examples of the importance of the microbiome in
maintaining gut health and normal intestinal function. In
germ-free animals (e.g. mice), both the mucosal and
systemic immune systems are poorly developed and these
animals do not generate normal oral tolerance to dietary
proteins, but these features can be overcome/restored if
these animals are subsequently colonized by a conventional
or defined microbiota. This demonstrates a clear link
between intestinal colonization by microbes and the
development of a normally functioning immune system
[39]. In addition, Nurmi and Rantala [40] demonstrated that
giving chicks the gut contents of healthy adult chickens
profoundly increased their resistance to Salmonella
infection. This contributed to the ‘competitive exclusion’
phenomenon and highlighted the critical role of a ‘normal’
gut microbiota in preventing undesirable microbial coloni-
zation. Moreover, in humans, disturbance of the gut
microbiome through, for example, oral antibiotic therapy
is frequently associated with diarrhoea (antibiotic associ-
ated diarrhoea) typically caused by Clostridium difficile [41].
Unlike the host genome, which is rarely manipulated by
xenobiotic intervention, the microbiome is readily change-
able by diet, antibiotics, infections by pathogens and other
environmental insults [42–44]. The plasticity of the micro-
biome has been implicated in numerous disease conditions
and unfavourable alteration of the commensal structure of
the microbiota is referred to as dysbiosis. Dysbiosis is
manifested by a reduction in the number of tolerogenic
bacteria and an over-growth of potentially pathogenic
bacteria (pathobionts) that can penetrate the intestinal
epithelium and induce disease in certain environmental
settings [38, 45–47]. However, despite being manipulable,
studies in pigs have also shown that the microbiota is
somewhat resilient to change. Whilst weaning of piglets
significantly influenced the gut microbiota, the microbiota
of piglets 4 weeks after weaning still showed greater
similarity with former littermates than to their new pen
4 CAB Reviews
mates after they were mixed at weaning [48]. These results
demonstrate that the microbiota acquired early in life
may be a strong determinant of its later composition.
Additionally, it has been demonstrated that microbiota
and immune system development are influenced by
farm-to-farm differences [48]. Given that, globally, farms
will experience a multitude of gut health scenarios
(i.e. ‘better’ or ‘worse’), this indicates that there are
multiple microbiotas/microbiomes that are associated
with favourable intestinal health. Thus, whilst these may
have common features, it is unlikely that there is a single
microbiota/microbiome that we are striving to achieve but
rather a range of possibilities, which may be dependent on
local conditions.
Nutrition
Host nutrition and endogenous secretions strongly influ-
ence the gut microbiota and (thus) immune system, while
nutritional deficiencies have long been known to impair
immune function. There have been a number of reviews
that have discussed the influence of nutrition on host
immune responses [49–52] and the intestinal microbiota
[53–55]. Nutrition affects a large number of biological
processes vital to the immune response, including gene
expression, protein synthesis, metabolism, signal transduc-
tion and cellular proliferation. Cellular metabolism is
a fundamental activity that incorporates numerous path-
ways used for energy generation and the production of the
precursors required for macromolecule production. Thus,
immune cell survival and function is inherently associated
with nutrition and cellular metabolism of nutrients.
Consequently, the dramatic increases in the understanding
of the organization of the immune system and the factors
that regulate immune function have supported the close
concordance between host nutritional status and immunity.
The dynamic interactions between the gut microbiota and
the immune system mean that microbiota modifications
probably contribute significantly to the reported effects of
nutrition on host immunity. As mentioned, the gut
microbiota derives nutrients from the host’s diet or
endogenous secretions, whilst enhancing the nutritional
value of the diet through the synthesis of essential nutrients
(e.g. vitamins) and the production of complimentary
enzymes (e.g. non-starch polysaccharidases). During the
depolymerization of dietary polysaccharides, gut bacteria
produce short chain fatty acids (SCFAs). Common SCFAs
produced are acetate followed by propionate and butyrate.
Butyrate or butyric acid is the primary energy source of
colonic epithelia and has been shown to be essential to
homeostasis of colonocytes and the development of gut
villus morphology [56]. Butyric acid has been shown to
improve growth performance and carcass quality charac-
teristics in chickens [57, 58]. It has also been reported that
SCFAs can regulate intestinal blood flow, stimulate enter-
ocyte growth and proliferation, regulate mucin production,
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and affect intestinal immune responses [59]. In addition, the
gut microbiota also contributes to nitrogen metabolism.
The microbial metabolism of dietary protein that escaped
host metabolism earlier in the gut provides further
amino acids for egg production, maintenance and growth.
Therefore, whether through direct effects on immune
function, or influences on microbiota composition and
activity, nutrition is an integral component of gut health.
Influencing Gut Health
In the preceding sections, we have outlined the importance
of the key contributors to gut health. Ultimately, the
livestock industry is seeking to promote a beneficial gut
microbiota/microbiome, with effective competitive exclu-
sion capability and/or the ability to help shape desirable
immune responses, and appropriately robust barrier and
immune function. Whilst there are still various unknowns
in this area, there are opportunities to drive gut health in
the right direction. Opportunities to influence gut health
typically focus on modulation of the intestinal microbiome
and/or (mucosal) immune function. Probiotics (micro-
organisms) may be used to colonies the intestine with
microbes with desirable attributes that can promote
competitive exclusion and/or promote beneficial gut
barrier and immune function. Prebiotics (substrates for
microbes) can help shape the gut microbiome and, in turn,
immune capability. Synbiotics is a term used for the
combination of probiotic(s) and prebiotic(s), which
attempt to provide favourable microorganism(s) along
with a nutrient source. There is also interest in exogenous
enzymes (alter substrate availability and digesta viscosity),
plant-derived compounds (antimicrobial and other
potential features), organic acids including butyric acid
(antimicrobial, enhance gut structure and alter pathogen
gene expression) and mycotoxin mitigation (limit intestinal
damage and suppression of immune responses) for
application in the gut health arena. Other, potentially
more novel, attempts to influence gut health through
microbiota and/or immunity modulation include exogenous
provision of AMPs, antibodies (e.g. egg yolk), PRR ligands,
bacteriophages and vaccines. Antibodies and AMPs can help
supplement those innately present in the gut environment
and thus impede (undesirable) bacterial contact with the
epithelium. Bacteriophages are specific viruses that infect
and replicate in bacteria, and can influence host immunity.
Therefore, bacteriophages with appropriate antibacterial
and immunomodulatory activity may represent an effective
option to promote gut health. PRR ligands have the
potential to be used to upregulate innate immune pathways,
through binding to their respective receptor, and thus
promote innate defences. Vaccines can obviously be used
to modulate immunity and generate responses specific to
the antigen challenge. Better understanding of gut health
could lead to specific mucosal vaccines that help shape the
most appropriate immune response.

Conclusions and Future Perspectives
The gut microbiota, immune system and nutrition are
all integral components of intestinal health. However,
precisely defining gut health is currently difficult. It is,
however, clear that an appropriate gut microbiome,
immune system and nutrition are all required for
optimum intestinal health and thus animal productivity. It
is proposed that gut health can be defined as ‘the ability
of the gut to perform normal physiological functions and
to maintain homeostasis, thereby supporting its ability
to withstand infections and non-infectious stressors’.
Although interpretation of data from newer methodologies
can be hampered by the comprehensiveness of currently
available databases, next generation, high-throughput
technologies are set to advance our understanding of gut
health considerably in the coming years, and there is still
much to learn. The gut microbiota remains incompletely
characterized and is often based on the rather crude
comparison of a single gene sequence (16S ribosomal
subunit) to differentiate organisms. In addition, it is likely
that microbiota phenotyping, rather than genotyping, is
more relevant to gut health and thus techniques, which
explore the activities of the microbiota rather than just who
is there, will help expand our understanding. Moreover,
in the future, when considering the entire gut ecosystem,
it may be helpful to better understand the contributions
of, and interactions with, other members of the microbiota
(e.g. yeasts, viruses, parasites), as bacteria are the
typical focus.
We are still some way from fully understanding desirable
immune responses and maintenance of homeostasis in the
intestine. This creates difficult in attempting to appropri-
ately steer immune responses. The negative consequences
of inflammation, the potentially negative relationship
between pro-inflammatory cytokines and poorer animal
performance [60], and suggestions that anti-inflammatory
properties of AGPs are primarily responsible for their
effects [61] have led to the pursuit of exogenous
anti-inflammatory agents to promote animal performance.
However, inflammation is a critical immune response
and studies have shown that selecting animals for
pro-inflammatory mediators increases their resistance to
pathogen challenge [62]. In a commercial setting, it is likely
that animals are exposed to an array of potential (entero)
pathogens that require a rapid and efficient inflammatory
response. Studies in which animals are raised in relatively
‘clean’ environments, where the range and load of potential
pathogens are lower, may misinform our interpretation
of the type of immune responses desired in practice.
Future immunological studies should help to delineate
desirable immune pathways for both robust gut health
and to promote animal performance in a range of rearing
environments. Technologies, such as species-specific
peptide arrays, offer the opportunity to move away
from the limitations of gene expression assays, better
explore downstream global cellular signalling events and
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Michael H. Kogut et al. 5
simultaneously consider immunology and metabolism, and
their interaction (immunometabolism). Q3
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Author Queries:
Q1: Please provide ‘Review Methodology’ for this paper.
Q2: Please advise should it be appropriate to delete the reference citation [151] in the sentence ‘The most fundamental function of the
gut is effective digestion and absorption of dietary nutrients’.
Q3: Please provide details of acknowledgement.

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