Accepted Manuscript

Title: The central role of intestinal health on the effect of feed

additives on feed intake in swine and poultry

Author: P.J. van der Aar F. Molist J.D. van der Klis

PII: S0377-8401(16)30443-6
DOI: http://dx.doi.org/doi:10.1016/j.anifeedsci.2016.07.019
Reference: ANIFEE 13598

To appear in: Animal Feed Science and Technology

Received date: 12-8-2015

Revised date: 5-1-2016
Accepted date: 31-7-2016

Please cite this article as: van der Aar, P.J., Molist, F., van der Klis,
J.D., The central role of intestinal health on the effect of feed additives
on feed intake in swine and poultry.Animal Feed Science and Technology
http://dx.doi.org/10.1016/j.anifeedsci.2016.07.019

This is a PDF file of an unedited manuscript that has been accepted for publication.
As a service to our customers we are providing this early version of the manuscript.
The manuscript will undergo copyediting, typesetting, and review of the resulting proof
before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that
apply to the journal pertain.
Running head: Intestinal health, feed additives and feed intake

The central role of intestinal health on the effect of feed additives on feed intake in swine
and poultry

P.J. van der Aar*1, F Molist* and J.D. van der Klis#

*
Schothorst Feed Research, P.O. Box 533, 8200 AM Lelystad, the Netherlands; and
#
Delacon Biotechnik GmbH, 4221 Steyregg, Austria

1
corresponding author: pvdaar@schothorst.nl

The authors contributed equally to this paper

Highlights:

Feed additives and feed intake for pigs and poultry

 Overview on how different factors affect intestinal health

 The mode of actions of various additives on gastro-intestinal health are described.
 Relation of feed additives and feed intake is discussed.

ABSTRACT

Additives are commonly added to animal diets to stimulate production performance, and to
improve welfare and health especially in stressful periods of life. The higher production
performance generally will be a result from a higher feed intake, better digestion and absorption
of nutrients, from improved intestinal health or resilience against systemic challenges or a
combination thereof. Many feed additives have a direct or indirect effect on improving the integrity
of the intestinal epithelium and on the amount of fermentable substrate available for the intestinal
microflora. The mechanism by which these effects influence feed intake are discussed in general
terms. Due to the wide variety of modes of actions by which feed additives can stimulate feed
intake (by improving intestinal integrity, preventing intestinal damage, compensating for additional
nutritional requirements for immune response, reducing the amount of substrate for the microflora
or preventing inflammation) or reduce feed intake (by the addition of feed enzymes to improve
dietary energy value or feed refusals due to organoleptic problems associated with the addition
of medium chain fatty acids and organic acids at high inclusion levels) it is difficult to conclude on
general effects. Moreover, since different additives might partially have similar effects, it can be
expected that these effects are not additive. The direct or indirect effects of specific feed additives
such as pro- and prebiotics, medium chain fatty acids, mycotoxin binders, organic acids, amino
acids, emulsifiers, enzymes, anticoccidials, phytogenic compounds on affecting feed intake in
swine and poultry species are separately discussed.

Abbreviations: AA, amino acids; ANF, anti-nutritional factors; ADFI, average daily feed intake;
ADG, average daily gain; C. perfringens, Clostridium perfringens; deoxynibalenon, DON; E. coli,
Escherichia coli; FCR, feed conversion ratio; FB-1, fumonisin B1; GIT, gastrointestinal tract;
HSCAS, hydrated sodium calcium aluminosilicates; IGF-1, insulin-like growth factor; IPEC,
intestinal porcine epithelial cell; LPS, lipopolysaccharide; Lys, lysine; MCFAs, medium-chain fatty
acids; SCFA, short-chain fatty acids; TEER, trans-epithelial electrical resistance; Thr, Threonine.
Keywords: Intestinal health, Fermentation, Microflora, Stress, Feed additives

1. Introduction

Feed additives have received muchattention from the feed industry over the last few decades,
especially after the ban of in-feed antibiotics as growth promoters in Europe in 2006. It has
stimulated the search for alternatives for these in-feed antibiotics, with a focus on feeds for young
animals like piglets and broilers. Initially this search was focused on alternative antibacterial
effects, but in time nutritionists also appreciated other effects of these in-feed antibiotics like
improving intestinal integrity and their anti-inflammatory responses. The majority of experiments
conducted in swine and poultry, however, were performance experiments in which the additive
was evaluated against a non-supplemented control for registration purposes. In several cases,
feed additives have a reasonable track record for improvement in feed conversion. Information
on their physiological, immunological, and microbiological modes of action is limited.

In the literature various modes of actions of feed additives on the gastro-intestinal tract (GIT)
processes have been described (Turner et al., 2005).

a. Palatability enhancers
b. Improved supply of nutrients
c. Reduced endogenous protein production and losses
d. Reduced microbial growth
e. Reduced inflammation and gut permeability
f. Increased binding of toxins
g. Enhanced intestinal recovery and function
h. Increased colonization and improved microbiome

Positive responses of feed additives on production performance are often associated with
elevated feed intake levels which in turn will result in a better performance of the animals.
However in other situations, the improved nutrient digestibility or reduction of microbial growth
can result also in improvedperformance of the animals without increased feed intake. Various
factors affect gastro-intestinal health, like management and micro-climate, pathogenic pressure
and feed composition. Via a cascade of effects, inflammatory responses are stimulated resulting
in a lower feed intake. Feed additives have in common that they exert an influence on gastro-
intestinal health . In this review we discuss the mechanisms how gastro-intestinal health reduces
feed intake and the effect of different of additives may improve intestinal health and therefore
alleviate the negative effect on feed intake. However, the question remains whether feed additives
have a direct effect on stimulating feed intake and therefore growth performance, and/or an
indirect effect due to improve gut health or gut function.

2. Relation between epithelial damage and feed intake

Feed additives are mainly added in feeds for animals vulnerable to challenges. These challenges
can be of environmental origin (stress, management or infection pressure) or caused by feed
ingredients (ANF’s , mycotoxins or low digestible feedstuffs) via a cascade of reactions influence
the intestinal health and eventually reducing feed intake (Figure 1). In Figure 1 is depicted whether
the effect is in the in the lumen, the intestinal wall or it is a systemic effect. The reduction of
digestive capacity of the intestinal wall the damage of tight junctions play a central role in the
events leading to lower feed intakes.

Animals exposed to stress either by weaning, transport, or mixing with other animals, may show
intestinal ischemia and oxidative stress, resulting in inflammation of the epithelium (Peng et al.,
2012) and reduced intestinal integrity (Nabuurs et al., 1996). Exposure to viruses, bacteria or
parasites compromises intestinal health, and is often a predisposing factor to provoke GIT
problems. Although the mode of action of different pathogens differs, their negative action results
in a reduction of intestinal functions, either through lesions or reduced villus/crypt- ratios, leading
lower ileal digestibility’s and more substrate for the microflora.

Hampson et al. (1985) suggested that rotavirus in piglets was a predisposing factor for weaning
diarrhea, indicating that E. coli could translocate and cause a systemic response only when the
intestinal epithelium was already compromised. Others have shown that an clostridia challenge
following a coccidiosis challenge (Star et al., 2012) or fish meal with high levels of biogenic amines
(Brenes et al., 1987) were essential to induce necrotic enteritis in broiler chickens. Different feed
associated factors that might change the organoleptic characteristics also can exert a negative
effect on intestinal health. Beers et al. (1996) showed that piglets that did not consume feed in
the first days post-weaning had lower villus/crypt ratios than piglets that did eat, suggesting that
periods of malnutrition reduces development of the enterocyte s and intestinal integrity. Anti-
nutritional factors (ANF) may denature proteins in the mucus layer in the intestine resulting in a
disruption of the mucosal barrier. Jansman et al. (1992) showed that lectins from raw Vicia faba
beans increased mucus excretion and decreased the mucus layer in the epithelium of the small
intestine. The increased mucus production leads to an increased supply of nutrients for the
intestinal microflora, and in a malfunctioning of the small intestine. Also phytate as an ANF has a
similar negative effect on increasing the endogenous protein losses. Selle et al. (1999) described
in broilers that the apparent threonine (Thr) digestibility was affected more by dietary phytate level
than any other amino acid due its abundant presence in the mucus proteins. Finally, epithelial
damage may also be induced by the presence of mycotoxins. In poultry epithelial lesions can be
caused by the fusarium toxin T-2. (Ferket and Gernat, 2006). Goossens et al. (2012) showed in
in vitro studies that epithelial cells of pig are vulnerable for the mycotoxins deoxynibalenon (DON)
and especially T-2. Both DON and T-2 decreased trans epithelial electrical resistance (TEER)
and increased cellular permeability in a time- and concentration-dependent manner. All the above
mentioned factors have in common that the brush border and the production of its associated
enzymes are hampered. These enzymes, such as sucrase, isomaltase, lactulase, enterokinase
and different lipases, are essential for digestion. Especially enterokinase is an essential enzyme
for protein digestion. Enterokinase converts trypsinogen into trypsin, which in turn hydrolysis feed
proteins and activates chymotrypsinogen and carboxypeptidase (Kunitz et al. 1939). In case of
limited enterokinase production a reduced digestion of protein results in more dietary protein as
substrate for the microflora stimulating the growth of proteolytic bacteria.the microbiome of the
intestine is altered into a less favourable one. Protein fermentation results in higher production
of biogenic amines and other toxic N-containing compounds and toxins. Clostridia toxins (α-toxin
and netB toxin) cause necrosis of the intestinal epithelium, whereas lipopolysaccharide (LPS) and
biogenic amines denature claudin, one of the intestinal tight junction proteins. This causes
leakage of protein rich body fluids into the small intestine being substrate for the microflora. LPS
induced cytokines, exert also an indirect effect on feed intake. LPS also may also cause sepsis
in epithelial tissue, resulting in reduced absorption of Na, glucose, chloride and water and is often
associated with diarrhea (Kanno et al., 1996). Guttmann and Finley (2008) suggested that
enteropathogenic E. coli belongs to a family of bacteria called attaching and effacing (A/E)
bacteria. These pathogens excrete proteins directly into the host cells causing a disruption of the
intercellular tight junctions. Another route by which the tight junctions van be disturbed is oxidative
stress which leads to higher expression of pro-inflammatory cytokines. The increased pro-
inflammatory cytokines production resulted in lethargy and direct reduce feed intake. Of the
cytokines ILb1, IL8 and TNF-α are the most determining ones for the reduction of feed intake
(Plata-Salaman, 1998).
Therefore it can be hypothesized, that the addition of feed additives to swine and poultry diets, in
the periods where animals are exposed to the different challenges, might improve intestinal health
and thus reduce physiological negative effects caused by different challenges.

3. Probitics

Most of the health benefits ascribed to the administration of probiotics are linked to modulation of
either host or bacterial factors in the GIT and have been extensively described by Simon et al.
(2001). The utilization of probiotics in numerous studies conducted in swine and poultry have
been linked to improve animal health, increased disease resistance, greater reproductive
performance, enhanced growth promotion and, a better product quality (Simon et al., 2001). But
other studies have reported contrasting results and debate persists as to the true efficacy of
probiotics in swine and poultry (Yeoman and White, 2014). Turner et al. (2005) reviewed 26
papers on probiotic tests in pigs using as response parameters average daily gain (ADG), average
daily feed intake (ADFI), feed conversion ratio (FCR), gut function and immune system activation.
As it is shown in Fig. 2 the greatest response of the probiotic treatment was associated with
improved ADG. In 77% of the experiments the effect of the probiotic treatment on ADFI and
immune system was not reported. An explanation for these results could be that most of the trials
have been conducted for registration purposes and therefore effect on ADG has been the most
interesting parameter. However this result also suggests that there is probably not a direct link
between probiotic treatment in swine and poultry and ADFI stimulation under commercial
conditions. Simon et al. (2001) reported that consistency in improvement of performance in poultry
and swine after a probiotic treatment was much higher under challenge conditions, regardless of
the nature of the challenge parasitic (coccidiosis), microbial (C. perfringens, E. coli, Salmonella),
or simply LPS injection; Ducatelle et al., 2015; Heo et al., 2012), or systemic stressor (increase
or decrease of ambient temperature, transportation, vaccination and overcrowding; Montes and
Pugh, 1993)). Under challenge conditions, an imbalance in the intestinal microbiota is created
and the body defense mechanisms are decreased, which by the supplementation of probiotics,
such problems would be minimized, evidencing differences in the performance results (Ducatelle
et al., 2015). As shown in Fig. 1, an overgrowth in the intestine of some microorganisms, including
enterobacteria has been reported to result in mucosal impairment, villus erosion and damage to
the intestinal cells, thus reducing its nutrients absorptive potential (Pelicano et al., 2005). The
intestinal damage resulted in decreased ADFI and retarded growth as well as suppression of cell-
mediated immune response and low survival (Heo et al., 2012; McDougald, 2003). Burkholder et
al. (2008) reported in broilers that heat stress can affect the body’s defenses and barriers to
bacteria, allowing microbes in the gut to translocate and enter the blood, organs, or other areas
and induce inflammation and other immune responses. On the other hand, in heat-stressed
broilers and pigs, more energy is used to adapt to the stress conditions, therefore less energy will
be used for growth, leading to the decreased growth performance (Lei and Slinger, 1970; Gan et
al., 2013). In addition, deteriorated performance of heat-stressed broilers and pigs can be
attributed to a poor appetite and lower feed intake, which is a defense mechanism to decrease
heat increment of bodies. Based on the literature review it can be suggested two likely positive
effects of probiotics in promoting feed intake in heat-stressed broilers and pigs. The first positive
effect is associated to the prevention of overgrowth of pathogenic bacteria in the intestinal tract
and on maintaining the integrity of the intestinal lining and blocking the movement of pathogenic
microbes from the gut into blood during heat stress; and the second likely positive effect is related
to minimize the problems linked to heat stress.

Finally in humans and rats, have been suggested that exists a bidirectional communication
system between the GIT and the brain. Increasing evidence shows that gut microflora can play a
critical role in this communication; thus, the concept of a gut microflora and brain axis is emerging.
Strong evidence suggests that gut microflora can interact with the central nervous system by
regulating brain chemistry and influencing neuro-endocrine systems associated with stress
response and anxiety. Many of these effects appear to be strain-specific, suggesting a potential
role of certain probiotic strains as novel adjuvant strategy for neurologic disorders (Liu et al.,
2015). Therefore in stress situations such as weaning of piglets, addition of a certain probiotic
strain might reduce the stress associated to weaning and might increase the feed intake of the
piglets immediately after weaning.

Under non-challenging conditions the likely association between probiotics and stimulation or
reduction of feed intake is still in debate.

4. Prebiotics

Beneficial effects of prebiotics are thought to be mediated predominantly through their selective
stimulation of the proliferation of non-pathogenic bacteria that produce short chain fatty acids
(SCFA), such as bifidobacteria, lactobacilli and eubacteria. Therefore the most likely effect of a
given prebiotic tends to be proportional to their fermentability. Young and immature animals have
a physiological limited capacity to ferment prebiotics compared with older and mature animals.
Molist et al. (2009) found that the fermentation capacity of early weaned piglets substantially
increased from day 10 till day 15 post-weaning. The SCFA produced are believed to improve
growth performance and gut health in broilers and pigs. Increased diversity of the intestinal
microflora together with higher intestinal SCFA concentrations and specially butyrate productions
are the main positive effects associated with prebiotic treatment in pigs and broilers (Roberfroid
et al., 2010). Fermentation of prebiotics results in a strong pH reduction, an increased osmotic
effect, a stimulation of the exchange of protons, an increased level of butyrate an enlarged surface
area in the colon may be promising candidates for improving intestinal health (Bongers and
Heuvel, 2003). Butyrate does not pass into the blood but it is directly metabolised by the
colonocytes to maintain metabolic activity and to stimulate the growth of the large intestine
(Montagne et al., 2004). Butyrate has been shown to regulate epithelial cell growth, to induce
differentiation and apoptosis in the small intestine, to increase intestinal cell proliferation in piglets
(Kien et al., 2007) and to improve digestive and absorptive capacities of the small intestine in pigs
(Claus et al., 2007). These effects will lead to lower inflammation associated to a lower intestinal
dysbiosis and greater feed intake of pigs (Hopper et al., 2012). In general it is accepted that a
collateral consequence of the carbohydrate fermentation is the inhibition of the protein
fermentation in the GIT (Awati et al., 2006). Prebiotics and probiotics have proved useful in
improving the overall nitrogen balance by significantly decreasing toxic secondary nitrogen
metabolites (Forsyth et al. 2009).
Torres-Rodriguez et al. (2007) fed 0.1% lactose with or without a probiotic to 10 day old hybrid
turkey hen poults in a commercial house for 26 days. The effect of the probiotic appeared to be
minimal in the absence of lactose, however lactose alone improved body weight by 17% after 28
days. At the end of the experiment, 93 day old hen poults that were fed both lactose and the
probiotic were 436 grams heavier at market weight. This can be explained by the conversion of
lactose into lactic acid in the crop.
A number of studies have demonstrated that SFCAs when infused in the ileum they are able to
produce an ileal brake toward gastric motility and emptying (Cuche et al., 2000). In a study
conducted in pigs Cuche and Malbert (1999) concluded that ileal infusion of SCFA inhibits
gastroduodenal motility. The intensity of this inhibition was related to the molar concentration of
the SCFA. Although this mechanism is not fully understood in pigs, it can be hypothesized that
the inclusion of prebiotics to pigs diet that might lead to a greater concentration of SCFA in the
small and large intestines might result in a delay of the gastric empty which might negatively affect
feed intake of the pigs (Fig. 1). Therefore the likely positive effect of feeding prebiotics could be
more related to a better utilization of the nutrients due to an improvement on the intestinal health
rather than a stimulation of feed intake. Under non-challenge conditions and especially under heat
stress the utilization of prebiotics might be limited in swine and poultry due to the negative relation
between fermentation, heat production and feed intake.

5. Medium chain fatty acids

Medium-chain fatty acids (MCFAs) are saturated and unbranched, with 6–12 carbons, which
occur naturally as medium-chain triglycerides in milk fat and various feed materials like coconut
and palm kernel oil (Dierick et al., 2003; Marten et al., 2006). This group consists of caproic acid
(C6:0, hexanoic acid), caprylic acid (C8:0, octanoic acid) and capric acid (C10:0, decanoic acid).
Also lauric acid (dodecanoic acid) with 12 carbon atoms is also often classed with the group of
MCFAs (Bach and Babayan, 1982). Compared to long-chain fatty acids, MCFAs have a low
melting point and a comparatively high solubility in water. At a neutral pH, the MCFAs are mostly
dissociated (Bach and Babayan, 1982). The hydrolysis of medium chain triglycerides starts in the
oral cavity with the lingual lipases and continues in the stomach where gastric lipases are initially
active against medium chain triglycerides generates significant MCFAs and monoglycerides prior
to release into the duodenum. MCFAs can be utilized directly by the enterocytes for energy
production and thereby help to support the integrity of the intestinal tissue in broilers and piglets
(Guillot et al., 1993). Besides, MCFAs have strong antibacterial effects especially against gram
positive bacteria. Membrane destabilization by the incorporation of MCFAs into the bacterial cell
wall and cytoplasmic membrane, as well as the inhibition of bacterial lipases, which are necessary
for the colonization of the intestinal mucosa, may be the most relevant mechanisms (Bergsson et
al., 2002). However, antibacterial effects of MCFAs depend on the degree of their dissociation.
Their antibacterial effect is generally limited to the stomach and the proximal small intestine
(duodenum), as MCFAs are rapidly absorbed and/or will be only be present in a less active
dissociated form at neutral pH (Zentek et al., 2011). These antibacterial and energy effects have
also been related to positive growth performance results mainly in pigs (Hanczakowska et al.,
2011). In several trials with broilers and pigs a reduction in feed intake was shown when adding
MCFA to the diets (Odle et al., 1991; Decuypere and Dierick, 2003). This effect has been related
to the organoleptic characteristics of the MCFAs (intense goat-like odour of the non-esterified free
fatty acids and the low tolerance to changes in taste (Decuypere and Dierick, 2003)). Furthermore,
the MCFAs can induce the secretion of cholecystokinin and possibly other intestinal hormones,
which influence satiety and therefore feed intake (Mabayo et al., 1992). Coating of the MCFA
might help to overcome these negative feed intake effects as well as increase the bioavailability
of the MCFA to reach the small intestine where they can exert their antibacterial properties.
Although the evidence for the favorable energetic attributes of MCFAs is strong, many authors
consider that the mechanisms resulting in improved broilers and piglet performances are mainly
associated with the antibacterial effects of the MCFAs in the intestinal lumen. This improvement
of the intestinal health might in turn result in a greater growth performance of broilers and piglets.

6. Mycotoxin binders

Since the gastro-intestinal epithelium is the first barrier to come into contact with mycotoxins after
ingestion, several studies have been performed to study the effect of mycotoxins on intestinal
integrity. Most studies have been performed with human intestinal epithelial Caco-2 cells (Caloni
et al., 2002) and the porcine epithelial cell lines IPEC1and IPEC-J2 (Awad et al., 2011). Most
studies with mycotoxins have been performed with either aflatoxins or fusarium toxins, like DON,
T-2 toxin, zearalenone and aflatoxin B1 (AFB1). Pinton et al. (2010), showed that DON directly
affected the expression of tight junction proteins in cultures of IPEC-1 and Caco-2 cell lines
resulting in an increased passage of metabolites from the lumen. They also demonstrated that
the fumonisin B1 (FB1), affected the membranes of IPEC-1 cells, resulting in a greater passage
of this toxin inside the cells.
Goosens et al. (2012), studied the effect of fusarium toxins on epithelial cells observed a dose
related effect of these toxins on cell viability, apoptosis and necrosis. T2-toxin resulted in the most
necrotic cells and was considered the most toxic, whereas both DON and T-2 decreased TEER
and increased cellular permeability for antibiotics, which were used as biomarker.
Bracarense et al. (2011) performed an experiment in which either DON (0.003%) or FB1 (0.006%)
or both were added to piglet diets. The authors observed that piglets that had received these
mycotoxins for a period of 5 weeks showed atrophy and fusion of villi, decreased villi height and
cell proliferation in the jejunum and reduced the number of goblet cells and lymphocytes in the
jejunum. Several cytokines (TNF-α, IL-1β, IL-6, and IL10) were upregulated in jejunum and ileum
indicating a potential negative effect on feed intake.
Aflatoxin is probably the most studied mycotoxin. The major negative effect of this mycotoxin is
on the liver metabolism. However, alflatoxin has also a direct effect on epithelial integrity through
the inhibition of protein synthesis in the enterocytes. Smith et al. (2012) gave a conceptual
overview on how mycotoxins may affect the intestinal integrity and had an effect on both nutrient
intake and growth in swine and poultry (Fig. 3). Jacela et al. (2015) wrote a practical fact sheet in
which they discussed the efficacy of mycotoxin binders. The authors stated that a variety of
substances have the ability to bind mycotoxins. The most commonly used and most researched
mycotoxin-binding agents are the aluminosilicates, clays and zeolites. These are natural
adsorbents that include hydrated sodium calcium aluminosilicates (HSCAS), bentonite and
zeolite. Most of these products are efficient binders of aflatoxins.. Schell et.al, 1993, observed
that contamination of corn reduced the feed intake in pigs. The negative effect could be
counteracted by the addition of 0.5 % bentonite or HSCAS. However, these natural
absorbents have limited or no activity against other types of mycotoxins. Kong et al, 2014,
examined different binders which were highly effective to bind aflatoxin, but they had
limited capacities to bind DON. This agrees with results of Avantaggio e.a., 2005, who
observed low binding capacity to Fusarium toxins.
Other substances with toxin-binding capability include cell-wall components of yeasts. Some
studies have shown that the cell-wall fraction ß-glucan of yeasts such as Saccharomyces
cereviceae can be effective in binding a wide range of mycotoxins. Unlike clays, they can be
added at low levels and are biodegradable. However, research in pigs documenting their efficacy
in mitigating the effects of mycotoxins is limited and has shown inconsistent results. Zhao et al.
(2012) concluded in an experiment conducted with broilers that a HSCAS product effectively
ameliorated the negative effect of AFB1 on growth performance and liver damage, whereas a
yeast cell wall product was less effective especially at AFB1 concentrations of 0.002%. Recently
a fumonisin esterase which hydrolyses FB1 has been registered in EU for pigs (EFSA, 2014).
Although currently sufficient data are not available, it is likely that this enzyme may positively
affect feed intake.

7. Organic acids

The use of organic acids has been reported to positively affect the production of poultry by
competitive exclusion, enhancement of nutrient utilization and growth and feed conversion
efficiency. The organic acids in non-dissociated form can penetrate the bacteria cell wall and
disrupt the normal physiology of certain types of bacteria. Apart from the antimicrobial activity,
they reduce the pH of digesta, increase the pancreatic secretion, and have trophic effects on the
mucosa of the GIT. Acidification with various organic acids has been reported to reduce the
production of toxic components by the bacteria and colonization of pathogens on the intestinal
wall, thus preventing the damage to epithelial cells, also improving the digestibility of proteins,
calcium, phosphorus, magnesium, and zinc, and serve as substrates in the intermediary
metabolism.
In swine an additional mode of action compared to poultry, is the effect on gastric emptying.
Partanen and Mroz (1999) performed a meta-analysis on the effect organic acids in pigs. They
concluded that they effect of addition of feed intake was variable. This could be explained by the
different physico-chemical properties of organic acids and their salts. Most organic acids are used
to improve gastro-intestinal health, but some have additional properties like reducing mold growth
(propionic acid), reducing urine pH and ammonia emission (benzoic acid) or stimulating the
recovery of the intestinal wall (butyrate).
For pigs an important chemical property is the PKa value of the acid. To lower the pH in the
stomach a PKa value lower than 4.5 is of importance. An acid with a higher value will act as a
buffer at lower pH and thus may have a negative effect on the activation of pepsin, which pH
optima at 2 and 3.6 (Kidder, 1976). Organic acids with a low PKa value are formic acid, lactic
acid, fumaric acid and citric acid. Strong organic acids lowered the rate of gastric emptying,
probably due to the larger amount of bicarbonate needed from the pancreatic juices to neutralize
the acidity in the duodenum. The slower gastric emptying will have a positive effect on the
intestinal health since the supply of digesta to the duodenum will be more gradual and the risk of
providing more substrate to the damaged epithelium than the enzymes can hydrolyse is smaller
and thus less substrate will be available for the microflora. A slower gastric emptying may suggest
a lower feed intake. This can be observed at higher incorporation levels. Van der Aar (unpublished
data, 1987) found that addition of more than 2% fumaric acid significantly reduced feed intake in
piglets. However at lower inclusion levels it is counteracted by the positive effect on gastro-
intestinal health. Partanen and Mroz (1999), observed in their analysis in average no effect on
feed intake. If a positive effect was observed it was mostly associated with a greater body weight
of the pigs and therefore a greater feed intake capacity of the pigs.

8. Amino Acids

Crystalline amino acids (AA) are normally not considered feed additives. The additionof crystalline
AA have a direct effect on feed intake and also have specific effects in swine and poultry animals
suffering gastro-intestinal disorders. Diets formulated with high levels of crystalline AA resulted in
lower crude protein levels. Consequently, the amount of undigested protein at the terminal ileum
will be reduced, resulting in less nitrogen substrate for the microflora. Furthermore, AA digestibility
will depend less on the digestive enzymes. Molist et al. (2015) observed greater feed intakes in
both boars and gilts of different genetics housed in pens equipped with individual feeding stations,
when the crude protein content of the diet was reduced from 14.5 to 13.0% with similar ileal
digestible AA levels. Kerr et al. (2003), reported that in growing-finishing pigs the heat production
when pigs were fed low crude protein diets were lower both under thermoneutral and high
temperatures. The authors observed greater feed intakes in both environmental temperatures. In
poultry the effect of crude protein content on feed intake is less clear and at higher environmental
temperatures low protein levels seem to penalize the growth performance (Pereira de Oliveira et
al., 2012).
In farms with poor sanitary conditions in which a greater immune competence of animals is
required specific requirements for AA will emerge. The greater mucin and acute phase proteins
production and immune response lead, relative to Lysine (Lys), to higher requirements for Thr,
Tryptophan and to a lesser extent for sulphur AA (Kampman-van der Hoek, 2015). Star et al.
(2012) reported a more rapid recovery of feed intake in broilers after a coccidiosis- clostridium
challenge, when broilers were fed with a greater Thr/Lys ratio (0.67 vs. 0.63) in the diet. The
Thr/Lys ratio did not affect the severity of the lesions but the feed intake and performance of the
broilers was improved. Another AA that can play an important role in challenge conditions is
glutamic acid. Burrin and Stoll (2009) suggested that glutamic acid stimulates enterocyte
proliferation and is an oxidative fuel for the intestinal wall. By improving the intestinal health also
positive effects on feed intake in swine and poultry are expected.

9. Emulsifiers

Emulsifiers are a wide group of molecules with a hydrophilic and hydrophobic end. This property
stimulates the dispersion of fat molecules in watery solutions. In the GIT they stimulate the
formation of micelles and thus stimulate the digestibility of fats. The effects on growth performance
of adding emulsifiers to swine and poultry diets are inconsistent. The main reason for the variation
in results is the interaction between dietary fat composition (unsaturated vs. saturated fats) and
emulsification. Unsaturated fats disperse better than saturated fats rich in C16:0 and C18:0.
Therefore in diets in which the ratio unsaturated/ saturated fats is larger 2.5 emulsifiers do not
improve digestibility. However, if much saturated fats are used (tallow and palm oil) and the
unsaturated/ saturated ratio is <2.0 emulsifiers may be beneficial to improve fat digestibility and
performance (Doppenberg and van der Aar, 2010). Therefore it can be concluded that emulsifiers
do not have a consistent effect on promoting feed intake in pigs and poultry.

10. Phytogenic feed additives

Phytogenic feed additives are plant derived component, like herbs, spices, essential oils and
saponins. These components have a wide variety of functions, of which some have been known
from their use as medical plants. Phytogenic components affect organoleptic properties of the
feed, which is an important characteristic to improve feed intake of swine, rather than poultry.
They stimulate pancreatic enzyme production (Platel and Srinavasan, 2004), improving nutrient
digestion (Amad et al., 2011); they have direct and indirect antioxidant properties (Müller et al,
2012), reducing fatty acid oxidation in the enterocytes that in turn improves intestinal integrity
(Placha et al. 2014) and hepatic oxidative status (Karadas et al., 2014); and they have anti-
inflammatory properties (Kara et al., 2015). Limiting inflammation indirectly stimulates feed intake
(Fig. 1). Although also antibacterial effects of phytogenic feed additives are described, it should
be realized that their inclusion levels in the feed are generally too low to really substantiate such
effects. However, quorum sensing inhibition in the intestinal tract results in reduced toxin
production (Ahmad et al., 2014). Based on the diverse properties of these phytogenic active
compounds, many papers were published describing the effects of phytogenic feed additives on
production performance of swine and poultry. These effects depend on the botanical source, the
concentration of the active ingredients, the age of the animal, the duration of supply, the feed
composition and the health status of the animal.
Effects of phytogenic feed additives on feed intake of poultry and piglets have been summarised
in Table 1 (Franz et al., 2010). These and other authors (e.g. Brenes and Roura, 2010) reviewed
literature data and indicated in general improved growth rates at similar or lower feed intakes,
when using phytogenic feed additives. This observation clearly indicates improved nutritional
value of the diets via higher digestibility or reduced nutrient repartitioning by anti-oxidant and anti-
inflammatory effects of these additives. Dietary supplementation with thyme oil reduced fatty acid
oxidation in the small intestinal enterocytes of broilers, coinciding with improved Intestinal integrity
(Placha et al., 2014). Others have indicated that reduced feed intakes were temporarily as birds
and pigs have to get used to specific organoleptic characteristics and overall beneficial effects
are mainly evident in the finisher period (Mountzouris et al., 2003).
In young broilers, a nearly significant interaction effect between a phytogenic feed additive
(containing carvacrol, cinnemaldehyde and capsicum) and the composition of the diet was shown,
stimulating feed intake in a corn-based but not in a wheat-based diet. Diets were formulated to be
iso-energetic and iso-nitrogenous (Pirgozliev et al., 2015a). These authors showed that although
the dietary AME content was not affected, the net energy value was significantly improved,
irrespective of diet composition.

11. Anticoccidials

Coccidiosis is an important parasitic disease in poultry that preconditions for intestinal bacterial
infections. These coincidal bacterial infections impact production performance more strongly than
the sole Eimeria infection, due to local or systemic inflammations. Inflammatory processes reduce
feed intake (Fig. 1). Kipper et al. (2013) conducted a meta-analyses based on 69 publications to
quantify the effects of coccidiosis on broiler production performance (Table 2). The authors
concluded that the magnitude of the effects of a coccidiosis infection are dependent on Eimeria
species, bird age, sex and genetics and consequently the effect of anticoccidials. Coccidiosis
prevention is based on the use of chemical and ionophorous anticoccidials, or vaccination against
coccidiosis. Chemical coccidiostats result in a full elimination of some Eimeria species, whereas
ionophores not only eliminates the major part of the Eimeria spp., allowing some immunity, but
also exhibiting antibacterial effects. Effects of ionophorous anticoccidials on production
performance therefore is larger than of chemical products. Kheirabadi et al. (2014) showed that
a clinical coccidiosis infection with a mix of Eimeria spp. reduced feed intake by 20% in the 14-
day period post-infection and 28-day body weight by 25%. Both monensin (an ionophorous
anticoccidial) and Artememisia sieberi could reduce this adverse response to 0-5% (Kheirabadi
et al., 2014).
As resistance against conventional anticoccidials in poultry is increasing, even when using the
rotational and/or shuttle programs of anticoccidials, alternative products are needed to avoid a
reduction in productivity. Vilarino et al. (2009) showed positive effects of an ionophorous
anticoccidial, in broilers fed wheat-based diets (using a low and high viscosity wheat) in a 4-week
performance experiment. Feed intake of broilers was increased by adding the anticoccidial to the
high viscosity wheat diet and reduced the variability of the wheat energy value.
It should be realized that there is a technical consensus that under conditions in which animals
are not challenged with Eimeria species, coccidiostats have a negative effect on feed intake.

12. Feed enzymes

Increased feedstuff costs have resulted in widespread use of feed enzymes, like phytases in.
poultry and swine diets, and carbohydrases, amylases and proteases mainly in poultry diets.
Many papers have shown that phytases stimulate feed intake in pigs and poultry, but that
conclusion is mainly based on comparison to unsupplemented control diets that are not
nutritionally adequate (P-deficiency). Assuming nutritionally adequate diets, feed enzymes can
affect feed intake in different ways:
a. Via degradation of anti-nutritional factors, e.g. phytate, and indigestible soluble
carbohydrates.
b. Via a direct increase in the dietary energy value based on higher nutrient digestibility’s.
c. Via increased digestibility of amino acids.
Degradation of anti-nutritional compounds will generally result in an increased feed intake,
whereas in contrast improved dietary energy value and nutrient digestibility’s will reduce feed
intake based on the assumption that animal eat to meet their nutritional requirements. Therefore,
it is hard to quantify the effects of feed enzymes on feed intake. Pirgozliev et al. (2015b) quantified
the effects of anti-nutritional factors of wheat on daily feed intake in broilers. They calculated that
feed intake in broilers fed wheat-based diets was reduced with increasing wheat pentosan
concentration by 5.5% per % pentosan in wheat. Total pentosan content had a stronger
correlation with feed intake (-0.729) than water soluble pentosans (-0.537) or digesta viscosity (-
0.125). Degrading these anti-nutritional factors might improve feed intake, but the higher dietary
energy value (partly) counteracts this effect.

13. Concluding remarks

Feed additives represent a group of compounds with a wide variation in modes of action. In this
paper we have described the central role of intestinal health on feed intake and the effect of
various additives on intestinal health and intake. The effect on feed intake is for most additives an
indirect effect mediate through improvement of of intestinal health, rather than a direct effect. Due
to the wide variety modes of actions of the feed additives that can result in an improvement of
intestinal health and indirectly on feed intake (like improving intestinal integrity, either by
preventing intestinal damage, compensating for additional nutritional requirements for immune
response, reducing the amount of substrate for the microflora or preventing inflammation) or a
reduction in feed intake (like enzymes to improve dietary energy value or reduced feed intake due
to organoleptic problems associated with non-coated MCFAs and organic acids at high inclusion
levels). It is therefore difficult to conclude on general effects. Since, may additives have an effect
both on reduction of microbial activity and tight junctions , it can be expected that the effects are
not additive. The effect on feed intake in swine and poultry of individual groups of additives is
summarized in Table 3.

Conflict of interest statement

The authors . van der Aar and Molist areas employees of Schothorst Feed Research independent and do
not have any conflict of interest. Dr van der Klis is employed by Delacon, a company that produces and
sells phytogens. The corresponding author has checked the part that is written by him on this specific
topic and has concluded that his contribution was not biassed
References

Ahmad, A., Viljoen, A.M., Chenia, H.Y., 2014. The impact of plant volatiles on bacterial quorum
sensing. Letters in Applied Microbiology 60, 8-19.

Amad, A.A., Maenner, K., Wendler, K.R., Neumann, K., Zentek, J., 2011. Effects of a phytogenic
feed additive on growth performance and ileal nutrient digestibility in broiler chickens. Poultry Sci.
90: 2811-2816.

Avantaggio,A., Solfrizzo, M., Visconti, A., 2005. Recent advances on the use of adsorbent

materials for detoxification of Fusarium mycotoxins. Food Addit. Contam. 22, 379-388.

Awad, W.A., Aschenbach, J.R., Zentek, J., 2011. Cytotoxicity and metabolic stress induced by
deoxynivalenol in the porcine intestinal IPEC-J2 cell line. J. Anim. Physiol. Anim. Nutr. 96: 717-
724.

Awati, A., Williams, B.A., Bosch, M.W., Gerrits, W.J.J., Verstegen, M.W.A., 2006. Effect of
inclusion of fermentable carbohydrates in the diet on fermentation end product profile in feces
of weanling piglets. J. Anim. Sci. 84, 2133-2140.
Bach, A.C., Babayan, V.K., 1982. Medium-chain triglycerides: an update. Am. J. Clin. Nutr. 36,
950-962.
Beers-Schreurs Van, H.G.M., 1996. The changes in the function of the large intestine of weaned
pigs. Ph.D. thesis. Univ. of Utrecht, The Netherlands.
Bergsson, G., Steingrímsson, Ó., Thormar, H., 2002. Bactericidal effects of fatty acids and
monoglycerides on Helicobacter pylori. Int. J. Antimicrob. Agents 20, 258-262.
Bongers, A., van der Huevel, E.G.H.M., 2003. Prebiotics and the bioavailability of mineral and
trace elements. Food Rev. Int. 19, 397-422.
Bracarense, A.P., Lucioli, J., Grenier, B., Pacheco, G.D., Moll, W.D., Schatzma, Y.R.G., Oswald,
I.P., 2012. Chronic ingestion of deoxynivalenol and fumonisin, alone or in interaction, induces
morphological and immunological changes in the intestine of piglets. Br. J. Nutr. 107, 1776–
1786.
Brenes, A., Roura, E., 2010. Essential oils in poultry nutrition: Main effects and modes of action.
Anim Feed Sci. Technol. 158, 1-14.
Burkholder, K.M., Thompson, K.L., Einstein, M.E., Applegate, T.J., Patterson, J.A., 2008.
Influence of stressors on normal intestinal microbiota, intestinal morphology, and
susceptibility to Salmonella Enteritidis colonization in broilers. Poult. Sci. 87, 1734-1741.
Burrin, D.G., Stoll, B., 2009. Metabolic fate and function of dietary glutamate in the gut. Am. J.
Clin. Nutr. 90, 850S-856S.
Caloni, F., Spotti, M., Pompa, G., Zucco, F., Stammati, A., De Angelis, I., 2002. Evaluation of
fumonisin B(1) and its metabolites absorption and toxicity on intestinal cells line Caco-2.
Toxicon 40, 1181-1188.
Carvajal, O., Nakayama, M., Kishi, T., Sato, M., Ikeda, I., Sugano, M., Imaizumi, K., 2000. Effect
of medium-chain fatty acid positional distribution in dietary triacylglycerol on lymphatic lipid
transport and chylomicron composition in rats. Lipids 35, 1345-1351.
Claus, R., Günthner, D., Letzgub, H., 2007. Effects of feeding fat-coated butyrate on mucosal
morphology and function in the small intestine of the pig. J. Anim. Physiol. Anim. Nutr. 91,
312-318.
Cuche, G., Cuber, J.C., Malbert, C.H., 2000. Ileal short-chain fatty acids inhibit gastric motility by
a humoral pathway. Am. J. Physiol. Gastrointest. Liver Physiol. 279, G925-G930.
Cuche, G., Malbert, C.H., 1999. Ileal short-chain fatty acids inhibit transpyloric flow in pigs. Scand.
J. Gastroenterol. 34, 149-155.
Dierick, N.A., Decuypere, J.A., Degeyter, I., 2003. The combined use of whole Cuphea seeds
containing medium chain fatty acids and an exogenous lipase in piglet nutrition. Arch. Anim.
Nutr. 57, 49-63.
Decuypere, J.A., Dierick, N.A., 2003. The combined use of triacylglycerols containing medium-
chain fatty acids and exogenous lipolytic enzymes as an alternative to in-feed antibiotics in
piglets: concept, possibilities and limitations. An overview. Nutr. Res. Rev. 16, 193-210.
Doppenberg, J., van der Aar, P.J., 2010. Facts about fats: a review of the feeding value of fats
and oils in feeds for swine and poultry. Cab direct, the Netherlands.
Ducatelle, R., Eeckhaut, V., Haesebrouck, F., Van Immerseel, F., 2015. A review on prebiotics
and probiotics for the control of dysbiosis: present status and future perspectives. Animal 9,
43-48.
Elsasser, T.H., Kahl, S., Rumsey, T.S., Blum, J.W., 2000. Modulation of growth performance in
disease: reactive nitrogen compounds and their impact on cell proteins. Domest. Anim.
Endocrinol. 19, 75-84.
Ferket, P.R., Gernat, A.G., 2006. Factors that affect feed intake of meat birds: a review. Int.
J. Poult. Sci. 5, 905-911.
Forsyth, C.B., Farhadi, A., Jakate, S.M., Tang, Y., Shaikh, M., Keshavarzian, A., 2009.
Lactobacillus GG treatment ameliorates alcohol-induced intestinal oxidative stress, gut
leakiness, and liver injury in a rat model of alcoholic steatohepatitis. Alcohol. 43, 163-172.
Franz, C., Baser, K.H.C., Windisch, W., 2010. Essential oils and aromatic plants in animal feeding
– a European perspective. A review. Flav. & Frag. J. 25, 327-340.
Gan, F., Ren, F., Chen, X., Lv, C., Pan, C., Ye, G., Shi, J., Shi, X., Zhou, H., Shituleni, S.A.,
Huang, K., 2013. Effects of selenium-enriched probiotics on heat shock protein mRNA levels
in piglet under heat stress conditions. J. Agric. Food Chem. 13, 2385-2391.
Goossens, J., Vandenbroucke, V., Pasmans, F., De Baere, S., Devreese, M., Osselaere, A.,
Verbrugghe, E., Haesebrouck, F., De Saeger, S., Eeckhout, M., Audenaert, K., Haesaert, G.,
De Backer, P., Croubels, S., 2012. Influence of mycotoxins and a mycotoxin adsorbing agent
on the oral bioavailability of commonly used antibiotics in pigs. Toxins 4, 281-295.
Guillot, B., Vaugelade, P., Lemarchal, P., Rerat, A., 1993. Intestinal absorption and liver uptake
of medium-chain fatty acids in non-anaesthetized pigs. Br. J. Nutr. 69, 431-442.
Guttman, J.A., Finlay, B.B., 2009. Tight junctions as targets of infectious agents. Biochim.
Biophys. Acta - Biomembranes 1788, 832–841.
Hampson, D.J., Hinton, M., Kidder, D.E., 1985. Coliform numbers in the stomach and small
intestine of healthy pigs following weaning at three weeks of age. J. Comp. Path. 95, 353-
362.
Hanczakowska, E., Szewczyk, A., Okoṅ, K., 2011. Effects of dietary caprylic and capric acids on
piglet performance and mucosal epithelium structure of the ileum. J. Anim. Feed Sci. Technol.
20, 556-565.
Heo, J.M., Opapeju, F.O., Pluske, J.R., Kim, J.C., Hampson, D.J., Nyachoti, C.M., 2013.
Gastrointestinal health and function in weaned pigs: a review of feeding strategies to control
post-weaning diarrhoea without using in-feed antimicrobial compounds. Anim. Physiol. Anim.
Nutr. 97, 207-237.
Hopper, L.V., Littman, D.R., Macpherson, A.J., 2012. Interactions between the microbiota and the
immune system. Science. 336, 1268-1273.
Jacela, J.Y., DeRouchey, J.M., Tokach, M.D., 2010. Feed additives for swine: Fact sheets –
flavors and mold inhibitors, mycotoxin binders, and antioxidants. J. Swine Health Prod. 18,
27–32.
Jansman, A.J.M, Verstegen, M.W.A., Huisman, J., 1993. Effects of dietary inclusion of hulls of
faba beans (Vicia faba L.) with a low and high content of condensed tannins on digestion and
some physiological parameters in piglets Anim. Feed Sci. Technol. 43, 239-257.
Kampman-van der Hoek, E., 2015. Impact of health status on amino acid requirements of growing
pigs, Ph.D. Thesis Wageningen University, Wageningen, The Netherlands.
Kanno, S., Emil, S., Kosi, M., Monforte-Munoz, H., Atkinson, J.,1996. Small intestinal absorption
during endotoxemia in swine. Am. Surg. 10, 793-799.
Kara, M., Uslu, S., Demirci, F., Temel, H.E., Baydemir, C., 2014. Supplemental carvacrol can
reduce the severity of inflammation by influencing the production of mediators of
inflammation. Inflammation 38, 1020-1027.

Karadas, F., Pirgozliev, V., Rose, S.P., Dimitrov, D., Oduguwa, O., Bravo, D., 2014. Dietray
essential oils improve the hepatic antioxidative status of broiler chickens. Br. Poult. Sci. 55,
329-334.
Kerr, B.J., Southern, L.L., Bidner, T.D., Friesen, K.G., Easter, R.A., 2003. Influence of dietary
protein level, amino acid supplementation, and dietary energy levels on growing-finishing pig
performance and carcass composition. J. Anim. Sci. 81, 3075-3087.
Kheirbadi, K.P., Katadj, J.K., Bahadoran, S., Teixeira da Silva, J.A., Samani, A.D., Bashi, M.C.,
2014. Comparison of the anticoccidial effect of granulated extract of Artemisia sieberi with
monensin in experimental coccidiosis in broiler chickens. Experimen. Parasitol. 141, 129-
133.
Kidder, D.E., Manners, M.J., 1978. Digestion in the Pig. Scientechnica Bristol.
Kien, C.L., Blauwiekel, R., Bunn, J.Y., Jetton, T.L., Frankel, W.L., Holst, J.J., 2007. Cecal infusion
of butyrate increases intestinal cell proliferation in piglets. J. Nutr. 137, 916-922.
Kipper M., Andretta, I., Lehnen, C.R., Lovatto, P.A., Monteiro, S.G., 2013. Meta-analysis of the
performance variation in broilers experimentally challenged by Eimeria spp. Vet Parasitol. 196,
77-84.
Kong, C. Shin, Y.S. , Kim, B.G. 2014, Evaluation of mycotoxin sequestering agents for aflatoxin
and deoxynivalenol: an in vitro approach, Springerplus 3: 346- 349.
Koninkx, J.F., Hendriks, H.G., van Rossum, J.M., van den Ingh, T.S., Mouwen, J.M., 1992.
Interaction of legume lectins with the cellular metabolism of differentiated Caco-2 cells.
Gastroenterol. 102,1516-1523.
Kunitz, M., 1939.Formation of trypsin from crystalline trypsinogen by means of enterokinase. J.
Gen. Physiol. 22, 429–446.
Lei, K.Y., Slinger, S.J., 1970. Energy utilization in the chick in relation to certain environmental
stresses. Can. J. Anim. Sci. 50, 285–292.
Liu, X., Cao, S., Zhang, X., 2015. Modulation of gut microbiota-brain axis by probiotics, prebiotics
and diet. J. Agric. Food Chem. 63, 7885-7895.
Mabayo, R.T., Furuse, M., Yang, S.-I., Okumura, J.-I., 1992. Medium-chain triacylglycerols
enhance release of cholecystokinin in chicks. J. Nutr. 122, 1702-1705.
Marten, B., Pfeuffer, M., Schrezenmeir, J., 2006. Medium-chain triglycerides. (Special issue:
Technological and health aspects of bioactive components of milk.). Int. Dairy J. 16, 1374-1382.
McDougald, L.R., 2003. Coccidiosis. In: Saif, Y.M. (Ed.), Diseases of Poultry. Iowa State
University Press, Ames, pp. 974-991.
Miller, D., Johnston, Z., Mullan, B., Pluske, J., Hansen, C., 2009. Nutritional manipulation of the
somatotropic axis in grower and finisher pigs. Report prepared for the Co-operative Research
Centre for an Internationally Competitive Pork Industry, Australia.
Moeser, A.J., Klok, C.V., Ryan, K.A., Wooten, J.G., Little, D., Cook, V.L., Blikslager, A.T., 2007.
Stress signaling pathways activated by weaning mediate intestinal dysfunction in the pig. Am.
J. Physiol. Gastrointest. Liver Physiol. 292, G173–G181.
Molist, F., Gómez de Segura, A., Gasa, J., Hermes, R.G., Manzanilla, E.G., Anguita, M., Pérez,
J.F., 2009. Effects of the insoluble and soluble dietary fibre on the physicochemical properties
of digesta and the microbial activity in early weaned piglets. Anim. Feed Sci. Technol. 149,
346-353.
Molist. F, Pijlman J., van der Aar, P., Rovers, M., Ensink, J., Corrent, E., 2015. Effect of low
protein diet composition on growth performance and carcass characteristics. In: Proceedings
of the 13th Digestive Physiology in Pigs Symposium, Kliczkow, Poland, p. 170.
Montagne, L., Cavaney, F.S., Hampson, D.J., Lallès, J.P., Pluske, J.R., 2004. Effect of diet
composition on postweaning colibacillosis in piglets. J. Anim. Sci. 82, 2364-2374.
Montes, A.J., Pugh, D.G., 1993. The use of probiotics in food-animal practice. Vet. Med. 88, 282-
288.
Mountzouris, K.C., Paraskevas, V., Tsirtsikos, P., Palamidi, I., Steiner, T., Schatzmayr, G.,
Fegeros, K., 2011. Assessment of a phytogenic feed additive effect on broiler growth
performance, nutrient digestibility and caecal microflora composition. Anim. Feed Sci.
Technol. 168, 223-231.
Müller, K., Blum, N.M., Kluge, H., Muller, A.S., 2012. Influence of broccoli and various essential
oils onperformance and expression of xenobiotic- and antioxidant enzymes in broiler
chickens. Br. J. Nutr. 108, 588-602.
Odle, J., Benevenga, N.J., Crenshaw, T.D., 1991. Utilization of medium-chain triglycerides by
neonatal piglets: chain length of even- and odd-carbon fatty acids and apparent
digestion/absorption and hepatic metabolism. J. Nutr. 121, 605–614.
Partanen, K.H., Mroz, Z.,1999. Organic acids for performance enhancement in pig diets. See
comment in PubMed Commons belowNutr. Res. Rev. 12, 117-145.
Pelicano, E.R.L., Souza, P.A., Souza, H.B.A., Figueiredo, D.F., Boiago, M.M., Carvalho, S.R.,
Bordon, B.F., 2005. Intestinal mucosa development in broiler chickens fed natural growth
promoters. Braz. J. Poult. Sci. 7, 221-229.
Pereira de Oliveira, W., Flávia Miranda de Oliveira, R., Lopes Donzele, J., Rodrigues de Oliveira
Neto, A., Gomes, P.C., de Assis Maia, A.P., Reis Furtado Campos, P.H., Gasparino, E.,
2013. Dietary crude protein reduction on growth and carcass performance of 22 to 42-day-
old broilers reared under different temperatures, R. Bras. Zootec. 42, 599-604.

Pinton, P., Braicu, C., Nougayrede, J.P., Laffitte, J., Taranu, I., Oswald, I.P., 2010. Deoxynivalenol
impairs porcine intestinal barrier function and decreases the protein expression of claudin-4
through a mitogen-activated protein kinase-dependent mechanism. J. Nutr. 140, 1956-1962.
Placha, I., Takacova, J., Ryzner, M., Cobanova, K., Laukova, A., Strompfova, V., Venglovska, K.,
Faix, S., 2014. Effect of thyme essential oil and selenium on intestine integrity and anti-
oxidant sattus of broilers. Br. Poultry Sci. 55, 105-114.
Plata-Salaman, C.R., Peloso, E., Satinoff, E., 1998. Cytokine-induced fever in obese ( fa/fa) and
lean (Fa/Fa) Zucker rats. Am. J. Physiol. 275, R1353.
Platel, K., Srinivasan, K., 2004. Digestive stimulant action of spices: A myth or reality? Indian J.
of Med. Res. 119, 167-179.
Pirgozliev, V., Beccaccia, A., Rose, S.P., Bravo, D. 2015a. Partitioning of dietary energy of
chickens fed maize- or wheat-based diets with and without a commercial blend of phytogenic
feed additives. J. Anim. Sci. 93, 1695-1702.
Pirgozliev, V., Rose, S.P., Pellny, T., Amerah, A.M., Wickramasinghe, M., Ulker, M., Rakszegi,
M., Bedo, Z., Shewry, P.R., Lovegrove, A., 2015b. Energy utilization and growth performance
of chickens fed novel wheat inbred lines selected for different pentosan levels with and
without xylanase supplementation. Poult. Sci. 94, 232-239.
Roberfroid, M., Gibson, G.R., Hoyles, L., McCartney, A.L., Rastall, R., Rowland, I.,Wolvers, D.,
Watzl, B., Szajevska, H., Stahl, B., Guarner, F., Respondek, F., Whelan, K., Coxam, V.,
Davicco, M.J., Leotoing, L., Wittrant, Y., Delzenne, N.M., Cani, P.D., Neyrinck, A.M.,
Meheust, A. 2010. Prebiotic effects: metabolic and health benefits. Br. J. Nutr. 104, S1–S63.
Schell TC, Lindemann MD, Kornegay ET, Blodgett DJ, Doerr JA.,1993,Effectiveness of different
types of clay for reducing the detrimental effects of aflatoxin-contaminated diets on performance
and serum profiles of weanling pigs.
J Anim Sci. ,5,:1226-31
Simon, O., Jadamus, A., Vahjen, W., 2001. Probiotic feed additives–effectiveness and expected
modes of action. J. Anim. Sci. 10, 51-67.
Solis de los Santos, F., Donoghue, A.M., Venkitanarayanan, K., Dirain, M.L., Reyes-Herrera, I.,
Blore, P.J., Donoghue, D.J., 2008. Caprylic acid supplemented in feed reduces enteric
campylobacter jejuni colonization in ten-day-old broiler chickens. Poult Sci. 87, 800-804.
Star, L., Rovers, M., Corrent, E., van der Klis, J.D., 2012. Threonine requirement of broiler
chickens during subclinical intestinal Clostridium infection. Poult. Sci. 91, 643-652.
Torres-Rodriguez, A., Higgins, S.E., Vicente, J.L.S., Wolfenden, A.D., Gaona-Ramirez, G.,
Barton, J.T., Tellez, G., Donoghue, A.M., Hargis, B.M., 2007. Effect of lactose as a prebiotic
on turkey body weight under commercial conditions. J. Appl. Poult. Res. 16, 635-641.
Turner, J.L., Dritz, P.S.S., Minton, J.E., 2001. Review: Alternatives to conventional antimicrobials
in swine diets. Prof. Anim. Sci. 17:217-226.
Vilarino, M., Skiba, F., Gauzere, J.M., Metayer, J.P., 2009. The energy value of wheat at high-
viscosity in the broilers feed is less variable with addition of a coccidiostat. In: Proceedings
of the 8th Avian French Research Days, St Malo, France.
Yeoman, C.J., White, B.A., 2014. Gastrointestinal tract microbiota and probiotics in production
animals. Annu. Rev. Anim. Biosci. 2, 469-486.
Younes, H., Alphonse, J.C., Hadj-Abdelkader, M., Rémésy, C., 2001. Fermentable carbohydrate
and digestive nitrogen excretion. J. Ren. Nutr. 11, 139-148.
Zhao, J., Shirley, R.B., Dibner, J.D., Uraizee, F., Officer, M., Kitchell, M., Vazquez-Anon, M.,
Knight, C.D., 2010. Comparison of hydrated sodium calcium aluminosilicate and yeast cell
wall on counteracting aflatoxicosis in broiler chicks. Poult. Sci. 89, 2147-56.
Zentek, J., Buchheit-Renko, S., Ferrara, F., Vahjen, W., Van Kessel, A.G., Pieper, R., 2011.
Nutritional and physiological role of medium-chain triglycerides and medium-chain fatty acids
in piglets. Anim. Health Res. Rev. 12, 83-93.
 Fig. 1. Relation between casual factors initiated by feed components, infections and/ or stress

and changes at the instestinal and systemic level that lead to low feed intake of the animals.
 90.0
80.0
70.0
60.0
50.0
40.0
30.0
20.0
10.0
0.0
ADG ADFI FCR Gut function Immune system

0 + x

Fig. 2. Likely relative (%) positive effects (0, no effects; +, positive effects; x, not reported

effects) of probiotics inclusion in pigs using as response parameters: average daily gain (ADG), average

daily feed intake (ADFI), feed conversion ratio (FCR), gut function and immune system stimulation.

Adapted from Turner et al. (2005).

 Figure 3. A conceptual framework for the effect of mycotoxin exposure on growth retardation

(adapted from Smith et al., 2012). 1, aflatoxin, 2, deoxynivalenol, 3, fumonisin.

Table 1. Effects of aromatic herbs and essential oils as feed additives on feed intake in piglets
and broilers (adapted from Franz et al., 2010).
Dietary dose Piglets Dietary dose Broilers
(g/kg) (% reduction) (g/kg) (% reduction)
Essential oils
Anise 0.15 -1
Caraway 0.1 -9/-2
Carvacrol 0.2 +2
Cinnamaldehyde 0.1 -2
Cinnamon 0.1 -5/+5 0.1 -4
Clove 0.1 +1/+3 0.1 -3
Fennel 0.1 +3
Lemongrass 0.1 -3 0.1 +1
Oregano 0.1/0.5 -3/+12 0.1/0.15/0.3/1.0 -6/+3
Peppermint 0.1 -9 0.1 -3
Pimento 0.1 -8
Rosemary 0.15/0.3 0/-2
Thymol 0.1/0.2 +1/-5
Herbs and spices
Coriander 2.0 +4
Garlic 1.0 -7/+5 1.0 -5
Hops 0.25 +2
Oregano 2.0 -1/+4 5.0 +5
Sage 2.0 +3
Thyme 1.0/2.0/5.0 -1/+4 1.0 0/+1
Yarrow 2.0 +1
Table 2. Adjusted means of feed intake, weight gain and feed conversion ratio (FCR) in broilers
experimentally infected with Eimeria spp. (adapted from Kipper et al., 2013).
Feed intake Weight gain FCR
(g/day) (g/day)
Control 66.8b 43.6a 1.57b
E. acervulina 57.1b (85%) 40.1b (92%) 1.77b (113%)
E. maxima 72.1a (108%) 33.6c (77%) 3.78a (241%)
E. tenella 55.3b (83%) 38.4bc (88%) 2.33ab (148%)
Pooled infection 70.0a (105%) 39.3bc (90%) 1.71b (109%)
RSD 9.5 8.7 1.12
a,b,c
values with different superscript letter in the same column differ (P<0.001) by Tukey
test; Value s between brackets are relative change compared to the uninfected control
Table 3. Summary of the feed intake effects (+, positive effect on feed intake; 0, no effect on
feed intake; -, negative effect on feed intake) in swine and poultry of the different feed additives.

Feed additive ++ + 0 -

Probiotics x1

Prebiotics x1

Medium chain fatty acids x

Mycotoxin binders x1

Organic acids x1

Amino acids x

Emulsifiers x

Phytogenic feed additives x1

Anticcocidiostats x1

Feed enzymes x

x1 indirect effect due to improvement of the health status of the animals.