Review: Are we using probiotics correctly in post-weaning piglets?

Abstract

Intensive farming may involve the use of diets, environments or management practices that impose physiological and psychological stressors on the animals. In particular, early weaning is nowadays a common practice to increase the productive yield of pig farms. Still, it is considered one of the most critical periods in swine production, where piglet performance can be seriously affected and where they are predisposed to the overgrowth of opportunistic pathogens. Pig producers nowadays face the challenge to overcome this situation in a context of increasing restrictions on the use of antibiotics in animal production. Great efforts are being made to find strategies to help piglets overcome the challenges of early weaning. Among them, a nutritional strategy that has received increasing attention in the last few years is the use of probiotics. It has been extensively documented that probiotics can reduce digestive disorders and improve productive parameters. Still, research in probiotics so far has also been characterized as being inconsistent and with low reproducibility from farm to farm. Scientific literature related to probiotic effects against gastrointestinal pathogens will be critically examined in this review. Moreover, the actual practical approach when using probiotics in these animals, and potential strategies to increase consistency in probiotic effects, will be discussed. Thus, considering the boost in probiotic research observed in recent years, this paper aims to provide a much-needed, in-depth review of the scientific data published to-date. Furthermore, it aims to be useful to swine nutritionists, researchers and the additive industry to critically consider their approach when developing or using probiotic strategies in weaning piglets.

Full text

Review: Are we using probiotics correctly in post-weaning piglets?
E. Barba-Vidal
†
, S. M. Martín-Orúe and L. Castillejos
Animal Nutrition and Welfare Service, Departament de Ciència Animal i dels Aliments, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain
(Received 22 November 2017; Accepted 26 March 2018; First published online 3 May 2018)
Intensive farming may involve the use of diets, environments or management practices that impose physiological and psychological
stressors on the animals. In particular, early weaning is nowadays a common practice to increase the productive yield of pig farms.
Still, it is considered one of the most critical periods in swine production, where piglet performance can be seriously affected and
where they are predisposed to the overgrowth of opportunistic pathogens. Pig producers nowadays face the challenge to overcome
this situation in a context of increasing restrictions on the use of antibiotics in animal production. Great efforts are being made to
find strategies to help piglets overcome the challenges of early weaning. Among them, a nutritional strategy that has received
increasing attention in the last few years is the use of probiotics. It has been extensively documented that probiotics can reduce
digestive disorders and improve productive parameters. Still, research in probiotics so far has also been characterized as being
inconsistent and with low reproducibility from farm to farm. Scientific literature related to probiotic effects against gastrointestinal
pathogens will be critically examined in this review. Moreover, the actual practical approach when using probiotics in these
animals, and potential strategies to increase consistency in probiotic effects, will be discussed. Thus, considering the boost in
probiotic research observed in recent years, this paper aims to provide a much-needed, in-depth review of the scientific data
published to-date. Furthermore, it aims to be useful to swine nutritionists, researchers and the additive industry to critically
consider their approach when developing or using probiotic strategies in weaning piglets.
Keywords: feed additive, gut health, antibiotic alternative, nutrition, swine
Implications
This review critically examines the use of probiotics in
post-weaning piglets, focusing on challenge situations, and
proposes potential strategies to increase consistency in
probiotic effects. Given the current lack of reproducibility
commonly described with probiotic use, this approach could
have significant positive effects upon the efficacy of probiotic
products and economic viability of the swine industry.
Introduction
In intensive farming systems, piglets are weaned at much
earlier ages (between 3 and 5 weeks) than are those that
would be expected in a natural environment (around
17 weeks (Jensen and Recén, 1989)). This early weaning
situation is considered one of the most critical periods in swine
production, in which the animals have to face multiple stres-
sors. Piglets undergo complex social changes, such as
separation from their mothers and littermates (Pluske
et al
.,
1997). In addition, they have to adapt to abrupt changes in
the feed regime and in the environment (Weary
et al
., 2008),
leading to a variable period of hypo- or anorexia (Bruininx,
2001). All of this happens at a time when the animals still
have an immature immune system (Lallès
et al
., 2004), low
thermoregulation (Le Dividich and Herpin, 1994) and digestive
capacities (Lallès
et al
., 2007a), together with unstable intest-
inal microbiota (Wang
et al
., 2013). Weaning is, therefore,
a time where the performance of the pigs is seriously affected
(Lallès
et al
., 2007b), and where piglets are predisposed to
the overgrowth of opportunistic pathogens like
Salmonella
or
Escherichia coli
(Pluske
et al
., 1997; Fouhse
et al
., 2016).
Altogether, the process is known as a post-weaning syndrome
and has been extensively studied and reviewed (Pluske
et al
.,
1997; Lallès
et al
., 2007a; Heo
et al
., 2013).
The traditional approach to overcome this situation has
been the use of in-feed antibiotics. However, in Europe, the
use of antibiotics as growth promoters has been banned
(Regulation (EC) No. 1831/2003), and worldwide authorities
are also pressing to limit its therapeutic use (National Pork
Board, 2015; European Food Safety Authority and European
Medicines Agency, 2017). With this context, the pig industry
and researchers are making great efforts in trying to find
†
Present address: Department of Animal and Poultry Science, University of
Saskatchewan, Saskatchewan, Canada S7N 5A8. E-mail: emili.barba.vidal@
gmail.com
Animal
(2018), 12:12, pp 2489–2498 © The Animal Consortium 2018
doi:10.1017/S1751731118000873
animal
2489

biosecurity (Madec
et al
., 2000), management (Weary
et al
.,
2009; Heo
et al
., 2013), genetic (Lunney, 2007) and feeding
(Pluske
et al
., 2002; Lallès
et al
., 2007b) strategies to help
piglets overcome the challenges of weaning. Among them,
a nutritional strategy that has received increasing attention
in recent years is the use of probiotics. It has been extensively
documented that probiotics can reduce digestive disorders
and improve productive parameters (Ahasan
et al
., 2015;
Bajagai
et al
., 2016). Still, research in probiotics so far has
been characterized as being inconsistent and with low
reproducibility from farm to farm. Consequently, although
probiotics have demonstrated good potential, many farmers
do not consider them to be reliable.
The objective of this review is to critically examine the use
of probiotics in the post-weaning phase, focusing on chal-
lenge situations, in order to assess whether we are making
good use or not of these types of products. Thus, scientific
literature related to probiotic effects in experimental models
of disease will be reviewed, and subsequently, a discussion
about the actual practical approach when using probiotics
and how it could be improved will be presented.
Considering the boost in probiotic research observed in the
last few years, this paper aims to provide a much-needed,
in-depth review of the scientific data published to-date.
Furthermore, it aims to be useful to swine nutritionists,
researchers and the additive industry to critically consider
their approach when using or developing probiotic strategies
in post-weaning piglets.
Use of probiotics against pathogens
A vast amount of research is published yearly in relation to
probiotic capacities to improve gastrointestinal health and
fight digestive pathogens. It is worth mentioning that the
interest of finding probiotic strategies to fight these
pathogens not only exists in animal production, but it is also
present in human medicine, which, in many cases, uses pigs
as a
One Health
approach (Mardones
et al
., 2017) or as a
human model of disease (Meurens
et al
., 2012). This fact
enriches the amount of information available and may be
useful for the pig industry. Table 1 recalls main scientific
studies published to-date, assessing the use of probiotics
against pathogens in piglet experimental models of disease.
Limits on therapeutic use of probiotics
The first important factor observed is that many authors
reported a positive effect by using probiotics, but there is also
a considerable amount of research not supporting their use
in a disease situation. In general terms, there is a higher
number of articles describing beneficial effects with the use
of probiotics (>80%) rather than negative effects. However,
we must consider that we may have a positive-outcome bias,
as many times there may not be industrial interest to publish
neutral or negative results (Fanelli, 2012). Still, in view of the
current published data, it can be concluded that in the
majority of cases probiotic effects against pathogens were
positive, although they tended to be rather discrete.
Spectacular improvements, such as eliminating pathogen
excretion or important increases in productive parameters
have not been reported. Hence, with this background, a first
takeaway message would be to stop looking for probiotics as
direct replacements for antibiotics, as their effects are not
comparable. Alternatively, as proposed by the European
Food Safety Authority, probiotics should be considered as
zoo-technical additives, in the category of digestibility
enhancers or gut flora stabilizers (European Food Safety
Authority, 2007). This change of mindset implies that,
although with probiotics we may potentially target the same
objectives than with antibiotics, when using probiotics our
approach should be different. In other words, we should not
include a probiotic and expect the same effects than with an
antibiotic on its own, but we should combine them
with other feed and/or management strategies with a more
holistic approach.
Uncertainties around probiotics effects
Another apparent aspect of the reported results is that it is
extremely difficult to discuss and extract conclusions with the
data reported to-date because the conditions in which the
probiotics have been tested are highly variable. There are
important differences in experimental factors such as piglet
days of age, treatment concentrations and dosing methods,
or other aspects not reflected in Table 1, such as genetics,
sanitary status, treatment days or diets. Probiotic effects are
known to be treatment specific, depending on the particular
strain, dose and context (Bosi and Trevisi, 2010; Li
et al
.,
2012), and host specific, depending on host-related physio-
logical parameters (e.g. health status and genetics) or
environment (e.g. sanitary status and diet) (Collado
et al.
,
2007; Mulder
et al
., 2009; Dinan and Cryan, 2016). Thus, it
would be possible that probiotic strains that were not used in
a certain trial turned out to be useful in another one, or vice
versa. Undoubtedly, this background of uncertainty has
made probiotics to be regarded as untrustworthy, being one
of the main reasons preventing them from being widespread
in the swine industry (Bosi and Trevisi, 2010). A first
approach to reduce this variability could be to standardize
conditions in which probiotics are studied to have tight
control of the variables. However, although this strategy may
potentially increase consistency in probiotic research, this
would preclude even more the extrapolations of scientific
results to the wide array of real-life situations present in pig
production. Finally, another approach would be to increase
basic research to investigate in-depth the physiological
reasons for this variability, with the aim of developing
tailored strategies to each situation.
Potential risks of probiotics
Furthermore, another important point is that results shown in
Table 1 suggest that there may be potential risks when using
certain probiotics in animals with damaged gut health or
pathogen pressure. It has been documented in scientific
literature that a baseline of bacterial translocation, possibly
due to the increased para/trans-cellular permeability in the
Barba-Vidal, Martín-Orúe and Castillejos
2490

Table 1
Pig
in vivo
scientific works evaluating the use of probiotics against digestive bacterial pathogens (
Escherichia coli
and
Salmonella
sp.)
Probiotic Pathogen Animals
References Strain, dose per pig and dosing method Strain and dose per pig
Days old: weaning
→Inoculation Benefits Main results
De Cupere
et al
. (1992) (a)
Bacillus cereus var. Toyoi
(1 ×10
9
cfu/g)
(b)
Lactobacillus
spp. (7.5 ×10
7
cfu/g)
(c)
Streptococcus faecium
(5.6 ×10
8
cfu/g)
Included in feed
Escherichia coli
0141 K85 (10
9
cfu) 28 →30 No No improvements on clinical symptoms or mortality.
No improvements on fecal
E. coli
shedding
Shu
et al
. (2001)
Bifidobacterium lactis
HN019 (10
9
cfu/day)
Oral administration
E. coli
sp. 21 →natural
acquisition
Yes Reduced diarrhea scores and fecal shedding of
E. coli.
Improved animal performance. Increased T-cell
differentiation and pathogen-specific antibody titers
Bhandari
et al
. (2008)
Bacillus subtilis
(6 ×10
8
cfu/kg)
Included in feed
E. coli
K88 (4 ×10
10
cfu) 17 →24 Yes Reduced diarrhea scores and mortality. Modulated
microbial diversity.
Lessard
et al
. (2009) (a)
Pediococcus acidilactici
(b)
Saccharomyces cerevisiae
(c)
P. acidilactici
+
S. cerevisiae
Lactation (10
9
cfu). Oral administration
Weaning (10
9
cfu/kg). Included in feed
E. coli
O149: F4 K88 (10
9
cfu) 21 →
49 +50 +51
Yes Before challenge: (a) increased T-cell differentiation.
After challenge: (a, b, c) Reduced bacterial
translocation. (b) Increased ileal immunoglobulins
Zhang
et al.
(2010)
Lactobacillus rhamnosus
GG (10
11
cfu/day)
Oral administration
ETEC 149: K91, K88ac (10
10
cfu) 18 →26 Yes Reduced diarrhea scores and fecal coliform shedding.
Modulated microbial diversity. Increased jejunal
immunoglobulins. Modulated systemic inflammatory
cytokines
Bhandari
et al
. (2010)
E. coli
(4.5 ×10
12
cfu)
Included in feed (daily mix)
1
E. coli
K88 (1.2 ×10
11
cfu) 21 →27 Yes Reduced ETEC in ileum. Improved animal performance
Wang
et al
. (2009)
Lactobacillus fermentum
I5007 (2 ×10
9
cfu)
Oral administration
E. coli
K88ac (2 ×10
9
cfu) 21 →21 Yes Increased T-cell differentiation and ileum cytokine
expression
Konstantinov
et al
.
(2008)
Lactobacillus sobrius
DSM 16698 (10
10
cfu)
Included in feed (daily mix)
1
ETEC K88 O149 F4 (1.5 ×10
10
cfu) 21 →28 Yes Reduced levels of ETEC in the ileum, improved
performance and increased diarrhea
Krause
et al
. (2010)
E. coli
(1.5 ×10
11
cfu)
Included in feed (daily mix)
1
E. coli
K88 (1.4 ×10
10
cfu) 17 →24 Yes Increased animal performance and microbial diversity.
Reduced diarrhea scores (in presence of raw potato
starch)
Daudelin
et al
. (2011) (a)
Pediococcus acidilactici
MA18/5 M
(b)
S. cerevisiae
SB-CNCM I-1079
(c)
P. acidilactici
+
S. cerevisiae
Sows: gestation (3 ×10
9
cfu ) +lactation
(6 ×10
9
cfu). Included in feed (daily mix)
1
Piglets: lactation (1 ×10
9
cfu). Oral
administration
Weaning: 2 ×10
9
cfu/kg. Included in feed
ETEC 0149 F4 (5 ×10
9
cfu) 21 →28 Yes (a, b) Reduced ETEC attachment to intestinal mucosa.
(a,c) Induced ileum cytokine expression
Trevisi
et al
. (2011)
L. rhamnosus
GG (6 ×10
9
cfu)
Included in feed (daily mix)
1
ETEC F4 (1.5 ×10
10
cfu) 21 →28 No Reduced animal performance. Increased diarrhea
scores. Reduced serum immunoglobulins. Tended to
a worse histomorphology
Use of probiotics in post-weaning piglets
2491

Table 1 (
Continued
)
Probiotic Pathogen Animals
References Strain, dose per pig and dosing method Strain and dose per pig
Days old: weaning
→Inoculation Benefits Main results
Li
et al
. (2012)
L. rhamnosus
ACTT 7469 –High (10
10
cfu)
and low dose (10
12
cfu)
Oral administration
ETEC F4 K88 (10
10
cfu) 21 →28 Yes High and low dose reduced fecal coliform shedding and
improved diarrhea scores (low dose was more
effective)
Guerra-Ordaz
et al
.
(2014)
Lactobacillus plantarum
JC1 B2028
(2 ×10
10
cfu)
Included in feed (daily mix)
1
ETEC K88 (1.2 ×10
10
cfu) 25 →33 Yes Improved ileal histomorphology. Reduced systemic
inflammatory cytokines. Improved fermentation
profile in ileum and colon
Zhu
et al
. (2014)
L. rhamnosus
ACTT 7469 –High (10
12
cfu)
and low (10
10
cfu) dose
Oral administration
ETEC F4 K88 (10
10
cfu) 21 →28 Yes Both doses improved diarrhea scores. Modulated ileal
T-cell differentiation. High dose increased serum
cytokine expression
Zhou
et al
. (2015)
Bacillus licheniformis
DSM 5749 +
B. subtilis
DSM 5750 –high (8 ×10
8
cfu) and low
(4 ×10
8
cfu) dose
Oral administration
ETEC 0149 F4 K88 (10
10
cfu) 21 →28 Yes Increased serum and ileal T-cell differentiation. Low
dose: increased jejunal cytokine expression
Trevisi
et al
. (2015)
S. cerevisiae
CNCM I-4407
(5 ×10
8
cfu/kg) Included in feed
(2 ×10
11
cfu/kg) Oral administration
E. coli
0149 F4ac (10
8
cfu) 24 →31 Yes Reduced diarrhea scores. Reduced fecal ETEC shedding.
Modified blood metabolic profile
Yang
et al
. (2016)
B. licheniformis
DSM 5749 +
B. subtilis
DSM
5750 –high (8 ×10
8
cfu) and low
(4 ×10
8
cfu) dose
Oral administration
ETEC/VTEC/EPEC F4+(10
10
cfu) 21 →28 Yes Increased intestinal cytokines and epithelial barrier
integrity
Zhang
et al
. (2017)
B. licheniformis
DSM 5749 +
B. subtilis
DSM
5750 –high (4 ×10
9
cfu), moderate
(8 ×10
8
cfu) and low (4 ×10
8
cfu) dose
Oral administration
ETEC 0149 F4 K88 (10
10
cfu) 21 →28 Yes Modulated microbiota and improved
histomorphological parameters
Barba-Vidal
et al.
(2017a)
B. longum
subsp.
Infantis
CECT7210
(10
9
cfu)
Oral administration
ETEC K88 (5 ×10
9
cfu and 5 ×10
10
cfu) 21 →26 +27 Yes Reduced intestinal colonization of pathogens. Stimulated
local immune response. Effects on feed intake, microbial
fermentation and intestinal architecture showed a
differential pattern between challenged and non-
challenged animals (not favorable in challenged animals)
Trevisi
et al
. (2017)
S. cerevisiae CNCM I-4407
(5 ×10
8
cfu/kg)
Included in feed
E. coli
0149 F4ac (10
8
cfu) 24 →31 Yes Improved intestinal architecture. Limited early
activation of gene sets related to impairment of
jejunal mucosa
Casey
et al
. (2007)
Lactobacillus murinus
DPC6002 and DPC6003,
Lactobacillus pentosus
DPC6004
,
Lactobacillus salivarius
DPC6005, and
Pediococcus pentosaceus
DPC6006.
Probiotic mix (4 ×10
9
cfu) or fermentate
(4 ×10
10
cfu).
Oral administration
Salmonella typhimurium
(10
8
cfu) N/A →N/A +
15 +16 +17
Yes Reduced diarrhea scores. Increased animal
performance. Reduced fecal
Salmonella
shedding
Barba-Vidal, Martín-Orúe and Castillejos
2492

Szabó
et al
. (2009)
E. faecium
NCIMB10415 (Microencapsulated).
Sows (10
9
cfu/kg), suckling piglets and
weaned piglets (2.5 to 3 ×10
8
cfu/kg)
Included in feed
S. typhimurium
DT104 (6 ×10
9
cfu) 14 →28 No Increased colonization and fecal shedding of
Salmonella
. Increased serum immunoglobulins
Walsh
et al
. (2012)
E. faecium +B. subtilis +B. licheniformis
(10
9
cfu/L for each strain)
Included in drinking water
S. typhimurium
(10
10
cfu) 19 →25 No Increased coliform shedding, no effect on
Salmonella
scores. Prevented decrease in animal performance
Kreuzer
et al
. (2012)
E. faecium
NCIMB10415 (Microencapsulated).
Sows, suckling piglets and weaned piglets
(10
9
to 5 ×10
9
cfu).
Included in feed
S. typhimurium
DT104 (2 ×10
10
cfu)
38 days
28 →38 No Reduced animal performance. No effect on fecal
Salmonella
shedding. Increased pathogen
translocation
Yin
et al.
(2014) (a)
Lactobacillus zeae
(b)
Lactobacillus casei
Fermented feed (10
9
cfu/ml)
S. typhimurium
DT104 (10
6
to 10
7
cfu)
31 days
28 →31 Yes (a, b) Improved diarrhea scores. Decreased rectal
temperature, serum haptoglobin concentrations
and fecal
Salmonella
shedding.
(a) Reduced pathogen translocation
Naqid
et al
. (2015)
L. plantarum
B2984 (10
10
cfu/day)
Included in feed (daily mix)
1
S. typhimurium
SL1344 (10
8
cfu) 28 →35 Yes Increased serum immunoglobulins
Upadhaya
et al
. (2017) a)
B. subtilis
RX7 (1 ×10
9
cfu/g)
b)
Bacillus methylotrophicus
C14
(1 ×10
9
cfu/g)
Included in feed
S. typhimurium
(10
11
cfu) 28 →39 Yes (a, b) Decreased
Salmonella
fecal shedding. Modulated
microflora, serum systemic inflammatory cytokines
and stress biomarkers
Barba-Vidal
et al
.
(2017c)
B. licheniformis
CECT 4536 (10
9
cfu/kg)
Included in feed
S. typhimurium
(5 ×10
8
cfu) 24 →31 Yes Reduced the colonization and fecal shedding of
Salmonella
. Positive effect on some behavioral
displays
Barba-Vidal
et al.
(2017a)
B. longum
subsp.
Infantis
CECT7210 (10
9
cfu)
Oral administration
S. typhimurium
(2 ×10
9
cfu and
6×10
9
cfu)
24 →32 +34 Yes Reduced pathogen shedding. Stimulated local immune
response. Effects on feed intake, microbial
fermentation and intestinal architecture showed a
differential pattern between challenged and non-
challenged animals (not favorable in challenged
animals)
Barba-Vidal
et al
.
(2017b)
B. longum
subsp
. infantis
CECT7210 and
Bifidobacterium animalis
subsp
. lactis
BPL6
(10
9
cfu)
Oral administration
S. typhimurium
(5 ×10
8
cfu) 28 →35 Yes Reduced pathogen shedding. Decreased rectal
temperature. Decrease of diarrhea scores.
Worsened voluntary feed intake, villous:crypt ratio
and fermentation profiles. Stimulation of the
intestinal immune system
Ahmed
et al
. (2014) (a)
Lactobacillus reuteri avibro
(10
10
cfu/kg)
b)
B. subtilis
+
B. licheniformis
(3.2 ×10
9
cfu/kg)
Included in feed
S. typhimurium
KCTC2515
(3 ×10
9
cfu) +
E. coli
KCTC2571
(1 ×10
9
cfu)
28 →28 Yes (a, b) Increased animal performance and nutrient
digestibility. Reduced
Salmonella
and
E. coli
shedding
N/A =not available.
1
Daily mix: probiotic suspended on a daily basis and mixed with feed.
Use of probiotics in post-weaning piglets
2493

enterocyte determined by inflammatory stress, is normally
associated with weaning (Lallès
et al
., 2004). This perme-
ability has been reported to be affected by probiotic
treatments such as in Trevisi
et al
. (2008), who reported an
increase in translocation with a
Bifidobacterium animalis
and
fructo-oligosacccharide treatment in post-weaning piglets.
Consequently, an elevated risk of sepsis could be forecast in
post-weaning animals when using probiotics (Verna and
Lucak, 2010). Moreover, it has also been reported that some
probiotics may have immune-suppressive effects in the host
(Siepert
et al
., 2014). This effect has no disadvantageous
consequence in a healthy context. Nevertheless, in the need
of a rapid humoral response, the immune activation is less
efficient (Bosi and Trevisi, 2010) and therefore would also be
deleterious in a disease situation. Thus, in a context of
increased permeability, it can been hypothesized that some
probiotics could impair the immune response and increase
risk of sepsis in some animals, despite the observed reduc-
tions in pathogen loads.
As stated before, the increase of basic research on probio-
tics is fundamental to improve the use-criteria of probiotics in
the field and to obtain reproducible outcomes. Such a tailored
use of probiotics requires a great amount of knowledge of
probiotic intrinsic capacitiesand also of how probiotics modify
ecological dynamics of the intestinal microbiota, depending on
factors like sanitary status, genetics or feeding practices,
among others. Fortunately, there has been great technological
development during the last few decades. Nowadays, we have
asufficient amount of quality trials to begin to characterize the
strains in relation to their mechanisms of action and interac-
tions with the hosts. This is interesting because it opens a door
to knowledge-based treatments, taking into account the
context in which they are applied.
How to improve the use of probiotics in early life stages
In view of the present situation, it goes without saying that
improving the use of probiotics in the swine industry relies on
a drift from an empirical use to a more knowledge-based
strategy. This section provides a few suggestions to be con-
sidered in the use of probiotics in early life stages, and in
particular in post-weaning disorders. However, its aim is solely
to provide a starting point for the reader to critically evaluate
the use of probiotics, rather than a dissertation on their use.
To start with, assessment of the probiotic strains should be
done in a wide range of health conditions. As commented by
Bosi and Trevisi (2010), the identification of strains with
positive effects in a broad range of gut health situations, and
even capable of working in different species is economically
interesting for the additive industry. However, in some cases,
although specific strains had demonstrated positive effects in
a normal physiological situation, they were reported to be
detrimental in challenge situations in piglets (see Table 1).
Hence, in our opinion, it would be highly recommended to
characterize the possible risks of using a probiotic in a
disease context, building clear differences whether probiotic
usage is intended as a therapy or as prophylaxis. For
instance, in human studies, a clear distinction is made
between research aimed at maintaining health and that
which aimed to treat a disease, and this difference has
important implications when designing trials and in
regulatory affairs (Hill
et al
., 2014).
A second issue to address is the capacity of probiotics to
modulate microbiota. As commented before, until today one
major interest when using probiotics has been to replace
antibiotics via production of
in situ
antimicrobial compounds
or enzymes to cure infections (Patil
et al
., 2015). Although
some particular strains may have demonstrated effects here
(Bhandari
et al
., 2008; Cheikhyoussef
et al
., 2008), their
usefulness in this aspect is limited and spectacular
improvements such as eliminating pathogen excretion are
rarely reported (see Table 1). However, probiotics become
much more powerful and valuable when we use them as
‘preventive’health promoters and gut microbiota stabilizers
(Simmering and Blaut, 2001). There is an increasing amount
of scientific publications supporting that probiotic effects in
gut ecology and/or immune stimulation may provide support
to keep animals healthy (Zhang
et al
., 2010; Klaenhammer
et al
., 2012; Prieto
et al
., 2014; Zacarías
et al
., 2014). In
addition, new selection criteria based on the mechanisms of
action of the strains can allow the apparition of other
probiotics that have not been previously considered in
animal production but can enhance gut health and make it
more robust. Besides, to increase control on their effects,
probiotic strategies should be more focused. Strains should
be selected depending on the objectives being looked for,
and not as if probiotics were beneficial for everything. Effects
should target specifically to a site. Targeting, for example,
M cells if applications seek to boost intestinal immunity by
enhancing development of secretory IgA (Corthésy
et al
.,
2007), or targeting the hypothalamic–pituitary–adrenal axis
if we want to improve animal well-being and reduce effects
of common stressors (Hardy
et al
., 2013; Zhou and Foster,
2015). In addition, some specific probiotic strains adapted to
the colonic environment could be good candidates to fight
gut dysbiosis (Corthésy
et al
., 2007), but other strains could
be better to enhance productive performance based on
their enzymatic hydrolysis properties (Kim
et al
., 2007) or
biosynthetic pathways for amino acids’new synthesis
(Pridmore
et al
., 2004). Hence, further assessment and clas-
sification of commercial probiotics in relation to their
mechanisms of action are desirable, to be able to implement
strategies that are more precise and oriented to specific
needs of these animals.
Another point to take into account is the variability in the
response to a probiotic, depending on the host or the herd in
which it is introduced. It has been described how a probiotic
strategy may have ‘responder’and ‘non-responder’indivi-
duals in a homogenous group of animals, and also how
different microbial environments can determine variability
among herds (Klaenhammer
et al
., 2012; Arora
et al
., 2013;
Starke
et al
., 2013). For instance, it has been described how
the genetically determined different presence of sugar com-
plexes along the host gut surface may facilitate the adhesion
Barba-Vidal, Martín-Orúe and Castillejos
2494

on the glycocalix of some enteropathogens, possessing
specific colonization factors (such as
E. coli
F18 and K88)
and, possibly, of commensal bacteria (Krogfelt, 1991; Lee
et al
., 2013). Moreover, the emerging ‘-omic’technologies
clearly open a window to refine our approach and under-
stand better the interactions between a probiotic strain and
the ecosystem in which it is going to be introduced. It is
expected that by increasing our understanding in pig micro-
biome knowledge, we will identify key microbial groups of
the piglets gut with an important role in maintaining a
productive and disease-resistant ecosystems (Kim and
Isaacson, 2015). In addition, we will eventually be able to
identify the most appropriate strain (or strains) to use as
specific probiotic treatments for a particular situation
depending on the targeted microbial ecosystem (Sanders
et al
., 2013). For instance, two enterotype-like clusters have
recently been identified in pig microbiota significantly
correlated with performance (Ramayo-Caldas
et al
., 2016).
Likewise, to correlate probiotic effects to specific enterotypes
would reasonably reduce the variability of empirical use. On
the other side, our understanding in probiotic interactions
with the host and in particular with the intestinal cells gene
expression has greatly improved in recent years. For example,
a common mechanism for the anti-inflammatory activity of
several probiotics has been described to be regulated by the
micro-organisms pattern recognition receptors
toll-like receptor
2(TLR-2)
(Villena
et al
., 2012; Tomosada
et al
., 2013). In
addition, it has been described how selective pressures among
European pig populations have derived into specific
TLR-2
gene
variants (Darfour-Oduro
et al
., 2016). Overall, this is interesting
because it provides a common mechanism for the anti-
inflammatory activity of several probiotics (including different
strains such as
Lactobacillus
spp. and
Bifidobacterium
spp.)
(Tomosada
et al
., 2013). Moreover, it provides a potential
biomarker for the screening and selection of new immune-
regulatory strains, to be used efficiently at a population level to
enhance immunity.
Furthermore, another possibility to potentiate probiotic
effects would be to combine probiotics with complementary
actions, with many beneficial examples reported in the
bibliography (Casey
et al
., 2007; Lessard
et al
., 2009; Zhou
et al
., 2015; Barba-Vidal
et al
., 2017b). Probiotic combina-
tions can be multi-strain probiotics, containing more than
one strain of the same species or closely related species
(for instance,
Lactobacillus acidophilus
and
L. casei
), or
multispecies probiotics, containing strains of different
probiotic species that belong to one or more genera (e.g.
L. acidophilus, Bifidobacterium longum
and
Enterococcus
faecium
) (Timmerman
et al
., 2004). It has been suggested
that the greater variety of probiotic genera present within a
mixture may reduce its effectiveness, through mutual
inhibition by the different species, antimicrobial compounds
or competition for either nutrients or binding sites (Chapman
et al
., 2011 and 2012). However, multispecies probiotics
have also been related to a broader spectrum of activity (e.g.
inhibition of a wider variety of pathogenic bacteria), and if
well-designed, a greater amount of synergism and symbiosis
when different probiotic effects are combined (Timmerman
et al
., 2004). Hence, although bacterial combinations have a
high potential, beneficial properties of different strains are
not always additive (Chapman
et al
., 2011). This is not an
easy field of research and bacterial interactions inside the pig
gut ecosystem should be further explored to be able to
construct effective strategies. Still, unfortunately
in vivo
studies comparing single strains to probiotic combinations
are still rare. Additional approaches to strengthen effects
could be the addition of specific prebiotic substrates
(symbiotic concept) to selectively improve the growth
of the introduced strain (Shenderov, 2011; Arboleya
et al
.,
2016) or to promote a microbiota more favorable for the
probiotic to exert its action (Guerra-Ordaz
et al
., 2014).
Another option to improve and to specifically select
the effects of a probiotic would be the genetic manipulation
of the strain (Bjerre
et al
., 2016; Xu
et al
., 2016). However,
introduction of GMO in the animal feed is nowadays a very
controversial issue.
The way a probiotic is administered to the piglets can also
be a critical point to consider as, sometimes, reduced stability
and viability of the probiotic cells can limit the use of the
potentially most beneficial strains. Some bacterial genera are
particularly sensitive to be introduced in the dry feed, as they
cannot stand chemical–physical conditions of the feed or the
manufacturing process (Angelis
et al
., 2006). In this sense,
the development of acclimatization procedures or protective
coating to enable them to stand environmental aggression
(Sewell, 2016) is a promising field of development for the use
or probiotics as in-feed additives. Still, dry feed is not the only
way a probiotic can be administered to piglets. Daily
administration of fresh probiotic as a solid or liquid suspen-
sion by mixing it with the feed (top dressing) is a common
procedure in research trials (see Table 1). However, although
it may be a good strategy to increase the viability of
probiotics when delivered, it is a highly time-consuming
routine difficult to be implemented in commercial pig farms.
Alternatively, fermented milk, suspension in milk or even
suspension in water can be considered. For instance,
Gebert
et al
. (2011) supplemented a milk replacer with a
Lactobacillus
probiotic strain and saw positive effects on
pre-weaning animals.
Besides, early dosing of probiotics in the pre-weaning
period should be considered. Gut microbiota plays a critical
role in the adaptation from a neonatal-immature gut to a
functional adult system, resistant to adverse ecological shifts
at challenges such as weaning (Lewis
et al
. 2012). Hence,
providing probiotics at this point could potentially permit the
establishment of early and life-long health benefits (Kenny
et al
., 2011). Sows should be given more importance here, as
many studies have shown how introducing probiotics in the sow
diet is an effective way to modify the gut ecosystem and the
health of piglets (Alexopoulos
et al
., 2004; Bohmer
et al
., 2006;
Apic
et al
., 2014; Siepert
et al
., 2014; Kritas
et al
., 2015;
Scharek-Tedin
et al
., 2015). Alternatively, the introduction of
probiotic strategies via ‘creep feed’is increasingly being studied
(Alexopoulos
et al
., 2004; Shim
et al
., 2005; Giang
et al
., 2010).
Use of probiotics in post-weaning piglets
2495

Nevertheless, results of these experiments are largely variable,
probably due to the fact that piglets usually ingest small or null
quantities of them (Pajor
et al
., 1991).
Conclusions
A systematic approach should be undertaken when
designing a probiotic intervention to identify potential risk
factors of the target animals, the suitability of a specific
probiotic strain and the appropriateness of the dosing
method. This process is difficult in pig production where a
collectivity is being treated. More research is needed to
further characterize the mechanisms of action of probiotics
and their interaction in different gut health situations. We
are, nowadays, able to make science-based prescriptions of
probiotics in a limited amount of situations. However,
eventually, when sufficient evidence is built up, we will be
able to make reliable recommendations for every particular
situation. Once at this point, probiotics will be used much
more efficiently and the swine industry will be able to obtain
the most by investing in these products.
Acknowledgments
The authors would like to thank Mr Chuck Simmons, native
English-speaking University Instructor, for his correction of this
article’s language and style.
Declaration of interest
Authors declare no conflict of interest.
Ethics statement
None.
Software and data repository resources
None.
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