14 Apr Prebiotics as an alternative to antibiotics in poultry
Since their discovery over seventy years ago, antibiotics
have been our leading weapons in the treatment of
bacterial infections, including life threatening infections
in hospitals. Often, they are routinely prescribed and
taken, sometimes inappropriately. Antibiotics are also
used in the food animal production for therapy, disease
prevention and growth promotion.
However, their transforming powers are under threat
because their indiscriminate use has triggered antibiotic
resistance, and in many cases, they no longer work.
Antibiotic resistance is an expected and natural
mechanism and refers to a situation where an antibiotic
that normally would stop growth of a certain type of
bacteria no longer does that.
Use and misuse of antibiotics in both humans and
animals can make bacteria resistant. Furthermore, resistance can be transmitted between
humans, between animals, and between humans, animals and the environment. Transmission
and spread of bacteria or genes that carry the resistance information can occur in hospitals, in
the community, and through the food chain. Antibiotics have also been found in the
environment, for example in some water supplies.
Infections from resistant bacteria can be difficult and sometimes impossible to cure, and they are
increasing. Meanwhile, research into the development of new antibiotics that will work is very
costly and lengthy, and resistance often develops rapidly after new antibiotics are marketed.
Currently, very few new antibiotics are in the development pipeline. Without new and effective
antibiotics, but with increasing resistance, society could return to the conditions of a preantibiotic
era, when a simple lung infection could kill a child, or when doctors could not fight
meningitis. A number of advanced medical interventions and diagnostics would also be
impossible because of the lack of effective antibiotics for prophylaxis.
The use of antibiotics in the poultry sector is mainly for treatment, prophylaxis and growth
promotion. In many parts of the world, food-producing animals are given antibiotics daily to
make them grow faster and prevent diseases. This trend is likely to continue given the growing
demand for the protein of animal origin. When antibiotics are used for the purposes of growth
promotion a small amount is often administered as compared to therapeutic use. Therefore, this
may cause bacteria to develop resistance to antibiotics. The emergence and spread of antibiotic
resistance compromise the nutritional and economic potential of poultry and other food producing
This is a global concern that affects both animal and human ecosystems. According to the report
Antibiotics 2020, 9, 594; doi:10.3390/antibiotics9090594 www.mdpi.com/journal/antibiotics
Antibiotics 2020, 9, 594 2 of 18 commissioned by the United Kingdom (UK), it is estimated that
almost 10 million people could die of bacteria that are resistant to the antibiotic by 2050. In the
United States, over 2 million people get infected by antibiotic-resistance bacteria and around
23,000 of them die due to the resistance to treatment. The World Health Organization (WHO)
has published a report regarding the incidence of antibiotic-resistance which shows an increase
in the Asian continent. In the US and Europe alone, antimicrobial-resistant cause overs 50,000
deaths annually. Antimicrobial resistance threatens food security, animal welfare, longer
treatment cycle and public health worldwide. There are many factors that contribute to the
irrational use of antibiotic: Attitudes, perception of policymaker’s knowledge, manufacturer,
prescribers, consumers and dispensers. The European Union (EU) banned antibiotic use in animal
production in 2006. A retrospective study analyzing the relationship between prior
antibiotic use with antimicrobial-resistant was conducted in Indonesia and the results showed
that patients who have a history of antibiotic use over the previous three months had shown an
escalation of the probability of higher resistance matched to the patient’s history of antibiotic
use over the preceding months.
In 2018, WHO declared the week of 18–24 November to be an annual antibiotic awareness
campaign week with the aim of increased responsiveness of global antibiotic resistance hazard.
The cause of resistance to antibiotics is a topic that is receiving much attention, factors such as
inappropriate use of antibiotics, bacterial gene mutations and horizontal gene transfer between
bacterial species are amongst the key contributing factors. Gram-negative bacteria such as
Acinetobacter spp., Escherichia coli, Klebsiella spp. and Salmonella spp. are some of the
microorganisms that are extremely resistant to existing antibiotics. Escherichia coli, Salmonella
spp., and Campylobacter spp. are some of the main bacteria that cause diseases in poultry.
According to the WHO antibiotics such as fluoroquinolones used in agricultural animals have
resulted in the development of ciprofloxacin-resistant Salmonella, Campylobacter and E.coli.
which contributed to human infections that were difficult to treat. Apart from developing
antibiotic resistance, the public can also develop an allergic reaction or liver damage on the
resistance of consuming antibiotic residues in animal products. Campylobacter spp. are prevalent
in South African poultry products and pose a threat to human health. It can affect the
gastrointestinal tract and causes diarrheal illnesses.
Antibiotics that are important for treating humans must be prohibited from being used in the
feed as growth-promoting. There are many international programs and platforms that have been
developed to address the antimicrobial resistance issue. Programs such as antibiotic stewardship,
therapeutic drug committee can be used as a standard measure for collecting and comparing
drug utilization patterns within and between countries. International organizations at the
forefront of addressing antimicrobial resistance such as FAO, WHO, and OIE (World Organization
for Animal Health) have invested enormously on advocacy on public health risk associated with
the use of antibiotics. Studies examining antimicrobial use and antibiotic resistance is widely
Consequences of Removing Antibiotics from the Poultry Feed
The use of antibiotics is known to improve chicken health and result in weight gain. Although it
comes with a cost, none the less their removal will have consequences in animal production.
Cowieson and Kluenter, believe that the addition of antibiotics in animal generates substantial
increases in feed conversion ratio and weight gain up to 4%. This improvement must be forgone
on banning the use of antibiotics or even negative growth in poor-performing flocks. Moreover,
the removal of antibiotic growth promoters (AGPs) could increase necrotic enteritis due to
reduction in Clostridium perfringens control making pathogens attack more likely. A study by
Cardinal et al. found that the withdrawal of antibiotics growth promoters from the diet of broilers
increased the cost of production, which will eventually increase the price tag for poultry meat.
On the other hand, the negative effect due to the removal of prophylactic drugs may only show
on the broiler performance after the first year without the use. The promotion of alternative
substances to antibiotics in poultry should be at the center of antimicrobials campaign.
Alternatives such as prebiotic and probiotic will be discussed in detail below.
The Environmental Impact of Antibiotics
The emergence of antibiotic-resistant bacteria in the environment is a global threat to the public.
The rapid spread of multiple antibiotic resistance microbes in the environment is the main
concern considering the low investment in developing new antibiotics. The wastewater
treatment plants are regarded as a threat to public health simply because the three-stage
treatment process is insufficient to remove all the pharmaceutical residues. The wastewater
treatment plants serve as carriers and transmitters of the antibiotic-resistance border between
humans and the environment. Wastewater from hospitals, households and poultry farms waste
contains antibiotic-resistance bacterial of animal and human origin. A study conducted in the
Eastern Cape province of South Africa revealed that wastewater treatment plants could be one
of the contributors of sources of antibiotic-resistant Escherichia coli. The wastewater treatment
plants in West Africa are also regarded as the major sources of antibiotic-resistant bacteria.
Bougnon and colleagues also reported that in Burkina Faso water from sewages used for urban
agriculture may likely be one of the major sources spreading pathogens and antibacterial
resistance among animals and humans.
Most rivers are considered sources of antibiotic pollution. Residues from farms and human
environment may contain antibiotic-resistant genes and antibiotic substance that can
contaminate the environment. The emergence of antibiotic-resistant genes in the water
environment is becoming a global concern. Mhlathuze River in South Africa has enteric bacteria
that are resistant to antibiotic except gentamicin, the Lactamase gene may be widely distributed
in the environment.
Similar findings were also reported in the Eastern Cape province of South Africa that multiple
antibiotic-resistant Pseudomonas species were prevalent in chlorinated municipal wastewater.
The presence of antibiotics residues in the environment is not only the African problem. Karst
river in China is widely contaminated with the presence of antibiotics. The presence of antibiotics
in rivers pose a high ecological risk to the most vulnerable aquatic organisms. An integrated
approach could be a solution to combat antimicrobial resistance. Pseudomonas aeruginosa that
was isolated from the environmental and clinical origin in the Benin City of Nigeria was 100%
resistant to cefuroxime and amoxicillin.
The presence of enteric bacterial and their resistance to the antibiotic in the environment at
Kakamega town in Kenya is a challenge that can cause a health hazard to the public. In Kenya
the highest concentration of antibiotics was found in the suburban soil of Narok town (west of
Nairobi), antibiotic such as Oxytetracycline, Sulfamethoxazole, enrofloxacin and sulfamethazine
were identified as the main antibiotics contaminated in soils. Therefore, it is imperative that
sustainable microbial monitoring program developed by the Africa CDC and WHO be implement
The information regarding the presence of antibiotic-resistant pathogens in the environment is
limited in Africa. The occurrence of antibiotic-resistant bacteria in the environment is a hazard to
global Antibiotics 2020, 9, 594 8 of 18 public health. Therefore, detailed studies with monitoring
and surveillance programs could serve as a good starting point in understanding antibiotic
resistance in the African environment and developing mitigation strategies thereof.
Market-based decision to replace antibiotic growth promoters
The unrelenting demand by many activist groups, calling for total cessation of the use of
antibiotic growth promoters in poultry production, is not always supported by scientific
justification. Nevertheless, major poultry companies (Tyson Foods, Perdue Farms, and Foster
Farms) that produce one third of the chicken consumed in the United States have stated that
they have voluntarily taken most if not all of the antibiotics out of the feed provided for healthy
chickens. Part of the recent response by the poultry companies was due to the potential that
ciprofloxacin, used to treat anthrax in humans, might contribute to antibiotic resistance in
anthrax. Additionally, the poultry companies are reacting to edicts from some corporate
consumers (McDonald’s, Wendy’s, Kentucky Fried Chicken, and Popeye’s) that are refusing to buy
poultry that had been treated with ciprofloxacin and now all other antibiotic growth promoters.
These market-based policy developments in corporate America signaled a change of attitude in
the corporate world of poultry production.
Time for probiotic usage in poultry production
The ban of growth promoting antibiotic usage in the EU will ultimately affect every poultry
exporting country because poultry products found to have antibiotic residues of EU-banned
products or to harbor bacteria such as S. typhimurium DT104, Staphylococcus aureus,
Acinetobacter, Listeria moncytogenes, Enterococcus faecalis, pathogenic Escherichia
coli, or Camplyobacter jejuni, that have multiple antibiotic resistance profiles, likely will be
refused. Provision of a healthy food supply is the primary goal of the global poultry industry, and
in order for the global industry to remain viable in the 21st century, it must be able to make
changes to meet the demands of the consumers of its products. When consumers of a product
develop an idea or perception about a product, no matter that there is no scientific data to
support or refute the perception, that perception becomes real for that consumer. If large
numbers of consumers accept those perceptions, then pressures are placed upon the producer
to make the product conform to the standards set by the consumer. Thus, alternatives to subtherapeutic
antibiotic growth promoters must be developed. Therefore, this review will address
the concept of probiotics for use in the poultry industry as an alternative to antibiotic growth
Production and secretion of antimicrobial metabolites
Many of the probiotic organisms that produce antimicrobial substances often times will have an
advantage over organisms that grow and compete vigorously for intestinal sites for colonization.
Antimicrobial substances produced and secreted by natural inhabitants of the intestinal tract can
either kill or inhibit growth of pathogens (Rolfe, 1991). Generally, most bacteria produce agents
that either kill or inhibit related species or even different strains of the same species of bacteria
(Iglewski & Gerhardt, 1978). These products include the short chain volatile fatty (lactic,
propionic, butyric, and acetic acids), hydrogen peroxide, and diacetyl and each has a different
mode of action.
Additionally, there are metabolic products frequently classified as bacteriocins to distinguish
them from antibiotics. Bacteriocins are produced by a large variety of organisms and the
bacteriocins are frequently mediated through plasmids (Mishra & Lambert, 1996). Bacteriocins
are proteinaceous compounds of bacterial origin that are lethal to bacteria other than the
producing strain. It is assumed that some of the bacteria in the intestinal tract produce
bacteriocins as a means to achieve a competitive advantage, and bacteriocin-producing bacteria
might be a desirable part of competitive exclusion preparations (Joerger, 2003). In this capacity,
the acid-loving Lactobacilli have shown that as a group, they produce significant amounts of
bacterial growth inhibitory substances such as nisin and reuterin. Nisin is generally recognized as
safe. Its mode of action is as a targeted membrane-permeabilizing peptide that induces pore
formation in bacteria (Breukink et al., 2003). Reuterin, a product of glycerol metabolism that is
secreted by L. reuteri, has broad-spectrum killing abilities in the intestinal tract of chickens
(Dobrogosz et al., 1989; Talarico et al., 1988, 1990; Talarico & Dobrogosz, 1989, 1990). Bacillus
subtilis now used as an oral probiotic organism has a wide range of antimicrobial activities
associated with a serine protease called subtilisin. It has been demonstrated that Bacillis
subtilis facilitates the growth of another probiotic organism, L. reuteri, through production of
catalase and subtilisin (Hosoi et al., 2001). Colicin is produced by E. coli to enhance their
competitiveness in the gut of animals. Colicins are plasmid-encoded polypeptide toxins produced
by and active against E. coli and closely related bacteria. The channel-forming colicins are
transmembrane proteins that depolarize the cytoplasmic membrane, leading to dissipation of
cellular energy (Parker et al., 1992; Braun et al., 1994).
Performance of poultry given probiotics
Body weight gain, feed conversion and reduced mortality are characteristics of performance that
ultimately dictate whether managerial and company practices will be altered for acceptance of a
new way of managing poultry. Mead (2000) described field experiences with competitive
exclusion usage for control of Salmonella in poultry and clearly states that it is possible to control
pathogen infection without sub-therapeutic antibiotic application, which was incompatible with
probiotics. In field trials with market turkeys, we have demonstrated that Lactobacillus
reuteri improved weight gain at 120 days of age by 4.8% (Casas et al., 1998). In ovo Lactobacillus
reuteri-treated broiler chickens given a S. typhymurium challenge, body weights were improved
by 206 g at 40 days of age and mortality was reduced by 32% (Edens et al., 1997a). Lan et al.
(2003) reported that broiler chickens given Lactobacillus agilis JCM 1048 and Lactobacillus
salavarius subsp. salicinius JCM 1230 significantly increased weight gain by 10.7%. Use of Bacillus
subtilis (Calsporin; Calpis Corporation, Tokyo, Japan) did not improve body weight (Calsporin
2416 g vs. control 2407 g) at 42 days of age but feed conversion was improved (Calsporin 1.741
vs. control 1.773) (Edens, unpublished), but Fritts et al. (2000) have shown that Calsporin will
improve broiler body weight gain and fed conversion. There is only one report on a probiotic
product based upon the presence of Bacillus subtilis in Calsporin, that demonstrates the
effectiveness of Bacillus subtilis in significantly reducing carcass contamination from enteric
bacteria that have the potential to become human pathogens (Fritts et al., 2000). However, there
are earlier reports indicating that Bacillus subtilis can effectively reduce the numbers of potential
pathogens in feces from broiler chickens (Maruta et al., 1996a) and from swine (Maruta et al.,
Laying hens have needs that differ from broilers. Among the problems the laying hen encounters
is S. enteritidis that contaminates eggs. As indicated already, it is possible to use probiotic
bacteria to reduce or eliminate the S. enteritidis problem. However, there are other benefits to
the egg producer. Pedroso et al. (1999) have reported that the use of probiotics (Bacillus subtilis)
improved feed conversion and eggshell thickness. Improvement of these two factors alone will
result in significantly improved profit margins for the egg producer.
Use of probiotics as a routine practice in meat and egg producing poultry species has had a slow
start, but it appears that increasing pressures from consumers will force the industry to adapt or
fail. Adaptation simply means that antibiotics are no longer acceptable by the consumer of
poultry products. If there is a small increase in the cost of production due to some alternative to
antibiotic growth promoters, the consumer appears to be prepared to pay the additional cost.
Market driven decisions by corporate consumers of poultry products, in response to pressures
from is customers, will also drive the poultry industry to adapt to a new standard of probiotics.
Thus, the company that adapts will survive in the near future, but the company that does not
adapt will fail and ultimately will cease to exist. Therefore, the benefit, that the commercial
poultry industry will be derived from the change from antibiotic growth promoters to probiotics,
will be survival. Survival is then measured in terms of maintenance of market shares and
continued domestic and international sales. However, the industry will also derive the benefit of
improved welfare status of their flocks. It is not uncommon to find that improved welfare also is
associated with improved performance and improved profit margins. In time, it appears that
antibiotic resistance factors might be lost from potentially zoonotic bacteria, and this would
result in less difficulty in maintenance of flock health and public health of the consumers of
poultry products. Therefore, the commercial poultry industry has numerous benefits to be gained
from the use of probiotics and much to lose if it does not adapt to the new era where consumers
tell producers how to produce the product that will be purchased.
Future for probiotic application
Public concerns about food animal production and food safety will drive decision-making
processes in the future. As illustrated in this review, the public will demand specific standards in
the food production system, and if companies desire to remain in business, those companies will
respond positively to consumer demands. Thus, the future for probiotics appears to be very
strong for the poultry industry. Already, there have been many demonstrations of beneficial
effects of probiotic use in decreasing many different bacterial pathogens in live poultry and on
carcasses of processed poultry. Products that cause the reduction of human pathogens on
poultry meat will be demanded to a greater extent in the future. This is especially true with regard
to the export of products to the European Union. However, that is only the beginning. It is
anticipated that other major import markets will also demand antibiotic growth promoter-free
products. In response to those demands, poultry production centers such as those in the United
States, Brazil, Thailand, and in China will respond with production of more products with reduced
microbiological risks for humans.
Increasing knowledge of bacterial resistance to antibiotics used by both humans and livestock
has contributed to development of perceptions in consumers that an alternative to antibiotics
must be identified. An understanding of the importance of the intestinal microflora in the
maintenance of health and the prevention of disease in poultry has led those consumers to
demand that in lieu of antibiotics, poultry producers should utilize probiotics or prebiotics that
stimulate the growth of probiotic bacteria in the intestinal tract of meat animals and layers.
Because perceptions are real in the mind of the consumer, it is important that the poultry
industry respond to the demands of their consumers and provide them with the types of products
they desire. Probiotics provide the dietary means to balance the intestinal bacteria in poultry and
promote a responsive and improved immune system that can detect and eliminate certain
potential pathogens from the intestinal tract. Probiotics also stabilize the intestinal mucosa
making it more difficult for pathogens to colonize and cause damage in the intestinal tract, and
they also promote a condition in which less contamination occurs on processed meat and meat
products thereby decreasing the risk of compromised human health status. With the ultimate
end of prophylactic and antibiotic growth promoter usage in the European Union and less
antibiotic usage in other poultry producing centers in the world, the future for application of
probiotics appears to be growing.
Even though a great amount of research is still required to understand the mode(s) of action of
many defined and undefined probiotic cultures and commercial products, evidence is mounting
up in strong support of the benefits that can be derived from the use of probiotics. Probiotic
products are not to be considered as antibiotics. Instant responses to the use of probiotics can
never be seen, but the use of probiotics seems to improve the longer the product is utilized in
broiler growing and egg laying facilities. Additionally, every probiotic product is different and
efficacy against specific organisms is not always the same. Thus, the producer must be able to
very specifically identify the production problem for which specific probiotics must be applied. A
single product may not solve the problem, but products used in combination may be more
The poultry industry is entering into uncharted areas now that antibiotics are being banned.
Antibiotic replacement with probiotics will create some challenges for the commercial producer,
but the rapid pace of research today often times can address those problems in short order. The
ultimate outcome of this consumer driven change to probiotics may actually become
advantageous to the producer in times to come.
However, an integrated, rational approach to the development and application of probiotics in
the poultry industry remains an issue of high priority. It is understood that all probiotics do not
act the same in the intestinal tract of poultry, and due to this diversity of action among the many
commercial products and those still in development, there is a need to characterize each
probiotic according to its influence on the physiological status of the intestinal tract. Even though
significant work has already been reported in this area, our understanding of the symbiotic
relationship between the host and the intestinal microorganisms still is very limited. Thus,
systematic investigations are required to better understand the host’s response to the probiotic
and the response of the probiotic to the micro-ecology of the intestinal tract of the host.