Non antibiotic growth promoters for livestock and poultry production

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Non antibiotic growth promoters for livestock and poultry production

R.P. Kolhe1*, V.S. Waskar2, V.D. Aher3

KNP College of Veterinary Science, Shirwal, Satara,

Maharashtra Animal & Fishery Sciences University, Nagpur, Maharashtra, 412801

 

ABSTRACT

Since its discovery, antibiotics are enormously used in human and veterinary medicine. Antimicrobials are broadly used in the treatment of ailing human and animals, however they are also used as growth promoters and enhancers in livestock and poultry. Unfortunately, antibiotics were not handled properly and its indiscriminate use in human and animals causes an emergence of antibiotic resistance. Use of antibiotics as growth promoters is now restricted by some of the countries and more emphasis is being given on non-antibiotic alternatives as feed enhancer and growth promoters. Use of prebiotics and probiotics is well established in the animal health industry. In recent years, use of phytogenic means plant based compounds is being explored by the researchers across the world. Plant based alternatives to antibiotics are known as phytobiotics and these are natural additives which help in immunomodulation’s, feed conversion and growth enhancement. Plant derived additives and other non-antibiotic supplements have multiple health benefits to livestock, swine and poultry without leaving residual effect in foods of animal origin.

Keywords: Antimicrobial resistance, antibiotics, growth promoter, non-antibiotic alternatives

 

1*Corresponding author : Assistant Professor, Department of Veterinary Public Health & Epidemiology, email-dr_kolherahul@rediffmail.com.

2Professor, Department of Veterinary Public Health & Epidemiology.

3Associate Dean, KNP College of Veterinary Science, Shirwal Dist- Satara, Maharashtra

 

Introduction:

In 2015, United Nations adopted the Sustainable Development Goals (SDGs), as a universal call to action to end poverty, protect the planet, and ensure that by 2030 all people enjoy peace and prosperity. There are total 17 SDGs which are integrated and they recognize that action in one area will affect outcomes in others, and that development must balance social, economic and environmental sustainability. Zero hunger is one of the key SDGs, however it is challenging to accomplish the food demand of growing global population. Global increase in human population is being recorded and it is expected that by 2050 it will reach to 11 billion. Glowing global population will definitely increase pressure on the world food basket. Role of animal proteins in human health and nutrition is pivotal and there is increasing demand for animal origin proteins. Livestock and poultry are the potential sectors for achieving food security in terms of their valuable contributions to agricultural sustainability and the high nutritional value of animal products in the diet. Discovery of antibiotic is one of the greatest inventions for the survival of mankind, however antimicrobial resistance (AMR) is now considered as public health emergency of international concern. Development of AMR in the bacterial population and its further spread through various modes including foods of animal origin is a matter of great concern.

Antibiotics have been used in livestock and poultry industry as growth promoter (AGP) since long. Antibiotics are supplemented in animal feed at sub-therapeutic doses to improve growth and feed conversion efficiency and to prevent infections in livestock and poultry.  In recent years some of the countries have banned use of antibiotics as AGP. Several non-antibiotic alternatives like prebiotics, probiotic-direct fed microbes, organic acids, essential oils, bacteriocin, bacteriophages, antimicrobial peptides and phytogenic plant derived compounds are being used as feed supplement, immunomodulators and growth enhancer in livestock and poultry industry. There is rise in the consumer demand for poultry products from “Raised without Antibiotics” or “No Antibiotics Ever” flocks. There has been a significant increase in scientific papers in the recent literature on antibiotic alternatives and feed additives to promote growth and enhance gut health, and reduce the use of antibiotics in animal production. Long-term use of antibiotics has led to the development of drug-resistant microorganisms, posing a threat to consumers’ and animals’ health and also exerting a negative effect on the environment.  As a result, the use of antibiotic-based growth stimulators was banned in the European Union since 1 2006. This overview focused on utilization of non-antibiotic growth promoters in livestock and poultry feed in order to curtail the incidence of AMR.

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Classification of non-antibiotic growth enhancers:

Non antibiotic growth enhancers are alternative to the antibiotics which is comprised of prebiotics, probiotics, phytobiotics, microbial metabolites, antimicrobial peptides etc. (Table 1).

Table 1. Examples of non-antibiotic growth promoters and immune-enhancers

Sr. No. Compound Examples Mechanism of action
1 Prebiotics Mannanoligosaccharides (MOS), Galactooligosaccharides (GOS), and Fructooligosaccharides (FOS) including inulin Exact mechanism is unknown, however they are fermentable feed additives that can directly or indirectly support a healthy intestinal microbiota. It enhance short chain fatty acid (SCFA) production which is considered a potential source for pathogen reduction.
2 Probiotics LactobacillusBifidobacteriumSaccharomycesEnterococcusStreptococcusPediococcus, LeuconostocBacillusEscherichia coli Nissle 1917 Probiotic administration increases the production of SCFAs. Probiotics are capable of suppressing intestinal inflammation via the downregulation of TLR expression, secretion of metabolites that may inhibit TNF-α from entering blood mononuclear cells, and inhibition of NF-κB signaling in enterocytes
3 Phytobiotics Phytogenics present in fruits, vegetables, whole grains, legumes, nuts, herbs, and essential oils Numerous studies have reported the growth-promoting effects of phytobiotics, whereas the precise mechanisms underlying the role of phytobiotics as animal growth promoters have not yet been completely elucidated.
4 Antimicrobial peptides Gramicidin, Magainin, protegrin, indolicin, and indolicin, bacteriocins In general, enzymatic mechanisms are not involved in the antimicrobial activities of AMPs. Antibacterial AMPs are the most studied AMPs to date and most of them are cationic AMPs, which target bacterial cell membranes and cause disintegration of the lipid bilayer structure. Antiviral AMPs neutralize viruses by integrating in either the viral envelope or the host cell membrane. Antifungal peptides can kill fungi by targeting either the cell wall or intracellular components.

Prebiotics:  Use of prebiotics for enriching the beneficial gut microbes is extensive in poultry and swine production. As per the definition is given in the 6th Meeting of the International Scientific Association of Probiotics and Prebiotics (ISAPP) in 2008, dietary prebiotics are defined as “a selectively fermented ingredient that results in specific changes in the composition and/or activity of the gastrointestinal microbiota, thus conferring benefit(s) upon host health”. Prebiotics are non-digestible food ingredient that beneficially affects the host. In 2016, ISAPP modified the same and the group of prebiotics may involve other substances besides carbohydrates and may act not only in the alimentary tract and they can be used in human food, and animal nutrition. Prebiotics play important role in livestock and poultry nutrition. These are non-digestible carbohydrates utilized by the beneficial microbiota present in the gut. Most common prebiotic compounds are fructo-oligosaccharides (FOS), galacto-oligosaccharides (GOS), and trans-galacto-oligosaccharides (TOS).  Microbial fermentation of prebiotics yields short-chain fatty acids (SCFAs), including lactic acid, butyric acid, and propionic acid eliciting multiple effects on the host.

 

Probiotics:  This term is derived from a Greek word “bios” meaning “of life”. It is use of living non-pathogenic organisms for deriving beneficial effects on the host. According to the FDA and WHO probiotics are “Live microorganisms which when administered in adequate amounts confer a health benefit to the host”. Bacteria, bacteriophages, microalgae, and yeasts are all examples of probiotics. Most commonly used beneficial microbes as a probiotic are Lactobacillus rhamnosusLactobacillus reuteri, Bifidobacterium, Lactobacillus caseiLactobacillus acidophilus-group, Bacillus coagulans, Escherichia coli strain Nissle 1917, Enterococcus faecium SF68, Saccharomyces boulardii etc. For characterization of any strain as a potential probiotic, the FAO/WHO guidelines on probiotics must be used as global standard. Probiotic strains must be able to survive and propagate in the digestive tracts of host, must withstand acidic pH,  must be non-pathogenic and no toxic, free from undesirable side effects, stable, suitable for large-scale production and must exhibit beneficial health effects.  It has gained popularity in the livestock and poultry industry due to consumers demand for antibiotic free animal origin foods.  In recent years, multi-strain probiotics are being prepared for ruminants, poultry and swine.  Three important pathways through which probiotic show beneficial effect are; competitive exclusion, bacterial antagonism, and immune system stimulation. Appropriate concentration of probiotic strain is crucial and for most of the probiotic strains, recommended dose is 109 CFU/kg of feed.

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Synbiotics: It is use of combination of prebiotic and probiotic for high degree of effectiveness of in animal nutrition.  Synbiotic refer to the products in which the prebiotic compound selectively favour the probiotic organism. Synbiotics were developed to overcome possible survival difficulties for probiotics. The probiotic strains used in synbiotic formulations include Lacbobacilli, BifidobacteriaS. boulardiiB. coagulans etc., and foremost prebiotics used FOS, GOS, xyloseoligosaccharide (XOS) and inulin.  Synbiotics are alternative feed additives for livestock and poultry.

 

Phytobiotics:  Herbal or plant based compounds have several beneficial advantages and they are considered as potential alternative to the antibiotic growth promoters especially in monogastric animal species. It is a broad subset of plant-derived bioactive compounds. They are commonly known as phytobiotics, phytogenics, or phytogenic feed additives (PFA) meaning a wide range of bioactive plant-derived compounds that are incorporated into animal diets as herbs, spices, extracts, or essential oils.  Phytobiotics are secondary plant metabolites and acts as antioxidants, digestive enhancers, nutraceuticals, and health promoter. They can also modify the gut microflora positively by reducing the number of pathogenic organisms. Over five thousand dietary phytobiotics have been identified in fruits, vegetables, grains, legumes, nuts, herbs, and essential oils. They are broadly classified as: phenolic compounds, alkaloids, nitrogen-containing compounds, organosulfur compounds, phytosterols, and carotenoids. Four principal mechanisms by which phytobiotics may induce growth promotion are: i) an improvement in feed status and feed consumption based on the flavor and palatability of the supplemented phytobiotics; ii) modulation of ruminal fermentation due to the antimicrobial effects; iii) an improvement in nutrient digestion and absorption with the augmentation of intestinal functions; and iv) direct and indirect anabolic activity on target tissues via the activation of endocrine and antioxidative defence systems. Phytobiotics are alternative to AGPs due to their strong antibacterial activity, potential to inhibit pathogenic bacteria, improvement in antioxidative status, and immune function.  Phytochemicals can be used in solid, dried and ground form or as extracts. Essential oils are volatile lipophilic substances obtained by cold extraction, and steam or alcohol distillation. Oleoresins are extracts derived by non-aqueous solvents.  Examples of phytochemicals used in livestock and poultry production are derived from ginger, garlic, turmeric, onion, mustard, cinnamaldehyde from cinnamon, pepper, grape sees, berries, etc. Phytonutrients used in ruminants as feed additives are mainly saponins, tannins and essential oils. Saponins are antibacterial and antiprotozoal, and also reduce ammonia nitrogen concentration. Tannins are found in most of the plants and having ability to bind and precipitate proteins. Essential oils are present in several plants and are used as growth enhancers. While using essential oils some of the factors to be taken into consideration are optimizing its composition, mutual interactions with other substance from food matrix, and its absorption in small intestine. Essential oils are use as modifiers of rumen fermentation and metabolic activities.

 

Antimicrobial peptides: Antimicrobial peptides (AMPs) are considered as most promising alternatives to antibiotics. AMPs are thought to have potential to treat infections associated with multidrug-resistant pathogens. These are small polypeptide molecules of around 12 to 50 amino acids, secreted as secondary metabolite and are found in all classes of living organisms. AMPs are found in tissues or mucous membranes. AMP are part of the natural innate immune system of animals and, in plants, form a defence system similar to the innate immunity observed in animals, protecting them from pathogens and pests. Some of the AMPs are having broad spectrum activities against bacteria, protozoa and viruses.  Over 5000 antimicrobial peptides have been described till date. In animals, AMPs are mostly found in the tissues and organs that are exposed to airborne pathogens.  The first animal-originated AMP isolated from rabbit leukocytes in 1956 is defensin.  Other examples are bombinin and lactoferrin. Insects and frog skin are the major sources of more different AMPs. Cecropins represent an important component of insect defence systems and synthetic cecropins exhibit a powerful inhibitory efficacy against E. coli, P. aeruginosa, Bacillus megatherium and Micrococcus luteus. Synthetic peptide of magainins from an African frog’s have antibacterial activity against E. coli, S. aureus and Klebsiella pneumonia. Bacteriocins like colicin and Nisin have been studied. Colicin is found to be effective on post weaning diarrhea in swine. Cecropin isolated from silkworm Hyalophora cecropia, have also been tested on pigs. Bovicin HC5 is isolated from Streptococcus bovis is having antibacterial activity. Microcin J25 has been used against Salmonella spp. and E. coli exhibiting antimicrobial activity, enhance growth performance, and improve fecal flora composition and intestinal structure.  Use of sublancin in broilers isolated from Bacillus subtilis 168, showed effect against Clostridium perfringensS. aureus and P. aeruginosa.

 

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Conclusion: Antimicrobial resistance is global problem and thus from food safety point, use of antimicrobials as growth promoters in livestock and poultry feed must be regulated. There is need for extensive research to find out novel alternatives for antibiotics and its commercial viability as animal feed supplement. Plant derived components as well as other biological non-toxic and non-infectious molecules shall be invented through integrated research. Research must be coupled with advance genomic and proteomic techniques in order to understand the modes of action of novel non-antibiotic compounds so that its feasibility and commercialization as animal feed supplement can be executed.

IMPORTANCE OF GROWTH PROMOTERS IN POULTRY

https://veterinaryresearch.biomedcentral.com/articles/10.1186/s13567-018-0562-6

Further reading:

Bahar, A. A., & Ren, D. (2013). Antimicrobial peptides. Pharmaceuticals (Basel, Switzerland)6 (12), 1543–1575.

Davani-Davari, D., Negahdaripour, M., Karimzadeh, I., Seifan, M., Mohkam, M., Masoumi, S. J., Berenjian, A., & Ghasemi, Y. (2019). Prebiotics: Definition, Types, Sources, Mechanisms, and Clinical Applications. Foods (Basel, Switzerland)8(3), 92.

Kikusato M. (2021). Phytobiotics to improve health and production of broiler chickens: functions beyond the antioxidant activity. Animal bioscience34(3), 345–353.

Lambo, M. T., Chang, X., & Liu, D. (2021). The Recent Trend in the Use of Multistrain Probiotics in Livestock Production: An Overview. Animals : an open access journal from MDPI11(10), 2805.

Lillehoj, H., Liu, Y., Calsamiglia, S., Fernandez-Miyakawa, M. E., Chi, F., Cravens, R. L., Oh, S., & Gay, C. G. (2018). Phytochemicals as antibiotic alternatives to promote growth and enhance host health. Veterinary research49(1), 76.

Markowiak, P., & Śliżewska, K. (2018). The role of probiotics, prebiotics and synbiotics in animal nutrition. Gut pathogens10, 21.

Micciche, A. C., Foley, S. L., Pavlidis, H. O., McIntyre, D. R., & Ricke, S. C. (2018). A Review of Prebiotics Against Salmonella in Poultry: Current and Future Potential for Microbiome Research Applications. Frontiers in veterinary science5, 191.

Pandey, K. R., Naik, S. R., & Vakil, B. V. (2015). Probiotics, prebiotics and synbiotics- a review. Journal of food science and technology52(12), 7577–7587.

Plaza-Diaz, J., Ruiz-Ojeda, F. J., Gil-Campos, M., & Gil, A. (2019). Mechanisms of Action of Probiotics. Advances in nutrition (Bethesda, Md.)10 (suppl_1), S49–S66.

Raiza F. Silveira, Cesar A. Roque-Borda, and Eduardo F. Vicente (2021). Antimicrobial peptides as a feed additive alternative to animal production, food safety and public health implications: An overview. Anim Nutr.  7(3): 896–904.

Ren, H., Vahjen, W., Dadi, T., Saliu, E. M., Boroojeni, F. G., & Zentek, J. (2019). Synergistic Effects of Probiotics and Phytobiotics on the Intestinal Microbiota in Young Broiler Chicken. Microorganisms7 (12), 684.

Rima, M., Rima, M., Fajloun, Z., Sabatier, J. M., Bechinger, B., & Naas, T. (2021). Antimicrobial Peptides: A Potent Alternative to Antibiotics. Antibiotics (Basel, Switzerland)10 (9), 1095.

Śliżewska, K., Markowiak-Kopeć, P., Żbikowski, A., & Szeleszczuk, P. (2020). The effect of synbiotic preparations on the intestinal microbiota and her metabolism in broiler chickens. Scientific reports10 (1), 4281.

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