Alternatives to In-feed Anbiotics: do we really have some alternatives?

Antibiotic growth promoters (AGP) have been used sub-therapeutically in poultry and other livestock species for maintaining health and improving performance for more than 60 years. After the ban imposed in European Union on use of AGP in animal feeds and growing demand for antibiotic free animal products in other parts of the world, there is need to find alternative substances that can ensure animal health and performance, without residual effects on human health. Some potential alternatives are organic acids, phytogenic products, probiotics, prebiotics, enzymes, bacteriophages, antibodies, minerals and their salts. Some of these potential alternatives have been tested in live poultry flocks; others have only been tested in laboratory. This paper summarises the results of contemporary research work done on application of these substances on poultry health and performance.

Antibiotics have been successfully used in animal production since their discovery for maintaining health and improving performance and liveability. The risk of bacteria acquiring resistance to specific antibiotics possibly by continuous sub-therapeutical administration of AGP in animal feed led to a ban on subtherapeutic use of AGP in animal diets in European Union (EU) since January 2006. As a result of this ban in EU and growing pressure on animal producers in other parts of world, alternative substances and strategies for animal growth promotion and disease prevention are being investigated. These range from different natural products, purified extracts, combination of various products, to direct fed microbes, bacteriophages and nano-particles, as well as adoption of different husbandry practices.

In-feed antibiotics were supposed to increase growth rate and feed efficiency of poultry and other animals as a result of improved gut health, nutrient utilization and improved feed conversion efficiency (Visek, 1978). There are a number of substances and different strategies which are under investigation to replace AGP after ban imposed on their use in diets. Most investigated substances include organic acids, different phytogenic products, pro- and prebiotics, enzymes, bacteriophages, antibodies, vaccines, minerals and their salts. Organic acids and their slats when incorporated in diets, prevent feed degradation, improve digestibility of nutrients, reduce pH in the digesta and are able to suppress the growth of undesired micro-organisms mainly in the upper part of th e digestive tract.
Organic acids can be metabolized and represent therefore an energy source. They can improve the hygienic quality of meat and egg quality with the suppression of undesired micro-organisms like Salmonella and Campylobacter (Byrd et al., 2001 and Hadorn et al., 2001). After penetrating the bacterial cells they dissociate, releasing a hydrogen ion which destroys the acid-base balance and disrupts biochemical activities causing cell death. The dead cells display disruption of cytoplasm, a sudden pH drop and cell membrane leakage (Jordan et al. 1999). In the gastro-ileal region, organic acids inhibit undesirable microbes such as E. coli and Salmonella, hence reducing the proliferation and/or colonisation of potentially pathogenic bacteria and thus reduce diarrhoea incidences (Liu, 2001). Supplementation of organic acid combination (200mg lactic acid, 250mg formic acid, and 80mg propionic acid/kg feed) reduced the incidence of Salmonella spp. and prevented food poisoning and early spoilage of chicken meat (Aksit et al., 2006). Broiler diets supplemented with 5 or 10 ppm formic acid showed similar effects as avilamycin in improving growth and nutrient apparent ileal digestibility (Garcia, 2007). Table 1 shows effects of certain organic acids in poultry.

 Table 1. Effect of certain organic acids on poultry performance

Phytogenic products include substances of plant origin. In the absence of AGP, plant products (herbs and spices) and their extracts (ethanol and/or water extracts, essential oils) can be valuable alternatives as they play a significant role in health and nutrition. Plant extracts and their essential oils have a wide range of activities, including inhibitory action on pathogens, effects on physio-pathologies (e.g. anti-inflammatory, anti-diarrhoea properties) and activity in different body systems, e.g. endocrine and immune system (Francois, 2006). Beneficial effects of herbs or botanicals in farm animals may arise from activation of feed intake and digestive secretions, immune stimulation, anti-bacterial, coccidiostatic, anthelmintic, antiviral or anti-inflammatory activity and particularly antioxidant properties. Most of secondary plant metabolites like flavonoids and glucosinolates have b een suggested to act as antibiotics or as antioxidants. Macrophage activation is the primary means by which herbs modulate the immune system (Groom, 2007).

Some resources claim that phytogenic feed additives account for 10% share of the global feed additive market (Anonymous, 2008a). Windisch and co-workers (2007) found that experimental comparison of phytogenic feed additives with antibiotics and organic acids showed similar effects on gut, such as reduced bacterial colony counts, less fermentation products (including ammonia and biogenic amines), less activity of gut associated lymphatic system, and a greater pre-cecal nutrient digestion, probably reflecting an overall improved gut equilibrium. A combination of different herbal products with extracts from cinnamon, garlic, lemon, and rosemary showed positive results against Histomoniasis (infectious entero- hepatitis, blackhead) in turkey poults in vivo as it reduced mortality (Hafez and Hauck, 2006), but, in a field study it did not show satisfactory results (Chossat, 2002). Due to their antimicrobial properties, essential oils derived from several spices and herbs could be used as alternative feed additives in animal nutrition. A variety of herbs and their products that are under investigation for a future role in animal feeds includes Echinacea spp., Garlic, Ginseng, thyme, Cinnamon, Oregano, Nigella sativa, rosemary, olive oil, Sanguinaria Canadensis roots, Rhubarb root, Sage, Curcuma longa, Chillies, peper and turmeric.

The desired activity of phytogenic products is not always constant, as affected by variety, environmental growth conditions, harvesting time and state of maturity, method and duration of conservation and storage, extraction method, as well as possible synergistic or antagonistic effects, anti-nutritional factors or microbial contamination.
Probiotics are defined as live microbial supplements, which benefit the host animal by improving its intestinal microbial balance. Probiotic preparations may consist of single or a combination of several bacteria and yeast species. Commonly used commercial probiotics contain lactic acid producers such as Lactobacilli, Bifidobacteria and Streptococci. Along with lactic acid probiotics also produce some other metabolites such as hydrogen peroxide, carbon dioxide, diacetyl and bacteriocins (A-Awere and Lunen, 2005). Postulated mechanism of probiotic enhancement of poultry health and productivity may be by prevention of pathogenic colonization by competitive exclusion, maintenance of epithelial barrier integrity, transport of nutrient and enhancement of intestinal immunity (Chickowski, 2007). Probiotics offer the potential to increase normal micro-flora population by selectively excluding specific pathogenic bacteria (e.g., Salmonella, E. coli, Campylobacter, Listeria, and Clostridium) in the gut (Gibson and Fuller, 2000; Sanders 2000; Biernasiak, 2007).
Prebiotics are non digestible food ingredients that beneficially affect the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria already resident in the colon (Gibson and Roberfroid, 1995). Prebiotics include non digestible oligosaccharides such as fructo-oligosacchardies, mannan-oligosaccharides, soybean oligosaccharides, galacto-oligosaccharides, lactulose, and lactitol, which are dietary carbohydrates and proposed to have good prebiotics properties (A-Awere and Lunen, 2005). Some other products being used as prebiotics include gluco-oligosaccharides, isomalto- oligosaccharides, and xylose oligosaccharides (Gibson and Fuller, 2000).

NSP (non starch polysaccharides) enzymes are helpful in digestion of NSP substances like arabinoxylans, beta-glucans, pectins and cellulose present in cereals. NSP are partially soluble in water resulting in the formation of gel solutions, which increase gut viscosity leading to impairment in the function of digestive enzymes, decreased digesta flow and absorption of nutrients, and sticky droppings. Addition of NSP enzymes in the diets reduces the adverse effects of the NSP and phytic acids, helps in digestion of NSPs for energy production, improves the nutritive value, economises poultry production and reduces environmental pollution (Panda et al., 2006).

Bacteriophages are viruses that infect and kill bacteria. They do not infect animal and plant cells, which makes them a potentially safe alternative to antibiotics. An intramuscular injection of bacteriophages given 24 or 48 h after the birds were challenged protected the birds from severe E. col i infection (Huff et al., 2005). Some limitations in their use include their specificity, uncertainty over regulatory acceptance of bacteriophage, concern over protection of proprietary rights of bacteriophage products, fragile activity, and practical routes of administration of bacteriophage in animal production systems (Huff et al., 2004).

Antibodies like egg yolk antibodies and serum antibodies can be a source of passive immunization. Injecting hatching eggs with monoclonal antibodies to adipocytes can reduce fat deposits in market age broilers (Cartwright et al., 2000). The monoclonal antibodies could be injected into fertile hatching eggs by an automated egg injection system. There may be future potential for multi-purpose antibodies contained in spray-dried eggs from hens injected with multiple antigens to accomplish specific purposes (e.g. anti-E. coli , Salmonella, and Campylobacter antibodies).

Mineral and their salts: Micro minerals are essential part of metabolic processes taking place in the body. If they are administered at higher levels than required, they serve to promote growth and maintain health in broilers and turkeys. Copper sulphate pentahydrate or tribasic copper chloride is often used at higher than minimum requirement levels for growth promotion in broiler chickens and turkeys. But, increased copper supplementation generally results in increased liver copper concentrations. Similarly zinc and selenium salts when administered in poultry diets are reported to enhance performance and immunity.
Nanoparticles are normally 1 to 100 nanometers. Some nanoparticles have been built that are supposed to mimic the host cell surface in poultry and lock the targeted pathogens. The particles then bind together and are purged through the feces (Anonymous, 2008b).

In the past, intensive poultry production was mostly dependent on antibiotics. However, AGP ban in EU and increasing market demand of antibiotic free animal products in other parts of the world has changed the focus towards natural substances. Many substances and products are under investigation. Some of these products showed better results in laboratory, but failed to show comparable results in field studies. The comparison of one alternative with another is complex and depends on a various factors. Some substances are effective when used alone but their combination with others does not always show synergistic effects. At present there is no specific substance that can be claimed as effective as AGP. However, a combination of different products and adopting proper husbandry practices can help in maintaining health and improving performance of poultry birds.

Adjiri-Awere, A., and Van Lunen, T.A., (2005). Can J. Anim. Sci. 85 :117-130.
Anonymous, (2008a). Delacon. Feed info news service (19.Feb).
Anonymous, (2008b). http://www.allaboutfeed.net/news/id102- 40104/nanotechnology_for_intelligent_bird_feed.htm
Askit, M., Göksoy, E., Kök, Filiz. Özdemir, D., and Özdogan, M. (2006). Arch. Geflügelk. 70 (4)168-173.
Biernasiak, J., Silizewska, K., Libudzisz, Z., Smulikowska, S. (2007). Pol J Food Nutr Sci 57(4): 19-25.
Botsoglou, N.A., Christaki, E., Florou-Paneri, , P., Giannenas, I., Papageorgiou, G. , and Spais, A.B. (2004) South African Journal of Animal Science 34 (1) 52-61.
Byrd, J.A.; Hargis, B.M. (2001). Poultry Science, 80: 278-283.
Cartwright, A. L., Y. J. Wu, and Valdez-Corcoran, M.(2000). in: Proc. Maryland Nutr. Conf., March 22-24. pp 111-134
Casewell, M., Friis, C., Marco, E., McMullin, P and Phillips, I. (2003). Journal of Antimicrobial Chemotherapy 52, 159–161.
Chossat L. 2002. essai de prevention par phytotherapie. Lyon.
Chichlowsky, M., Croom, J., McBride, B.M., Havenstein, G.B., and Koci, M.D. (2007). Int’l J Poult Sci 6(10):694-704.
Francois, R., (2006): Poult. Int. Feb, pp 28-31.
Garcia, V., Gregori, C., Hernandez, F., Megias, M.D. and Madrid, J. (2007). J. Appl. Poult Res. 16: 555-562.
Hadorn, R., Wiedmer, H. and Feuerstein, D. 2001. Archiv für Geflügelk, 65: 22-27.
Hafez, H.M., and Hauck, R.D., (2006). Archives of Animal Nutrition, 60(5): 436 – 442. Huff, W. E.,G.R.
Huff, N.C. Rath, J.M.Balog, and Donoghue, A.M.(2004). in Preharvest and postharvest Food Safety Contemporary Issues and Future Directions. pp 365-374 Huff, W.E.,
Huff, G.R., Rath, , N.C., Balog, J.M. and Donoghue, A. M.,(2005). Poult Sci 84:655–659.
D. Pillai, T. D. Phillips, R. L Ziprin, ed. Blackwell Publishing,Ames, IA.
Gibson, G. R., and R. Fuller. 2000. J. Nutr. 130:391S–395S.
Gibson, G. R., and M. B. Roberfroid. 1995. J. Nutr. 125:1401–1412.
Groom, S.N., Johns, T., and Oldfield, P.R. (2007). J Medicinal food 10(1), 73-79
Jordan, D., McEwen, S.A., Lammerding, A.M., McNab, W.B. and Wilson, J.B. (1999). Preventative Veterinary Medicine 41, 55–74.
Liu Y, G., (2001) Feed mix 9 (6) 26-29.
Panda, K., Rao S. V.R., and Raju, M.V.L.N., (2006) Feed Tech 8, 23-26
Sanders, M.E., (2000). J. Nutr. 130: 384S–390S.
Visek, W.J., (1978) J. Anim Sci. 46: 1447-1469.
Windisch, W.M.,Schedle, K., Plitzner, C. and Kroismayr A.(2007). doi:10.2527/jas.2007-0459.