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2011, Vol. 6 No. 1, Article 76

 

Alternative Strategies to Antibiotic Growth Promoters - A review

S. Adil, M. T. Banday, G. A. Bhat and M. S. Mir*

 

Department of Livestock Production and Management
*Department of Veterinary Pathology
Faculty of Veterinary Sciences and Animal Husbandry
Sher-e-Kashmir University of Agricultural Sciences & Technology of Kashmir,
Shuhama-190006, India

 

*Corresponding Author; e-mail address: masoodmir1@gmail.com

 


ABSTRACT

Antibiotic growth promoters and antibiotic resistance are closed related. The increased concern about the potential for antibiotic resistant strains of bacteria has compelled the researchers to utility of other non therapeutic alternatives like enzymes, probiotics, prebiotics, herbs, essential oils, immunostimulants and organic acids as feed additives in animal production. Organic acids are not antibiotics but, if used correctly along with nutritional, managerial and biosecurity measures, they can prove powerful in maintaining the health of the GI-tract of poultry, thus improving their zootechnical performances. Due to antimicrobial effect, organic acids result in inhibition of intestinal bacteria leading to the reduced bacterial competition with the host for available nutrients and diminution in the level of toxic bacterial metabolites as a result of lessened bacterial fermentation resulting in the improvement of protein and energy digestibility; thereby ameliorate the performance of bird. The increased villus height in the small intestines induced by organic acids increases the absorptive intestinal surface, facilitates the nutrient absorption and growth performance. They decrease the pH value in different segments of gastro-intestinal tract which is conducive for the growth of favorable bacteria simultaneously hampering the growth of pathogenic bacteria which grow at relatively higher pH. The acid anion has been shown to complex with calcium, phosphorus, magnesium and zinc, which improves the digestibility of these minerals. Reduction in gastric pH following organic acid feeding increases pepsin activity and the peptides arising from pepsin proteolysis trigger the release of hormones, including gastrin and cholecystokinin, which regulate the digestion and absorption of proteins.

KEY WORDS

Antibiotic, growth promoter, organic acid, poultry.

INTRODUCTION

High levels of production and efficient feed conversion are the need of the modern livestock industry which to a certain extent could be achieved by the use of specific feed additives. Antibiotic feed additives as growth promoters have long been supplemented to poultry feed to stabilize the intestinal microbial flora, improve the general performances, and prevent some specific intestinal pathology (1-3). However, because of the growing concern over the transmission and proliferation of resistant bacteria via the food chain, the European Union (EU) in 2006 banned antibiotic growth promoters to be used as additives in animal nutrition. The antibiotic growth promoters have been under scrutiny for many years and have been removed from the market in many countries (4). Antibiotic growth promoters and antibiotic resistance are closely related.The increased concern about the potential for antibiotic resistant strains of bacteria has compelled the researchers to explore the utility of other non therapeutic alternatives like enzymes, probiotics, prebiotics, herbs, essential oils, immunostimulants and organic acids as feed additives in animal production. The focus of alternative strategies has been to prevent proliferation of pathogenic bacteria and modulation of indigenous bacteria so that the health, immune status and performance are improved (5). This publication presents a review on the growth promoting efficiency as well as mechanism of action of dietary organic acids in poultry.
Organic acids are considered to be any organic carboxylic acid including fatty acids and amino acids, of the general structure R-COOH. Not all of these acids have effects on gut microflora. In fact, the organic acids associated with specific antimicrobial activity are short chain acids (C1-C7) and are either simple, monocarboxylic acids such as formic, acetic, propionic and butyric acids, or carboxylic acids bearing an hydroxyl group (usually on the alpha carbon) such as lactic, malic, tartaric and citric acids. Salts of some of these acids have, also, been shown to have performance benefits. Other acids, such as sorbic and fumaric acids which are short chain carboxylic acids containing double bonds, have been observed to possess antifungal activity (6). Generally, two types of acidifiers are used, feed acidifiers and gut acidifiers. Feed acidifiers are pure organic acids which can be added to the feed by direct spraying. However, pure organic acids corrode the G.I. tract of poultry, and are, also, difficult to handle. Gut acidifiers are organic acid salts, such as ammonium di-propionate, potassium di-formate, sodium formate, calcium propionate, calcium lactate, ammonium formate etc., and have little or no corrosive effect on the G.I. tract of poultry (7). Organic acids are not antibiotics but, if used correctly along with nutritional, managerial and biosecurity measures, they can be a powerful tool in maintaining the health of the GI-tract of poultry, thus improving their zootechnical performances (8). If applied correctly, organic acids work in poultry, not only as a growth promoter but also as a meaningful tool of controlling all enteric bacteria, both pathogenic and non-pathogenic (9-10). Table 1 shows list and properties of commonly used dietary organic acids in poultry.

GROWTH PERFORMANCE

Patten and Waldroup (11) evaluated fumaric acid and reported that addition of 0.5 or 1.0% fumaric acid significantly improved body weights of broilers but did not influence feed utilization. Skinner et al. (12) reported that addition of 0.125% fumaric acid significantly improved 49-day body weight of females and average weight gain of both sexes with no effect on feed utilization. Also, higher body weight gain, feed intake and better feed efficiency due to organic acid supplementation has been reported (13). Christian Luckstadt et al. (14) observed that organic acid blend (3 kg inclusion rate per ton of feed) increased the growth of broiler chicken under controlled conditions without the use of anti-biotic growth promoters. The body weight of broilers at 6th wk. of age was significantly higher in the groups fed diet containing organic acid at 1 kg/ton or 1.5 kg/ton with a better feed conversion ratio noticed in the group containing organic acid at 1 kg/ton (15). Paul et al. (7) reported that ammonium formate or calcium propionate at the level of 3 g/kg feed increased the live weight and live weight gain and feed conversion ratio at day 21 in broiler chicken. Formic acid at the rate of 5,000 ppm and 10,000 ppm in the diet of chicken significantly improved feed conversion ratio and both levels were beneficial for improving the growth traits (16). Vieira et al. (17) reported improved body weight and feed conversion ratio with diets supplemented with a blend of organic acids (40% lactic, 7% acetic, 5% phosphoric and 1% butyric). Owens et al. (18) reported 12 % increase in total live weight gain and about 9 % improvement in gain feed ratio with diets supplemented with dietary organic acids. Improvement in live body weight, body weight gain and feed conversion ratio by organic acid supplementation (containing acetic acid, citric acid and lactic acid, each at 1.5 and 3.0 % in the diet) was also observed by Abdel-Fattah et al. (8).

MECHANISM OF ACTION

Antimicrobial Effect
The undissociated organic acid pass through the cell membrane of the bacteria and dissociate to form H+ ions which lower the pH of bacterial cell, causing the organism to use its energy, trying to restore the normal balance. Whereas RCOO- anions produced from the acid can disrupt DNA, hampering protein synthesis and putting the organism in stress. As a result the organism cannot multiply rapidly and decrease in number (19). The antibacterial effect of organic acids has been reported by many researchers. Sofos et al. (20) reported that the broilers on sorbic acid-containing feed had lower coliform counts in the duodenum, lower yeast and mold counts in the caeca, and higher Bacteroides counts in the caeca. Humphrey and Lanning (21) observed that 0.5% formic acid resulted in significant reduction in the isolation rate of Salmonella from laying hens, and also, a reduction in the incidence of infection in newly hatched chicks. Use of organic acid mixture containing formic and propionic acid decreased the Salmonella and lactic acid producing bacteria counts in hen’s crop (22). Alp et al. (23) reported that inclusion of antibiotic and an organic acid mixture containing lactic, fumaric, propionic, citric and formic acid separately or in combination reduced the Enterobacteriacae count in the ileum of broilers. Ramarao et al. (24) studied the efficacy of gut acidifier in broiler diets at the rate of 300 g/100 kg feed vis-à-vis use of antibacterial compounds. They observed that the total bacterial, coliform, and Escherichia coli counts in crop and caecal contents were low in broilers fed gut acidifier and opined that gut acidifier can safely replace antibacterial compounds in broiler chicken diets with beneficial effects on the intestinal bacterial colonization and resistance to E. coli challenge. Moharrery and Mahzonieh (25) described that malic acid have the potential for reduction of E. coli population in the intestines of broiler chicken. Thirumeignanam et al. (15) reported a decrease in the total bacterial load with concomitant increase in lactobacilli load as a result of dietary acidification. Organic acids mixture at the level of 0.2% in the diet of broilers significantly decreased total bacterial and gram negative bacterial counts compared to the basal diet (26). Fumaric and sorbic acid lowered the numbers of lactic acid bacteria and Coliforms in the ileum and caeca (27). Due to antimicrobial effect, organic acids result in inhibition of intestinal bacteria leading to the reduced bacterial competition with the host for available nutrients and diminution in the level of toxic bacterial metabolites as a result of lessened bacterial fermentation resulting in the improvement of protein and energy digestibility; thereby ameliorate the performance of bird.
Trophic Effects
Organic acids have direct stimulatory effect on the gastro-intestinal cell proliferation as has been reported by various workers with short chain fatty acids. The short chain fatty acids are believed to increase plasma glucagon-like peptide 2 (GLP-2) and ileal pro-glucagon mRNA, glucose transporter (GLUT2) expression and protein expression, which are potential signals mediating gut epithelial cell proliferation (28). LeBlay et al (29) and Fukunaga et al (30) also reported that short chain fatty acids can accelerate gut epithelial cell proliferation, thereby increase intestinal tissue weight and changing mucosal morphology. The beneficial effect of organic acids on the gastro-intestinal tract was observed by Denli et al (13) who reported that organic acids resulted in remarkable increase in the intestinal weight and length of broiler chicken. Also, Hernandez et al. (31) reported that formic acid increased the crypt depth of small intestines. Senkoylu et al. (32) reported increased villus height with combination of formic and propionic acids in broilers but found no effect on the thickness of lamina muscularis mucosae. Paul et al. (7), also, reported that the propionate, formate and lactate supplementation improved duodenal villus height. Similar results were observed by Garcia et al. (16) who found improved villus height with formic acid and also greater crypt depth but villus surface area was not influenced. Abdel-Fattah et al. (8) reported that the addition of any level and source of organic acids increased feed digestion and absorption as a result of increased small intestine density which is an indication of the intestinal villi dimension. The increased villus height in the small intestines has been related to a higher absorptive intestinal surface (33) which facilitates the nutrient absorption and hence, has a direct impact on growth performance.
Other Effects
Dietary supplementation of organic acids has been found to reduce the pH of crop, gizzard and duodenal contents (15). Abdel-Fattah et al. (8) reported that the pH values in different gastro-intestinal tract segments were decreased, although insignificant, with supplementation of organic acids irrespective of type and dose used. As per Bolton and Dewar (34) the effects of organic acids down the digestive tract gets diminished because of reduction in the concentration of acids as a result of absorption and metabolism. The lowered pH is conducive for the growth of favourable bacteria while it simultaneously hampers the growth of pathogenic bacteria which grow at relatively higher pH. This reduces bacterial competition with the host for available nutrients, thereby increasing the nutrient absorption. The acid anion has been shown to complex with calcium, phosphorus, magnesium and zinc, which improves the digestibility of these minerals (35-36). Organic acids serve as substrates in the intermediary metabolism (37) and lower chyme pH, consequently, enhancing the protein digestion (38). Reduction in gastric pH occurs following organic acid feeding which may increase the pepsin activity (39) and the peptides arising from pepsin proteolysis trigger the release of hormones, including gastrin and cholecystokinin, which regulate the digestion and absorption of protein (40).

CONCLUSION

In view of the concern for increased drug resistance among pathogens and drug carry over effects following use of subtherapeutic antibiotic growth promoters as feed additives, the non therapeutic alternatives like enzymes, probiotics, prebiotics, herbs, essential oils, immunostimulants and organic acids are the potential candidates as feed additives in animal production. Organic acids have shown versatility under experimental conditions. They exert growth promoting effect mainly because of their antibacterial activity, trophic effects, ph reducing property besides improving protein and mineral digestibility.

REFERENCES

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  2. Miles RD, Janky DM and Harms, RH. Virginiamycin and broiler performance. Poultry Science 1984; 63: 1218-1221.

  3. Waldroup A, Kaniawati S and Mauromoustakos A. Performance characteristics and microbiological aspects of broiler fed diets supplemented with organic acids. Journal of Food Protection 1995; 58: 482-489.

  4. Ratcliff J. Antibiotic bans-a European perspective. In Proceeding of the 47th Maryland Nutrition Conference for Food Manufacturers, March 22-24 2000;135-152.

  5. Ravindran V. Broiler nutrition in New Zealand - Challenges and Strategies. Accessed in 2006. www.feedinfo.com.

  6. Dibner JJ and Buttin P. Use of organic acids as a model to study the impact of gut microflora on nutrition and metabolism. Journal of Applied Poultry Research 2002;11: 453-463.

  7. Paul SK, Halder G, Mondal MK and Samanta G. Effect of Organic Acid Salt on the Performance and Gut Health of Broiler Chicken. The Journal of Poultry Science 2007;44(4): 389-395.

  8. Abdel-Fattah SA, El-Sanhoury MH, El-Mednay NM and Abdel-Azeem F. Thyroid activity, some blood constituents, organs morphology and performance of broiler chicks fed supplemental organic acids. International Journal of Poultry Science 2008;7(3): 215-222.

  9. Naidu AS. Natural food antimicrobial systems. CRC Press USA 2000; 431-462.

  10. Wolfenden AD, Vicente JL, Higgins JP, Andreatti Filho RL, Higgins SE, Hargis BM and Tellez G. Effect of Organic Acids and Probiotics on salmonella enteritidis Infection in Broiler Chickens. International Journal of Poultry Science 2007;6: 403-405.

  11. Patten JD and Waldroup PW. Use of organic acids in broiler diets. Poultry Science 1988;67: 1178–1182.

  12. Skinner JT, Izat AL and Waldroup PW. Fumaric acid enhances performance of broiler chickens. Poultry Science 1991;70: 1444-1447.

  13. Denli M, Okan F and Celik K. Effect of dietary probiotic, organic acid and antibiotic supplementation to diets on broiler performance and carcass yield. Pakistan Journal of Nutrition 2003;2: 89-91.

  14. Christian L, Nizamettin S, Hasan A and Aylin A. Acidifier – a modern alternative for anti-biotic free feeding in livestock production, with special focus on broiler production. Veterinaria Zootechnika 2004;27 (49): 91.

  15. Thirumeignanam, D, Swain RK, Mohanty SP and Pati PK. Effects of dietary supplementation of organic acids on performance of broiler chicken. Indian journal of animal nutrition 2006;23(1): 34-40.

  16. Garcia V, Catala-Gregori P, Hernandez F, Megias MD and Madrid J. Effect of Formic Acid and Plant Extracts on Growth, Nutrient Digestibility, Intestine Mucosa Morphology, and Meat Yield of Broilers. Journal of Applied Poultry Research 2007;16: 555–562.

  17. Vieira SL, Oyarzabal OA, Freitas DM, Berres J, Pena JEM, Torres CA and Coneglian JLB. Performance of Broilers Fed Diets Supplemented with Sanguinarine-Like Alkaloids and Organic Acids. Journal of Applied Poultry Research 2008;17: 128-133.

  18. Owens B, Tucker L, Collins MA and McCracken KJ. Effects of different feed additives alone or in combination on broiler performance, gut micro flora and ileal histology. British Poultry Science 2008;49(2): 202-12.

  19. Nursey I. Control of Salmonella. Kraftfutter 1997;10: 415-22

  20. Sofos JN, Fagerberg DJ and Quarles CL. Effects of sorbic acid feed fungistat on the intestinal microflora of floor-reared broiler chickens Poultry Science 1985;64(5) : 832-40

  21. Humphrey TJ and Lanning DG. The vertical transmission of salmonellas and formic acid treatment of chicken feed. A possible strategy for control. Epidemiology and Infection 1988;100(1): 43-49

  22. Thompson JL and Hinton M. Antibacterial activity of formic and propionic acids in the diet of hens on Salmonellas in the crop. British Poultry Science 1997;38: 59-65.

  23. Alp M, Kocabagli M, Kahraman R and Bostan K. Effects of dietary supplementation with organic acids and zinc bacitracin on ileal microflora, pH and performance in broilers. Turkish Journal of Veterinary Animal Science 1999;23: 451-455.

  24. Ramarao SV, Redddy MR, Raju MVLN and Panda AK. Growth, nutrient utilisation and immunocompetence in broiler chicken fed probiotic, gut acidifier and antibacterial compounds. Indian Journal of Poultry Science 2004;39(2): 125-130.

  25. Moharrery A and Mahzonieh M. Effect of malic acid on visceral characteristics and coliform counts in small intestine in the broiler and layer chickens. International Journal of Poultry Science 2005;4 (10): 761-764.

  26. Gunal M, Yayli G, Kaya O, Karahan N and Sulak O. The Effects of Antibiotic Growth Promoter, Probiotic or Organic Acid Supplementation on Performance, Intestinal Microflora and Tissue of Broilers. International Journal of Poultry Science 2006;5 (2): 149-155.

  27. Pirgozliev V, Murphy TC, Owens B, George J and McCann, ME. Fumaric and sorbic acid as additives in broiler feed. Research in Veterinary Science 84(3): 387-94.

  28. Tappenden KA and McBurney MI .Systemic short-chain fatty acids rapidly alter gastrointestinal structure, function, and expression of early response genes. Digestive Diseases and Sciences 1998;43: 1526–1536.

  29. Le Blay G, Blottiere HM, Ferrier L, LeFoll EC, Bonnet JP, Galmiche and Cherbut C. Short-chain fatty acids induce cytoskeletal and extracellular protein modification associated with modulation of proliferation on primary culture of rat intestinal smooth muscle cells. Digestive Disease Science 2000;45: 1623-1630.

  30. Fukunaga TM, Sasaki Y, Araki T, Okamoto T, Yasuoka T, Tsujikawa, Fujiyama Y and Bamba T. Effects of the soluble fibre pectin on intestinal cell proliferation, fecal short chain fatty acid production and microbial population. Digestion 2003;67: 42-49.

  31. Hernandez F, Garcia V, Madrid J, Orengo J, Catala P and Megias MD. Effect of formic acid on performance, digestibility, intestinal histomorphology and plasma metabolite levels of broiler chickens. British Poultry Science 2006;47(1): 50-56.

  32. Senkoylu N, Samli HE, Kanter M and Agma A. Influence of a combination of formic and propionic acids added to wheat- and barley-based diets on the performance and gut histomorphology of broiler chickens. Acta Veterinaria Hungarica 2007;55(4) : 479-90.

  33. Loddi MM., Maraes VMB, Nakaghi ISO, Tucci F, Hannas MI and Ariki JA. Mannan oligosaccharide and organic acids on performance and intestinal morphometric characteristics of broiler chickens. In proceedings of the 20th annual symposium 2004; Suppl. 1: 45.

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  35. Li DF, Che XR, Wang YQ, Hong C and Thacker PA. The effect of microbial phytase, vitamin D3 and citric acid on growth performance and phosphorus, nitrogen and calcium digestibility in growing swine. Animal Feed Science Technology 1988; 73: 173-186.

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TABLES

Table 1. List of acids and their properties

Acid

Chemical name

Formula

MW

pKa

 

Formic

Formic Acid

HCOOH

46.03

3.75

 

Acetic

Acetic Acid

CH3COOH

60.05

4.76

 

Propionic

2-Propanoic Acid

CH3CH2COOH

74.08

4.88

 

Butyric

Butanoic Acid

CH3CH2CH2COOH

88.12

4.82

 

Lactic

2-Hydroxypropanoic Acid

CH3CH(OH)COOH

90.08

3.83

 

Sorbic

2,4-Hexandienoic Acid

CH3CH:CHCH:CHCOOH

112.14

4.76

 

Fumaric

2-Butenedioic Acid

COOHCH:CHCOOH

116.07

3.02

 

HMB

2-Hydroxy-4-Methylthio Butanoic Acid

CH3SCH3CH2CH(OH)COOH

149.00

3.86

 

Malic

Hydroxybutanedioic Acid

COOHCH2CH(OH)COOH

134.09

3.40

 

Tartaric

2,3-Dihydroxy-Butanedioic Acid

COOHCH(OH)CH(OH)COOH

150.09

2.93

 

Citric

2-Hydroxy-1,2,3-Propanetricarboxylic Acid

COOHCH2C(OH)(COOH)CH2COOH

192.14

3.13

 

 

 


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