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Animal Health

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Animal Health
Wednesday, September 17, 2003 6:42:19 PM
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Replacing Antibiotic Growth Promoters 

H. M. Tan, Ph.D, Research Director & A.Y. Teo, Ph.D, Research Manager

Kemin Industries (Asia) Pte Limited



Antibiotics have been used as growth promoters in the food animal industry for several decades. These antimicrobial growth promoters (AGP's) allow animals to utilize feed more efficiently whilst protecting the animals from common infections. By 1995, some 90% of the antibiotics used in agriculture were reportedly used for the purpose of promoting growth and prophylaxis rather than as therapeutic agents. In recent years however, there has been increasing evidence that the high usage of AGP's has led the development of a reservoir of drug-resistant bacteria in food animals which in turn poses a threat to human health. The European Union has banned the use of AGP's and other countries will place increased regulatory restrictions on the use of these products. The World Health Organization has recommended the replacement of AGP's with safer alternatives and so there is a clear need to find alternatives to AGP's.


Mechanism of Action


The mechanism by which antibiotics at sub-therapeutic doses promote growth is not completely clear. However, AGP's reduce the normal intestinal flora which compete with the host for nutrients and which produce metabolites which are toxic and increase the mucosal gut turnover.  AGP's also reduce harmful gut bacteria that cause sub-clinical disease. Hence the AGP effect may be due to fewer normal gut microflora and less harmful or pathogenic bacteria. It has been estimated that some 6% of the net energy in a pig's diet may be lost due to the bacterial utilization of glucose in the small intestine. The growth-depressing metabolites produced by intestinal bacteria include phenolic/aromatic compounds such as phenol, p-cresol, indole along with ammonia resulting from microbial amino acid deamination and urea hydrolysis. Microbes can also deconjugate and dehydroxylate bile salts which affects lipid absorption and may also produce toxic degradation products that impair growth.


Intestinal bacteria play an important role in the development of the intestinal immune system. Antibiotics are thought to decrease immunogenic bacteria inhabiting the small intestine and hence prevent immunogenic stress and thereby promote growth. Antibiotics can also reduce the effects of gut microflora that contribute to a thicker gut wall, heavier intestinal weight and a reduced absorptive capacity. In general, antibiotics work to reduce the negative effects of the normal gut microflora such as competition for nutrients and energy, and to reduce harmful gut bacteria that retard animal performance. The net result is enhanced animal growth. Most of the AGP's are active against Gram-positive bacteria. A number of potential alternatives to AGP's have been identified over recent years.


Organic acids


Organic acids such as lactic and fumaric acids have been added to swine feeds for many decades now. They are believed to promote growth in young pigs via nutritional and anti-microbial means. Organic acids also exert preservative effects on the feed itself through inhibiting fungal and bacterial growth. Organic acids are widely used to inhibit pathogens such as Salmonella in feed ingredients, along the feed milling process and in finished feed. Organic acids in their un-dissociated form are able to pass through the bacterial cell membrane where they dissociate into H+ ions within the cell. The resultant pH reduction causes the cell to expend energy to pump out the extra H+ ions. The RCOO- anions produced can also disrupt DNA and protein synthesis. Organic acids are also beneficial in drinking water hygiene programs and have been shown to enhance growth in broiler chickens.




It has been estimated that 80% of poultry feed and 95% of swine feed do not contain enzymes. However, diets containing significant quantities of soluble non-starch polysaccharides are associated with increased fermentative activity in the small intestine in chickens. This can lead to the proliferation of anaerobic organisms such as Clostridium perfringens that can result in varying degrees of necrotic enteritis which in turn inhibits bird performance and can increase mortality. Enzymes that act on fibrous components in diets can help prevent microbial fermentation and the use of dietary enzymes has been observed to reduce the number of intestinal C. perfringens. Many other production benefits result from the use of enzyme supplementation of the feed.




These are non-digestible food ingredients that benefit the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon (eg. Bifidobacterium spp., Lactobacillus spp.) thus supporting improved animal performance. Prebiotics include mannose oligosaccharides, fructose oligosaccharides and lactulose and glucose oligosaccharides. Prebiotics in feed pass through the stomach relatively unaltered to reach the large intestine where their presence leads to an increase in the number of indigenous probiotic bacteria. They are believed to support microbial populations in the gut to change from "proteolytic" to more favourable "saccharolytic" activities. This results in reduced formation of toxic substances e.g. ammonia, hydrogen sulphide, indole and secondary bile metabolites. Prebiotics are also reported to improve mineral absorption, e.g. calcium and magnesium - probably by increasing their solubility in the intestine in association with the short chain volatile organic acids produced from microbial fermentation.


Microorganisms as Feed Additives


Microorganisms as feed additives are viable bacterial cell preparations or components of bacterial cells that have beneficial effects on the health of the host. Many of these microorganisms are lactic acid bacteria. These direct fed microorganisms are useful in the treatment of disturbed intestinal microflora and increased gut permeability, which are characteristic of many intestinal disorders. Such bacteria are able to survive gastric conditions to at least temporarily colonize the intestine. They have been reported to improve the growth rate and feed utilization in pigs, chicken and calves. The beneficial effects of such microorganisms range from displacement of harmful bacteria, reduction of bacterial urease activity, the synthesis of vitamins, and stimulatory effects on the immune system as well as a positive contribution to digestion.


Kemin Industries Asia has recently isolated a proprietary strain of a Bacillus sp. (CloSTATTM) that has shown specific in vitro and in vivo activity against Clostridial spp. including C. perfringens (Figures 1 and 2). The numbers of beneficial bacteria in the chicken's ileal contents (Lactobacillus spp. and Bifidobacterium spp.) were not decreased and indeed were found to be similar to that of an antibiotic treatment with a slightly better Bifidobacterium spp count and lower E.coli count (Figure 3). 


A broiler growth trial with Ross birds (New Zealand) indicated comparable performance with CloSTATTM and zinc bacitracin at 100ppm (Table 1). An elevated degree of phagocytosis in blood was measured in the chickens receiving CloSTATTM (Table 1) which suggests that these birds may be more immune responsive.


Table 1. Influence of CloSTATTM on 42 day weight gain, feed intake, feed conversion ratio (FCR) and blood phagocytosis index



Weight gain


Feed intake





Phagocytosis index


Negative control















Positive control

(100 mg/kg zinc bacitracin)
































A broiler growth trial with Arbor Acre birds (China) showed that birds receiving CloSTATTM were better able to withstand an E.coli challenge than the control birds (Table 2).  The negative control group dropped 5 points of FCR compared with no FCR change in the CloSTATTM treated birds. The CloSTATTM treated birds exhibited a 10 point and 15 point advantage in FCR over the negative control treatment for the unchallenged and challenged groups respectively as well as a growth rate advantage (Table 2).  In this trial, CloSTATTM also resulted in improved performance compared with the antibiotic treatment.


Table 2. Influence of CloSTATTM on 42 day weight gain and FCR without and with an E.coli challenge via drinking water on days 18, 28 and 38



Weight gain (g)


    Negative Control









    Positive Control

    (zinc bacitracin & colistin sulphate)





















These in vitro and in vivo results indicate that CloSTATTM can be used in broiler chicken production to help ensure a healthy intestinal microflora and so assist in disease prevention and health maintenance.



Figure 1.  Destructive effect of CloSTATTM on Clostridium perfringens (EM micrograph 29 500X), ie. disrupted cell membrane with leaking cytoplasm on the left (CloSTATTM) compared with control cells on the right




Figure 2. Influence of CloSTATTM and antibiotic (100ppm zinc bacitracin) treatments on ileal Clostridial populations of broiler chickens; values with different letters are significantly different (P<0.10).




Figure 3.  Influence of CloSTATTM and antibiotic (100ppm zinc bacitracin) treatments on ileal Lactobacillus spp., Bifidobacterium spp. and Escherichia coli populations of broiler chickens.

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