Ways to Replace Antibiotic Growth Promoters

Angela Riemensperger of Biomin explains the mode of action and benefits of the company's product, which includes an organic acid blend, a phytochemical and a perforising substance.
calendar icon 28 October 2011
clock icon 7 minute read

Over many decades the usage of synthetically produced vitamins, antibiotics or antibiotic-based growth promoters (AGPs) was common practice. Especially after World War II and in the times during the economic boom in which the demand for food exceeded the supply, synthetically produced supplements were commonly used. The use of those substances offered the possibilities to improve animal performance and increase economical output of livestock-producing units. The increased productivity of those units played an important role especially in regions and continents where the availability of land is more limited. So the use of AGPs was especially widespread in Asia. Using AGPs gave Asian countries with only limited land resources the possibility to overcome the negative effects of overcrowding animal pens as diseases associated with overcrowding could be controlled. This resulted in a higher output per livestock unit, hence cheaper livestock production without having to invest in additional land.

However, the use of synthetically produced substances, especially AGPs, was soon found to have objectionable side-effects. Especially in times when food supply exceeded demand in most parts of the world and the term 'consumer society' most closely described the situation at the food market concerns regarding, more AGPs were used. As antibiotics have been used as growth promoters in animal feeds at sub-therapeutic levels for many years, reports about antibiotic resistance of pathogenic bacteria increased. Still today, every day new reports are published in newspapers worldwide reporting about the effects of antibiotic-resistant bacteria and germs and the consequence for human health. The World Health Organization (WHO) gave and still gives warnings, not only of unknown germs but also known pathogenic bacteria, which have become resistant or dangerous due to changes in their deoxyribonucleic acid (DNA).

Organic Acids as Alternatives

As the awareness of the danger of antibiotic resistant pathogens grew due to the excessive use of sub-therapeutic levels of antibiotics, research to find alternatives to AGPs was boosted and the market shifted away from pharmaceutical products and towards natural feed ingredients to secure the consumers' trust in animal products.

Acidifiers became the centre of attention, as they are among the best alternatives to antibiotics. The mode of action of organic acids is now quite well understood. Organic acids have been used for a long time in food and feed preservation. They exert their mode of action in feed as well as in the gastrointestinal (GI) tract of the animal. Organic acids lower the pH in feed and the GI tract, creating unfavourable conditions for harmful bacteria, resulting in reduced uptake by the host animal and a smaller bacterial load within the GI tract. The reduction in overall bacterial load, in turn, reduces the competition between the host and its gut microflora for nutrients.

Furthermore, organic acids reduce the buffering capacity of the feed, resulting in increased levels of hydrochloric acid (HCl) in the stomach and improved nutrient digestibility. The reduction in pH also increases pepsin activity and stimulates the secretion of pancreatic enzymes, which also improves nutrient digestibility. Furthermore, organic acids in their non-dissociated form, can penetrate the bacterial cell wall and disrupt the metabolism of bacteria by altering the internal pH of the cell. This forces the bacterial cell to restore the pH level – a process that consumes energy and may either prevent the growth or even kill the bacteria.

Overall, the reduction of the bacterial loads both within feed and the GI tract reduces health risks and associated economic losses and leads together with the stimulation of enzyme activity to improved growth performance. Positive effects of organic acids, including improved weight gain and feed efficiency, are described in detail in many publications. However, reported improvements on growth depend on the combination and dose of acids.

Broaden the Spectrum of Activity

Combining different organic acids and using acid blends instead of single acids became more common during recent decades as using combinations of organic acids broadens the spectrum of activity compared to single acids. The use of essential oils and their constituents in animal feed also became increasingly popular and these are now used in combination with other agents, e.g. organic acids, to improve the antimicrobial effect. Evidence shows essential oils and their constituents can act synergistically with organic acids.

One group of constituents of essential oils is the phytochemicals. Cinnamaldehyde, a constituent of cinnamon bark oil, has a particular mode of action and a narrower antimicrobial spectrum than other phytochemicals.

Human and veterinary medicine researchers are actively searching for drugs targeting the FtsZ protein as it plays a major role in the cell division of potentially harmful bacteria. FtsZ undergoes GTP-dependent polymerisation into filaments. These filaments assemble within the cell, where the cell division takes place, forming a polymeric structure known as the Z-ring, which is responsible for the cell division.

Cinnamaldehyde inhibits a number of processes within the cell, resulting in fewer Z-rings per unit cell length and hence cell elongation. It also decreases the amount of FtsZ available for binding and inhibits the GTP-ase activity of FtsZ, which explains the ability of cinnamaldehyde to depolymerise FtsZ polymers. As a result, bacterial load is decreased. However, it has to be highlighted that cinnamaldehyde acts specifically against pathogenic bacteria but spares beneficial bacteria.

Permeabilising Substances Better Combat Bacterial Challenge

Fighting the challenge of gram-negative bacteria is made more difficult because their outer membrane acts as a protective barrier for external agents, unlike gram-positive bacteria. However, it is possible to weaken the outer membrane with agents known as permeabilisers. Permeabilisers themselves may not be bacteriocidal but they may increase the activity of organic acids and phytochemicals, thus acting synergistically. Synergisms were shown in inhibition tests on different bacteria as shown in Figure 1. This figure indicates that the activity of organic acids and a phytochemical (antimicrobial mixture) was facilitated by the addition of a permeabilising substance – Biomin® perforizing substance – resulting in a synergism in the inhibition of bacteria.

Figure 1. Effect of an antimicrobial mixture (acid blend and phytochemical) combined with different permeabilising substances on the inhibition of bacteria

However, permeabilising substances act in different ways and it is important that the combination increases the permeability of the bacterial membrane. This only applies to a couple of permeabilising substances; they allow the organic acids to penetrate the cell wall, disturbing the pH balance in the cell. This explains the different levels of inhibition of bacteria by the permeablising substances shown in Figure 1.

In-vitro studies show that the synergy achieved by the inclusion of the permeabilising substance boosts the efficacy of the antimicrobial ingredients. This offers a different strategy to control bacteria. Furthermore, the decrease in bacterial load resulting from the inclusion of an organic acid blend, a phytochemical and the Biomin perforizing substance means that the host has less competition from the bacteria for nutrients. More nutrients available to the host improves animal performance and the economic benefits to the producer. This has also been demonstrated in in-vivo trials. Biomin has launched the natural growth promoter (NGP) as Biotronic® Top3.

October 2011

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