USE OF EUBIOTICS AS FEED ADDITIVES IN POULTRY & LIVESTOCK FOR MITIGATING THE AMR PROBLEMS

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USE OF EUBIOTICS AS FEED ADDITIVES IN POULTRY & LIVESTOCK FOR MITIGATING THE AMR PROBLEMS
Post no-1454 Dt-15/01/2020
Compiled & shared by-DR RAJESH KUMAR SINGH, JAMSHEDPUR, 9431309542,rajeshsinghvet@gmail.com

source-https://www.dsm.com/anh/en/feedtalks/eubiotics-definition-and-different-concepts.html

Eubiotics term refers to the maintenance of microflora in the intestinal tract. Eubiotics are mainly used to improve the health status as well as performance improvement in domesticated animals. They mostly include probiotics, prebiotics, organic acids and essential oils. The efficacy of the product is mainly dependent on the antimicrobial effects as well as their ability to alter the gut flora.
Antibiotic microbial resistance is considered to be one of the greatest threats to human health. In the United States, more than 2 million people are infected with antibiotic resistant bacteria annually, with 23,000 deaths as a direct result (Hampton, 2013). It predicted that by 2050, 10 million deaths world-wide will be attributable to antimicrobial resistance. India’s antimicrobial resistance problem is expected to get much worse because its consumption of antibiotics through animal sources is projected to nearly double during 2013-2030, according to a new global study on antibiotic use in farm animals. The study, by a team of international researchers, recommended regulatory caps on antibiotics in farm animals, limits on meat intake and user fees on the price of veterinary antibiotics to tackle this burgeoning issue globally.

According to the World Health Organisation, antimicrobial resistance (AMR) is the ability of a bacteria, virus and some parasites to stop antimicrobials like antibiotics, antivirals and antimalarials from working against it. This makes standard treatments ineffective and infections persistent and likely to spread to other people.

Eubiotics are gaining importance in developed countries with an increasing number of countries are limiting the use of antibiotics. Eubiotics helps in improving the immune system and thus plays asignificant role in the immune system. Eubiotics are the natural digestive stimulants, which create healthy balance of microflora in the gastrointestinal tract. For the activation of the immune response against diseases the inclusion of dietary organic acids has a eubiotic effect on the proliferation of indigenous lactic acid bacteria. It refers to feed additives such as prebiotics, probiotics, and organic acids. Eubiotics are good for digestive health and act as a substitute to antibiotics in feed. The eubiotic market is not only growing in the Europe and U.S but also in the developing countries such as China, India, and Brazil. In association with the global demand for safe human food and the production of eco-friendly, animal and fishery feed products eubiotics foods supplements have received significant attention in human as well as in animal feed additives.
The ban on antibiotics as a means to promote growth has been banned in regions such as Europe. This scenario has shifted focus to the development of new alternatives such as Eubiotics. Antibiotic traces have been found in meat thus adversely affecting human health. Due to adverse health effects of antibiotics, they become a topic of public controversy thus prompting governments to ban its usage. Livestock farmers are concerned with disease outbreaks such as swine flu, bird flu and various foot and mouth infections. The increasing concerns regarding quality and safety of meat as well as the established regulatory scenario discouraging antibiotics usage are prompting farmers to shift towards viable alternatives such as eubiotics.
Growing consumption of meat across the globe has increased the overall demand for it thus causing strain on the livestock industry. Also, consumer awareness about meat quality has grown in the recent past. To cater to this rising demand, livestock farmers try to raise yield by using various feed additives such as eubiotics. Limited availability of land resources as increasing shortage of water has put limitations on animal fodder production. Livestock farmers are trying to optimize feed utilization to increase output. Eubiotics complement optimized feed utilization and help in increasing yield as they prevent disease outbreak, maintaining gut health and increasing immunity.

About 20 years ago, the use of feed antibiotics and some other microbial compounds as performance enhancers became the target of increasing public criticism and a topic of political controversy (particularly in the EU countries). As the first country in Europe, Sweden banned the use of antimicrobial growth promoters as early as 1986. The use of avoparcin as a growth promoter was banned first in Denmark (May 1995), subsequently in Germany (January 1996) and finally in the remaining EU countries by April 1997. Based on various safety concerns and partly as a precautionary measure, the EU Council of Ministers suspended the authorization of four other feed antibiotics (spiramycin, tylosin, virginiamycin, Zn-bacitracin) by July 1999, and two quinoxaline derivatives (carbadox, olaquindox) by September 1999.
By January 2006, an EU ban on the use of the four remaining feed antibiotics, namely flavophospholipol, avilamycin, salinomycin-Na and monensin-Na (for beef cattle only) became effective. This total ban on the use of antibiotics as growth promoters has been integrated into a new EU regulation concerning feed additives (No. 1831/2003). Before the implementation of this complete ban on the use of antibiotic growth promoters (AGP), some experts attempted to assess possible effects on growth rate and feed conversion efficiency and discussed possible alternatives after the ban (Brufau, 2000; Verstegen & Schaafsma, 1999; Wenk, 2003; Witte et al., 2000). Serious problems were expected, particularly in early weaned piglets, with an average reduction in daily weight gain of 8% and a 5% increase in feed consumption per gain. In addition, a dramatic deterioration in the general health status of piglets was expected, resulting in a marked increase in prophylactic use of various therapeutic antibiotics. This trend has indeed been observed in many countries after the implementation of this general ban.

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Eubiotics: Alternative products for replacement of AGP

Before discussing which currently approved feed additives might be used as effective alternatives for replacement of AGP, it would be helpful to approach this topic from a scientific point of view, taking into account their principal mode of action. There is currently no doubt that their efficacy is primarily based on antimicrobial effects and their ability to influence and partly modify the composition and overall concentration of intestinal microflora. Taking this into consideration, we can see how various new and some traditional feed additives claim to affect the composition or activity of intestinal microbiota, such as organic acids, probiotics, prebiotics, essential oil compounds, and Zn and Cu compounds. In recent years, some of those have been described by the general term ‘Eubiotics’, which is related to the Greek term ‘Eubiosis’, referring to an optimal balance of microflora in the gastrointestinal tract. The main purpose of using such eubiotics is to maintain the intestinal eubiosis, which will result in an improved health status and performance in farm animals.
Eubiotic nutrition is a 3-step strategy:
• Step 1: Lliberate energy and proteins from feed by a multi-enzyme system.
• Step 2: Maximise nutrient absorption by lysolecithins.
• Step 3: Manage an optimal GI-microflora to stimulate gut health, which can be achieved with α-monoglycerides.

A multi-enzyme approach

To gain full benefit from diets containing cereal grains and high fibre plant proteins, a multi-enzyme system containing fibre-degrading enzymes such as xylanase, beta-glucanase, cellulase and pectinase are needed. Due to the presence of non-digestible oligosaccharides in leguminous seeds, also alpha-galactosidase and beta-mannanase are needed. Moreover, the production of endogenous enzymes in young animals may not yet be sufficient for digesting all plant proteins and the high level of starch in current diets. Therefore, protease and alpha-amylase supplementation is needed to maximise the utilisation of proteins and starch.
A multi-enzyme system is beneficial to current broiler diets. This led Framelco to develop Fra Octazyme Dry, a product that contains 8 active enzymes:
1. xylanase,
2. beta-glucanase,
3. cellulase,
4. pectinase,
5. alpha-galactosidase,
6. mannanase,
7. alpha-amylase
8. protease.
Optionally phytase may be added to maximise the utilisation on the phytine phosphorous from plant material.

Maximise nutrient absorption

When feed has been properly broken down into single nutrients, they need to be absorbed in the small intestine. Nutritional emulsifiers, like hydrolysed lecithins (lysolecithins) are beneficial in this matter. Hydrolysed soy lecithins contain high levels of lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE). LPC and LPE are both important components of the lipid bilayer of cell membranes and have the ability to fluidise this membrane allowing an easier absorption of nutrients, fats and fatty acids. Hence, the second step in the Eubiotic nutrition is the addition of lysolecithins, like Fra LeciMax Dry.

Managing the gastro-intestinal microflora

Short- and medium chain fatty acids (SCFA & MCFA) have been widely used for their beneficial effects on general animal health and performance. According to scientific research, α-monoglycerides of these fatty acids are much more powerful in their antibacterial effect.
As α-monoglycerides of SCFA are more active against gram-negative bacteria and the α-monoglycerides of MCFA more towards gram-positive bacteria, products such as Fra Gut Balance produced by Framelco have a broad spectrum of antibacterial effect. Moreover, α-monoglycerides are stable molecules that are active through the entire GIT. This results in an optimal microbial gut balance and gut health, improving health and performances of food producing animals. The use of alpha-monoglycerides is a key strategy in Eubiotic nutrition.

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Based on the type, the Eubiotics is further classified into probiotics, prebiotics, exogenous enzymes, organic acids, essential oils, and others.

Organic acids

Organic acids and some of their salts have been added to compound feeds, for many years, in particular for early weaned piglets. The potential of diet acidification in order to overcome digestive insufficiency and post-weaning problems in piglets has been studied for a long time. The efficacy of fumaric acid, citric acid, formic acid, lactic acid, sorbic acid and also of some salts (Ca-formate, Na-formate) has been demonstrated. However, these compounds are officially approved in the EU as feed preservatives, however, some of them are used primarily for the stabilization of health status and performance enhancement at the dietary inclusion levels of 0.5 to 2.0%. In order to reduce dietary inclusion levels and enhance their efficacy at economically feasible costs, either blends of organic acids or coated forms have appeared on the market in recent years. Various hypotheses regarding the mode of action and beneficial effects of organic acids have been described in the literature, such as:
• Improvement of palatability and reduction of diet pH;
• Antimicrobial and preservative effects in the feed;
• Reduction of gastric pH and enhancement of pepsin activity;
• Effects on microflora in the gastro-intestinal tract, reduction of coliforms and diarrhea;
• Increased digestibility of nutrients.
Since July 2001, potassium diformate has been approved as a feed additive in the EU and included in the zootechnical additive group. In May 2003, benzoic acid has been approved as a feed additive for growing-finishing pigs at the inclusion levels of 0.5 to 1.0% and included in the acidity regulator group. Due to its specific metabolism, this organic acid shows multiple beneficial effects (Broz, 2004). Dietary supplementation results in a decrease in urinary pH accompanied by a reduction in ammonia emission and improved growth performance. Since November 2006, benzoic acid at the inclusion level of 0.5% has also been approved for use in weaned piglets, as a zootechnical additive. Due to its antibacterial activity and slower absorption, dietary benzoic acid is also capable of significantly reducing the density and metabolic activity of intestinal microflora in piglets (Kluge et al, 2006; Broz & Paulus, 2006). Balance trials have confirmed significant beneficial effects on the apparent ileal digestibility of dietary energy and nitrogen, as well as a significant increase in nitrogen retention. In a series of performance trials, benzoic acid at 0.5% has repeatedly resulted in significant improvements in piglet growth rates after weaning.

Probiotics

Probiotics are viable microorganisms that are used as feed additives in monogastric animals. The probiotic concept is primarily based on the assumption that direct feeding of microbial cultures may affect the composition of intestinal microbiota. Selected strains of microorganisms, believed to possess beneficial effects on digestive processes or animal health are used. Enterococcus faecium and spore-forming Bacillus spp. are the most frequently utilized probiotic microorganisms for swine. Probiotics were established as a new category of feed additives in the EU about twenty years ago and at present, there are more than 40 preparations approved for animal nutrition. In the US, such products are usually marketed as direct-fed microbials.
The modes of action of probiotics are not well characterized and therefore various hypotheses have been suggested in the literature :
• Competitive adhesion of probiotic microorganisms to epithelial receptors may prevent the attachment of pathogenic bacteria (rational behind “competitive exclusion”);
• Aggregation of probiotics and pathogenic bacteria;
• Competition for nutrients between probiotic and undesired bacteria;
• Increased synthesis of lactic acid and reduction of intestinal pH;
• Production of specific antibacterial substances;
• Reduced production of toxic amines and decrease of ammonia level in the gastro-intestinal tract.
• Beneficial effects on the intestinal immune system, an improved intestinal defense against viral infections.
Several beneficial claims have been established for microbial probiotics, but it is not always possible to provide sufficient scientific evidence to back up these claims. They usually show usually only limited and variable growth-promoting effects and in general, the “probiotic effect” is not as consistent as in case of AGP.

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Prebiotics

The concept of prebiotics was first developed and introduced by Gibson and Roberfroid (1995) in human nutrition. It is based on the feeding of certain non-digestible oligosaccharides in order to control or manipulate microbial composition and/or activity, thereby assisting to maintain a beneficial microflora (Zimmermann et al, 2001). Initially, various oligosaccharides, which are natural constituents of plants were considered as potential probiotic products for animal nutrition, such as fructo-oligosaccharides, xylo-oligosaccharides, isomalto-oligosaccharides, trans-galactooligosaccharides (TOS), mannan-oligosaccharides and some fructans (inulin, lactulose). Dietary inclusion levels of potential prebiotics are usually 0.1 to 0.5% and many suppliers intend to market them as feed ingredients, claiming selective regulation of intestinal microflora, reduction of pathogens and promotion of beneficial microorganisms (e.g. Bifidobacteria, Lactobacilli). Roberfroid (2007) revisited this concept in human nutrition and concluded, that only 2 dietary non-digestible oligosaccharides, namely inulin and TOS (mixture of oligosaccharides derived from lactulose by enzymatic transglycosylation) fulfill all the criteria necessary for prebiotic classification. They include resistance to gastric acidity, to hydrolysis by digestive enzymes and to gastrointestinal absorption, fermentation by intestinal microflora and selective stimulation of the growth and/or activity of those intestinal bacteria that contribute to health and well-being. Unfortunately, the effects of such ingredients on performance of farm animals such as poultry and swine are not consistent.

Essential oil compounds

Another group of feed additives showing a potential for the replacement of AGP are essential oil compounds, which are active ingredients present in various plants, and spices (e.g. thymol, carvacrol, eugenol). Due to their antibacterial activity they might be able to modify the composition of intestinal microflora and to exert beneficial effects on performance of poultry and swine. At present all active compounds are listed in the flavouring agent group under EU legislation. In poultry, several authors have reported an in vivo effect on microflora by specific formulations of EOC: Hume (2006) showed an overall modification of the microflora, Mitsch (2004) a reduction of Clostridium perfringens and Jang (2007) a decrease in E.coli numbers in broiler ileo-cecal digesta. Additionally, increases in digestive enzyme production have been identified by Lee (2003) and Jang (2007). However, a positive impact on performance has seldom been reported with EOC alone. Instead, a combination of benzoic acid and EOC has recently been shown to improve the performances of broilers (Weber, 2012) and turkeys (Giannenas, 2014). Although the efficacy of EOC in poultry show promise, more research is required in swine to better understand the benefits of these essential oil compounds either alone or in combination.

Future innovative concepts

Substantial research has been conducted over the past few years to evaluate the potential of alternative antimicrobial agents for replacement of AGP. Some natural compounds such as lactoferrin, lysozyme, bacteriocins and antimicrobial peptides appear to result in beneficial effects. Lactoferrin, isolated from bovine milk was evaluated as a potential feed additive in early weaned piglets and significant positive effects on performance parameters were observed at a 2000ppm inclusion level. However, due to its relatively high production costs, practical use in animal nutrition is currently not feasible. Lysozyme (1,4-beta-N-acetylmuramidase) is an enzyme exhibiting antibacterial properties. It is present at low concentrations in animal products such as milk, hen eggs and also in many tissues. Recently published results confirmed that dietary addition of lysozyme improved growth performance of young piglets and it could also be considered as an alternative to AGP. Bacteriocins and antimicrobial proteins have also attracted attention as potential substitutes, but some regulatory issues, particularly in the EU, in addition to their high production costs are factors that might prevent their practical application in the near future.

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