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The use of medium chain fatty acids as alternatives to antibiotic use in pigs Wouter Naeyaert, Product Manager Pigs, Nuscience Worldwide there is a clear demand to reduce the antibiotic use in livestock farming to reduce the risk for antibiotic resistance. Medium chain fatty acids are well known to exert excellent antimicrobial properties. For this reason they are used for a long time as alternative to antibiotics in piglet nutrition. However the properties of medium chain fatty acids go far beyond their antimicrobial effect. In this way they are an excellent option to reduce the antibiotic use in pigs. Urgent time to act The indiscriminate use of antibiotics in livestock production has been the subject of criticism by a lot of consumer organizations and governments. Consumers worldwide increasingly ask for healthy food from antibiotic-free raised animals. This as they want to preserve the ever-diminishing arsenal of effective antimicrobials in humans. If we don’t do anything, it is estimated that by 2050 yearly 10 million people will die due to antimicrobial resistance. This is far more than the actual number of deaths due to road traffic accidents or cancer! There is a huge need for a transition from a preventive antibiotic use, to a responsible therapeutic use of antibiotics. To do this we need alternatives to reduce the antibiotic use in a responsible way, without compromising food safety and human health as well as animal health, welfare and productivity. Improving gut health is the key Maintaining a good gut health is essential to a low antibiotic use and good growth performances. As gut health is an extremely complex matter, no clear definition is available. However it is clear that gut health is an interaction between the diet, the gut mucosa and the gut microflora which should provide an effective digestion and absorption of the feed, the absence of gut diseases, a stable gut microbiota and an effective immune status. The importance of a healthy gut cannot be underestimated. The gut surface is 200 times higher than the skin surface. And this surface has an extremely difficult and contradicting function: absorbing nutrients as efficient as possible, while reducing the entrance of noxious substances as much as possible. As the gut contains in fact 10 times more bacteria than the number of body cells, this is an extremely difficult task! In this way it is not strange that 20-35% of the energy- and amino acid requirements of the pig go to the gut. As 70% of the immune cells are concentrated around the gut, it is clear that gut health is also essential to improve immunity of the animals. The importance of gut health is also widely recognized in academical research. In 1999, 250 articles were published on gut health of pigs. Last year in 2015, this number increased to over 750 articles. Taking all of this into account, it is clear that reducing antibiotic use is only possible by maintaining a good gut health. Of course gut health is difficult to measure, but an improved gut health can easily be seen in technical and health parameters. Examples are: improved growth performances, reduced FCR, less prevalence of pathogens (E. Coli, Brachyspira, Lawsonia, Salmonella), improved immunity, lower need for antibiotic use, and a lower mortality. Medium chain fatty acids as gut microbiota regulator Medium chain fatty acids (MCFA) are saturated fatty acids consisting of aliphatic tails of total chain length of either 6 (caproic acid), 8 (caprylic acid), 10 (capric acid) or 12 (lauric acid) carbon atoms and a polar head. The use of free (so not coated, micro-encapsulated or esterified) MCFA as a functional feed ingredient is an effective way to reduce the antibiotic use in pigs. Free MCFA provide an early pathogen barrier in the stomach of the animal. This is an advantage over MCFA esterified mono, di- and triglycerides, which are only gradually active in the intestinal tract after endogenous lipase releases the free MCFA molecules. Figure 1: Chemical structure of medium chain fatty acids In the low pH environment of the stomach, un-dissociated MCFA are capable of penetrating the phospholipid bilayer of the bacterial cell membrane, thereby destabilizing it. This results in leaking of bacterial cell content on the one hand and entering of MCFA in the bacterial cells on the other hand. Inside the bacterial cell, MCFA’s encounter a near-neutral environment resulting in accumulation of dissociated MCFA molecules and protons in the bacterial cytoplasm. Dissociated MCFA’s will intercalate with the bacterial DNA, thereby inhibiting DNA replication and thus bacterial growth. Intracellular acidification and inhibition of DNA replication will eventually lead to killing of the bacterium. Thanks to their specific chemical properties, medium chain fatty acids have a much higher antimicrobial activity compared to other acids. MCFA clearly show lower minimal inhibitory concentrations (MIC) when compared to short chain and long chain fatty acids (Table 1). Table 1: Minimal inhibitory concentrations (MIC) of different organic acids for different bacteria, expressed in g/kg Bacterial strain Propionic acid Butyric acid Formic MCFA Bacillus cereus >10 >10 >10 2.5 Campylobacter jejuni 5 5 5 0.5 Clostridium perfringens 5 >10 2.5 0.5 Enterococcus faecalis >10 >10 >10 2.5 Escherichia coli >10 >10 >10 5 Salmonella enteritidis >10 >10 >10 5 Staphylococcus aureus 5 >10 >10 2.5 >10 >10 >10 2.5 Brachyspira hyodysenteriae Not only do these medium chain fatty acids kill pathogens, they also alter virulence of pathogens. Even at non-bactericidal concentrations, MCFA’s can have a dramatic effect on pathogen persistence. By reducing the virulence of bacterial pathogens like Clostridium and Salmonella, the outcome of disease is altered and intestinal and systemic colonization is reduced, as shown in scientific trials. The combination of these antibacterial actions ensures that the beneficial microbial system of the gut will be largely unaffected. MCFA clearly shift the balance in the gut from Enterobacteriaceae to the beneficial Lactobacilli in the ileum of piglets (Figure 1). Changes in bacterial composition in the ileum of piglets when adding MCFA to the feed 8 LOG10 CFU/ML CONTENT 7 6 5 4 3 2 1 0 0 5 Lactobacilli 8 Enterobacteriaceae 12 15 DAYS AFTER START Figure 2: Number of Enterobacteriaceae and Lactobacilli in the ileum of piglets after the addition of MCFA to the feed Medium chain fatty acids boosting animal health The latest discovery is that medium chain fatty acids don’t only improve gut health, they also significantly improve the immunity of animals. Numerous research has shown that the viability of neutrophils is reduced enormously under stress conditions. Stress conditions that are frequently occurring in highly productive animals these days: sows around farrowing, piglets around weaning, but also fatteners growing at high growth rates and this not always in optimal conditions. Research showed that medium chain fatty acids significantly increase the neutrophil quality in animals. White blood cells (neutrophils) remain more active making the animal also more resistant against nondigestive disorders. This was also shown at the University of Wageningen, where the use of medium chain fatty acids was the only additive ever tested that gave a significant reduction of the number of veterinary treatments due to lung problems (Table 2). Table 2: Effect of MCFA (Aromabiotic) on veterinary treatments in piglets after weaning (8-20 kg) Negative control AMGP Aromabiotic Significance Amount of pigs 220 220 190 Number of animals treated with antibiotics 26 23 13 n.s. Streptococcus infections 5 2 1 a Pulmonary disorders 7 7 0 * Digestive disorders 5 0 1 a Leg problems 8 12 10 n.s. Others 1 2 1 a Reason of treatment: n.s. = not significant, * = significant, a = numbers too low to test significance Medium chain fatty acids boosting pig performances Because medium chain fatty acids have an antibacterial effect and alter bacterial pathogenicity, they will result in a beneficial microbial ecosystem and thus reduce pathogen-induced intestinal epithelial cell death and an increased villus height. This means less renewal of epithelial villi cells is necessary, meaning a sparing of energy for growth of the animal. An increased villus height is also related to more fully mature enterocytes. Therefore, the increase in villus/crypt ratio that is accomplished by MCFA favors the digestive and absorptive capacities of the small intestine. Also the immunity improving effect means that less energy is needed during inflammation or to renew neutrophils, sparing energy for growth. This is shown in a meta-analyses on the use of Aromabiotic (patented mixture of medium chain fatty acids). The use of Aromabiotic clearly resulted in improved feed conversion ratios in fattening pigs (Figure 2). With animal feed being the biggest part of the production cost in fattening pigs, the impact on economical return is huge. In this meta-analyses, the same positive results were obtained on mortality and growth performances, both in piglets and in fattening pigs. Figure 3: Effect of Aromabiotic-MCFA on FCR of fattening pigs, in 8 negative and 7 positive control trials. In 12 out of 15 trials the medium chain fatty acids improved feed conversion ratio. The use of medium chain fatty acids in sows The use of medium chain fatty acids has also beneficial effects in sows. An improved gut health of the sow will not only result in higher litter sizes, it will also increase lactation feed intake and milk production. Next to this the healthy gut microbiota of the sow can also be ‘transferred’ to the piglets. As the gut of the piglet is sterile at birth, it is quickly colonized by bacteria derived from the sow. When the gut microbiota of the sow is shifted to the beneficial bacteria, the risk for piglets to become infected with E. Coli, S. Suis and Clostridium bacteria is lower. This will reduce the risk for developing neonatal piglet diarrhea and Streptococcus related problems. Furthermore, MCFA’s can increase the energy available for newborn piglets, by increasing the glycogen reserves in piglets. MCFA’s can also exert a bioactive effect on mammary glands and thus increase the colostrum production of sows. These properties reduce the pre-weaning mortality in piglets, while improving their growth performances Conclusion With strongly increasing insights in genetic selection, today’s sows, piglets and fatteners possess an enormous genetic potential which cannot be kept up by standard nutrition. On top of this the reduced use of antibiotics, creates the need for reliable alternatives. It is clear that the broad spectrum activity and mode of actions of medium chain fatty acids make them an ideal solution to reduce antibiotic use. Not only can they reduce the antibiotic use, they even have add-on effects when used together with antibiotics. In this way they can reduce the duration of the antibiotic treatment, and gradually reduce the antibiotic use in time. These medium chain fatty acids are included in patented Nuscience products like Aromabiotic, Salbiotic, VitaGP and in the Nuscience prestarter and starter concepts. References available on request