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[0012]In view of the economical interest of modern animal husbandry systems to increase productivity and maintain profitability, it has become general practice to increase the growth rate by subjecting specific animals (such as piglets,....) to an early weaning. This early weaning however burdens the animal with a lot of adverse stresses, mainly of nutritional origin (Zijlstra et al., 1996). The adverse stresses are often accompanied by a more or less severe decrease in feed intake and energy deficiency and thus involve mobilization of body reserves by the animal. Maldigestion and malabsorption may further aggravate the situation and result in digestive upsets mainly due to bacterial and fungal overgrowth in and/or viral infections of the gastrointestinal tract (Eckel, 1999).
[0013]There is a general belief that the digestive pathology of early weaned animals is mainly caused by Gram negative bacteria, in particular Escherichia coli spp. and Salmonella spp., which are often present in the intestine of the animal as such or may enter the gastrointestinal tract through the feed (Guillot, 1989). To overcome the problem of digestive pathology, which often involves a severe weight loss and an increased mortality amongst the animals, it became common practice to supplement the animal feed with low doses of pharmaceutical antimicrobial substances (for example antibiotics) or therapeutic doses of antibiotics, designated as "antibiotics" further on (Dupont and Steele, 1987; Prescott, 1997). Nowadays however, there is a growing concern on the addition of antibiotics to the feed (Guillot, 1989; Barton, 1998). There is a fear for the risk of the emergence of last-resort antibiotics used in human medicine, of the development of a resistance towards the antibiotics, which would involve a need to increase their dosing or to develop new, stronger antibiotics. There is also a fear that a resistance may emerge amongst living beings after consuming animals that have been treated with those antibiotics. The present concern of environmental disturbance by chemicals and the fact that most of those antibiotics have already been banned in the European Union, or will be in the near future, justify the need
for alternatives, functional as antimicrobial agents (Muirhead, 1998; Ross, 1999).
[0014]As can be derived from the given examples, there is thus a need to find new antimicrobial agents as a substitute for the known antimicrobial agents and for in the mean time sometimes banned antibiotics to overcome microbial (out) growth and to overcome digestive pathology exhibited by animals.
[0015]A further object is to provide an antimicrobial feed additive able to be active at low pH values present in the stomach. This avoids further transit of ingested pathogens to the intestines.
[0016]In this context, specific medium-chain fatty acids MCFA (C6, C7, C8, C9 and C10) are a valuable alternative, since they can be used as novel and innovative antimicrobial agents, in order to control microbial contamination and growth and subsequent toxin production in the gastrointestinal tract and more in particular in the stomach.
[0017]EP-A1-0 089 376 describes a feed additive or feed of accelerating growth of animals containing at least a fatty acid salt or at least a fatty acid salt and a fatty acid ester of sugar. In said document fatty acids consist of about 6-24 carbons and describes a very broad field of chain lengths. No specific sub-range is provided showing a better effect than the broad range.
[0018]EP-A1-0 519 458 describes a feed additive for livestock and a feed for livestock which comprises (a) a triglyceride of a medium-chain fatty acid having 6 to 12 carbon atoms and (b) at least one substance selected from the medium-chain fatty acid[s] having 6 to 12 carbon atoms, a monoglyceride of the [a] fatty acid and a diglyceride of a fatty acid. This composition discloses a combination of fatty acids.
[0019]The main object of the present invention is to provide a more specific and more active range of medium-chain fatty acids having improved antimicrobial, in particular combined antibacterial and antifungal properties. It is believed that said specific combination of activities results surprisingly in an effective feed additive resulting in a[n] improved feed conversion ratio (being the weight feed consumed per kg body weight gain).
[0020]The invention provides therefor the use of two C6-C10 medium-chain fatty acids, emulsions or mixtures thereof for inhibition of microbial contamination, growth and subsequent toxin production. Preferably substantially equal amounts of C8 and C10 are used.
[0021]The present invention describes the use of two medium chain fatty acids (MCFA), chosen from the group consisting of caprylic (C8) acid and capric (C10) acid, mixtures thereof, about equal amounts by weight, in an amount of: 20-50% C8, 20-50% C10 and optionally other MCFA chosen from C6-C24 for the inhibition of microbial contamination, growth and/or the subsequent toxin production.
[0022]The invention relates to the use of two medium chain fatty acids (MCFA), chosen from the group consisting of caprylic (C8) acid and capric (C10) acid, emulsions or mixtures thereof, about equal amounts by weight, in an amount of:
20-50% C8
20-50% C10
and optionally other MCFA chosen from C6- C24
wherein the MCFA concentration is 100-3000ppm for the manufacture of a medicament for the inhibition of microbial contamination, growth and/or the subsequent toxin production.
[0023]The invention further relates to the use as described above, of caprylic (C8) acid and capric (C10) acid in about equal amounts by weight and in a concentration of 100-3000ppm for the manufacture of a medicament for the inhibition of microbial contamination, growth and/or the subsequent toxin production.
[0024]The invention further relates to the use as described above, in combination with other MCFA, such as lauric (C12) and myristic (C14) acid, other antifungal agents or with other (organic) (fatty) acids or with additives, such as aroma’s and plant extracts.
[0025]The invention further relates to the use as described above, for combatting the growth of fungi and yeasts chosen from the group: Penicillium, Aspergillus, Fusarium, Cephalosporum, Saccharomyces, Candida as well as to other Fungi Imperfecti and Hemiascomycetes (yeasts).
[0026]The invention further relates to the use as described above for selective combatting the growth of Gram negative bacteria such as Escherichia coli, Salmonella sp., Shigella sp. and other Gram negative and coliform bacteria and food/feed spoilers.
[0027]The invention further relates to the use as described above for the selective control and regulation of the microbial ecosystem in the gastrointestinal tract of any animal or human.
[0028]The invention further relates to the use as described above wherein the animals are in their early weaning phase.
[0029]The invention also relates to a feed composition for an animal comprising a feed supplement containing one or more medium chain fatty acids (MCFA) chosen from the group consisting of caprylic (C8) acid and capric (C10) acid, emulsions or mixtures thereof in an amount by weight % of:
20-50% C8
20-50% C10
and optionally other MCFA chosen from C6-C24,
wherein the MCFA concentration is 100-3000ppm.
[0030]The invention further relates to a feed composition as described above, containing caprylic (C8) acid and capric (C10) acid in about equal amounts by weight and in a concentration of 100-3000ppm.
[0031]In first instance, the present invention relates to the surprising observation that supplying specific MCFA in the range of C6-C10, or mixtures as a solution or an emulsion thereof to fungi, yeasts and bacteria, inhibit their further growth. Growth of fungi, yeasts and bacteria is inhibited and the respective micro-organisms are killed by the administered MCFA. In the present invention, preferably use is made of a mixture of specific different fatty acids, the individual fatty acids containing a different number of carbon atoms. The inventors have found that such a mixture shows optimal antimicrobial properties. The fatty acids that can be used in this invention include both fatty acids with an even and an odd number of carbon atoms, for example C6 (caproic acid, hexanoic acid), C7 (heptanoic acid), C8 (caprylic acid, octanoic acid), C9 (nonanoic or pelargonic acid) and C10 (capric acid, decanoic acid).
[0032]The antimicrobial effects of fatty acids and their soaps have already been known for a long time and have been reviewed by J.J. Kabara (1978) in "The pharmacological effects of lipids". In this review it is discussed that in homologous series of fatty acids, the bactericidal efficiency has been found to increase with increasing chain length. E. coil spp. And Shigella spp. appear to be killed by moderate concentrations of saturated soaps of lauric acid containing 12 carbon atoms, and stearyl fatty acid containing 18 carbon atoms. Fatty acids with a chain length of 10 to 12 carbon atoms appear to show optimal antimicrobial activity, whereas lower fatty acids with 4-10 carbon atoms appear to have no or little germicidal effect.
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[0034]There is however no teaching in Kabara (1978) that fatty acids containing 8-10 carbon atoms would be capable of controlling the bacterial [growth].
[0035]This particular antimicrobial action of C8-C10 MCFA is in particular effective for a combined inhibition against fungi, yeasts and Gram negative bacteria. Fungi can include following genera: Aspergillus, Candida, Cephalosporum, Fusarium, Penicillium as well as other fungi belonging to the Fungi Imperfecti. Yeasts can include, Saccharomyces and other hemiascomycetes (yeasts). Gram negative bacteria include Escherichia coli, Salmonella sp., Shigella sp. A[a]nd other Gram negative and coliform bacteria and spoilers. By inhibition of growth and by killing the microbial cell, the respective micro-organisms are not able anymore to cause cell intrinsic diseases and to produce further toxins.
[0036]From these results and observations by others in the field, it would be expected that other MCFA are also useful for this application. Other MCFA can include lauric acid (C12) and myristic acid (C14). A concentration up to about 100000 ppm MCFA eventually combined with other (organic) (fatty) acids, antimicrobial agents and additives, such as aroma’s, ..., can be used to achieve this particular goal. 1200 ppm of a mixture of MCFA has been found to be particularly suitable (see examples).
[0037]Conclusive, MCFA (mixtures or emulsions thereof) inhibit microbial growth by killing the microbial cells.
[0038]The invention relates in particular to a specific small range of MCFA (C8-C9-C10) and more in particular about equal amounts in weight of C8 and C10 are suitable as antimicrobial agents. As a result, microbial growth during contamination, during biofouling, during fermentation, in ecological systems such as the gastrointestinal tract can be controlled in a more friendly way, compared to the use of traditional antibiotics such as propionic acid, growth promoters and antibiotics.
[0039]The observed effect is obtained, with the free MCFA or as an emulsion of the MCFA.
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[0042]Hereunder several examples will prove the effectiveness of the antimicrobial effectiveness of MCFA being a 50/50 by weight mixture of C8 and C10. It is clear that these examples will have an explanatory goal and are not limitative to the scope of the invention which is worded in the claims.