WO2021160227A1

WO2021160227A1 - Starch propionate to promote growth and/or to obtain a faster weight gain and/or to enhance feed utilization and/or to enhance the development of the gastrointestinal tract used as feed additive or feed ingredient for agricultural animals and aquaculture animals

Info

Publication number: WO2021160227A1
Application number: PCT/DK2020/050407
Authority: WO
Inventors: Ole ABILDGAARD; Theis WILBEK
Original assignee: Abildgaard Ole; Wilbek Theis
Priority date: 2020-02-11
Filing date: 2020-12-27
Publication date: 2021-08-19
Also published as: DK202000169A1; DK180688B1

Abstract

The invention concerns the application of starch propionate as a feed additive and/or ingredient to feed to aquaculture and agricultural animals. It promotes growth and/or obtains a faster weight gainand/or better feed utilization and/or improved meat percentage. Starch propionate functions as a platform for the liberation of propanoic acid in the lower gastrointestinal tract where fermentation of dietary fibers takes place. It passes undigested through the upper part of the gastrointestinal tract.In the colon / lower intestinal tract, propanoic acid is liberated and enhances the concentration of propanoic acid. Propanoic acid stimulates the intestinal wall and promotes the development of the gastrointestinal tract to increase villi length, increase the surface area and increase the cell density. By this more nutrients can be absorbed. In aquaculture and agricultural animals, a healthier gastrointestinal tract will promote growth, and lower the need for antibiotics and medicinal zinc.

Description

Starch propionate to promote growth and/or to obtain a faster weight gain and/or to enhance feed utilization and/or to enhance the development of the gastrointestinal tract used as feed additive or feed ingredient for agricultural animals and aquaculture animals

5DESCRIPTION

Technical field

The invention concerns the application of starch propionate as a feed additive and/or feed ingredient for aquaculture and agricultural animals to promote growth and/or to obtain a faster lOweight gain and/or to ehance the feed utilization. Starch propionate as a feed additive and/or feed ingredient can be applied to increase the utilization of feed i.e. the weight gain to feed ratio, and to improve the gastrointestinal tracts development and size in aquaculture and agricultural animals. Starch propionate is starch esterified with propanoic acid in varying degrees. Starch consists of two different types of polymers, amylose and amylopectin, and can originate from different sources. 15e.g. potatoes, rice, wheat, corn/maize and more. Depending on the source, the relationship between amylose and amylopectin can vary. Amylose is a linear polymer of glucose joined by a-1, 4- glycoside bonds in varying length. Amylopectin is likewise a polymer of glucose joined by a-1, 4- glycoside bonds, but also have branches to other a-1, 4-glycoside chains by a-1, 6-glycoside bonds. The degree of branching can vary, but is often in the range of 5%.

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Background Art

Propanoic acid is one of the three ’short-chain fatty acids’ (SCFAs) that can act as natural sources of energy for animals. The three SCFAs are acetic acid, propanoic acid and butyric acid and are known to have health promoting effects in animals. SCFAs in animals are primarily produced by 25fermentation of dietary fibers by bacteria in the colon. There are several types of dietary fibers but only resistant starches and soluble fibers are fermentable where as e.g. fibres like cellulose do not easily ferment if at all. SCFAs are produced from fermentation and are absorbed by the intestine and in this way SCFAs enters the metabolism as a natural energy source. SCFAs additionally activates different types of receptors found on the cells comprising the intestinal membrane and 30intestinal wall. One of the consequences of this is that peptide hormones, like GLP1, GLP2 and PPY, are released from the endocrine L cells found in the intestinal epithelium /intestinal membrane. Additionally the general health of the intestine is enhanced by the presence of SCFAs, by e.g. increasing the growth of the intestinal epithelium, tightening joints between the cells in the membrane and increasing the number of cells in the intestinal epithelium including the endocrine 35cells and thus also L-cells. Overall it is found that increasing the concentration and availability of SCFAs in the gastrointestinal tract in animals increases the size and weight of the intestinal tract, through the increased proliferation of intestinal cells, thus enhancing its functionality.

Increased concentration and availability of SCFAs in the lumen inside the intestine increases the concentration of the same SCFAs in the bloodstream, and when carried to the liver it’s metabolism 5is influenced in part due to SCFA receptors on the liver cells and the role of propanoic acid in the metabolism.

There is a correlation between presence of SCFAs in the lumen and the amount of “Insulin Like Growth Factor”, IGF-1, released into the bloodstream. IGF-1 is strongly correlated to the growth and development of young animals and is thus one likely reason why increased presence of SCFAs lOin the lumen enhances the growth and development of young animals.

Increased propionic acid in the bloodstream also changes the liver metabolism and promotes the liver to produce glucose and lowers lipid synthesis in the liver and fat tissue with the effect that the animals overall meat to fat ratio also known as meat percentage increases 15

Propanoic acid and butyric acid have a higher degree of health promoting effects than acetic acid, as they are more potent in binding to SCFA receptors. SCFAs can be added directly to the feed however, this will only have a diminished effect , since they are rapidly absorbed in the upper part of the intestinal tract and metabolized. SCFAs absorbed in the upper part of the gastrointestinal 20tract do not interact with receptors and promote intestinal development in the lower part of the gastrointestinal tract. A release of SCFAs in the lower part of the gastrointestinal tract is essential to obtain the effects that its interaction with SCFA-receptors and enhanced cell metabolism promote. This release of SCFAs in the lower gastrointestinal tract is naturally achieved by fermentation of dietary fibers by certain strains of bacteria present in the lower part of the 25gastrointestinal tract,. The presence of SCFAs in the lower part of the gastrointestinal tract in aquaculture animals [1-7] and agricultural animals, like fish, shrimps, poultry, pigs, cows, sheep and more are necessary and essential for a fast and healthy development of their gastrointestinal tracts. To obtain a slow release in the lower gastrointestinal tract different products are sold to aquaculture and agricultural production, which releases SCFAs gradually and in the lower part of 30the gastrointestinal tract due to e.g. encapsulation/coating, incorporation into triglycides or as salts. This slow release has been shown to promote growth, enhance the utilization of feed as well as to enhance the development of the gastrointestinal tract. In pigs the release of SCFAs in the gastrointestinal tract has been shown to promote cell proliferation in the intestinal wall and to reduce apoptosis. This in turn resulted in increased villi length and an increased general health of the gastrointestinal tract with tighter membranes and diminished inflammation. It also showed the overall size of the gastrointestinal tract to increase in length and weight.

The amount and distribution of acetic acid, propanoic acid and butyric acid produced by 5fermentation in the gastrointestinal tract depends on the feed, and on the presence and abundance of the strains of SCFA producing bacteria.

Starch propionate is not metabolized in the upper gastrointestinal tract, because the starch is esterified and therefore becomes a resistant starch. Starch propionate passes un-degraded to the lOlower gastrointestinal tract, where the esters are hydrolyzed through the action of digestive enzymes, in the part of the intestinal tract where natural bacterial fermentation takes place. In this way, propanoic acid is released and increases the amount of propanoic acid in this part the intestinal tract where bacteria naturally supply the organism and metabolism with propanoic acid. The de-esterified starch, after the propanoic acid has been released from the starch, will itself 15subsequently be available for fermentation and like a “normal” fermentable dietary fiber, provide nutrition to the fermenting bacteria, strengthening their presence and producing yet additional SCFA.

The amount of propanoic acid released by de-esterification of starch propionate is significantly 201arger than the amount produced by normal fermentation of dietary fibers in feed. Due to aquaculture animals and agricultural animals typically being treated with medicinal zinc and antibiotics to reduce the risks of infections and enhance growth, the fermenting bacteria present in the lower intestinal tract are reduced in amount and in number of species. This reduced bacterial presence lowers the animals’ ability to produce propanoic acid in the lower gastrointestinal tract.

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By esterification of starch with propanoic acid, the starch propionate acquire properties like resistant starch, allowing it to be carried un-degraded to the lower intestinal tract / the colon where it releases propanoic acid and where the de-esterified starch can be fermented by bacteria. The effect of starch propionate to increase the level of propanoic acid in the colon is very much higher 30than the effect of naturally occurring resistant starch. 30 grams of starch propionate (with e.g. 8% propanoic acid and a water content below 20%) will selectively increase the amount of propanoic acid in the colon by 2 gram and additionally also supply 20 gram of starch for possible fermentation. First, esters are cleaved by enzymes present in the colon and subsequently the resulting starch is fermented by the bacteria in the colon. Because fermentation is limited or inhibited due to unnatural feed and by lack of bacteria in young animals / fish and marine animals, the naturally occurring propanoic acid may be substantially diminished, in which cases this delivery method relieves a serious problem that causes delayed gastrointestinal development with side effects like diminished growth, intestinal inflammation and 5diarrhea.

Disclosure of Invention

The effect of starch propionate, to increase propanoic acid in the lower part of the gastrointestinal tract, is significantly higher than natural fermentation of dietary fibers like resistant starch and thus lOthe application and effect described in claim 1-6 differs from the application and effect of resistant starch due to a higher concentration and availability of propanoic acid in the lower part of the gastrointestinal tract / colon. Thus, this invention is to use starch propionate to deliver propanoic acid to the part of the intestinal tract where natural fermentation takes place, and to obtain the effects described in the claim 1-6. The de-esterification of starch propionate is the major cause of 15increased presence of propanoic acid in the colon and makes it possible for the applications described in claim 1-6. In this way, the main purpose of the esterification of starch with propanoic acid is not to convert the starch to resistant starch and obtain fermentation of the starch in the lower intestinal tract, but to obtain the delivery of propanoic acid directly where fermentation of dietary fibers in the gastrointestinal tract takes place and thus to elevate the level of propanoic acid 20selectively to a greater extend and independently of the natural fermentation, dependent on the bacterial composition. Besides starch propionate being a more effective method to increase the amount of propanoic acid in the gastrointestinal tract compared to resistant starch and other dietary fibers, it also ensures the increase independently of the microbiome composition present in the animals. As explained above the presence of the propionate producing bacteria cannot be taken for 25granted as aquaculture animals and agricultural animals to a large extend have lost the naturally occurring bacterial strains, causing a decreased ability to produce SCFAs including propanoic acid. Thus, the effect of using starch propanoate for delivery of propanoic acid to the colon / lower intestinal tract in aqua culture and agricultural animals is also to overcome this risk and to secure a certain, exact and reproducible method for obtaining this delivery.

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It is commonly known that resistant starch can reduce the use of antibiotics in agricultural animals, but while doing so it may reduce the growth due to reduced intake of degradable starch or other feed, since the resistant starch takes up space in the feed while not to the same extend being digestible and able to supply energy for the metabolism [7]. To avoid this, there are already 35products on the marked that can deliver propanoic acid in the lower part of the gastrointestinal tract independent of bacterial fermentation. An example of a product like this is “Biomin Biotronic top3”, where propanoic acid is incorporated into inorganic phyllo-silicate, which is slowly delivered while dissolving in the intestinal tract thereby delivering propanoic acid in the lower intestine which then promotes growth and improved feed utilization in animals [8]. This product is 5rather expensive and it can be questioned to what extend the propanoic acid is released in parts of the gastrointestinal tract where it has no or little effect. Starch propionate more effectively and selectively can be applied to the same purpose and it can be produced far cheaper. Biomin Biotronic top3 furthermore gives an “off” flavor by addition to feed that has been seen to complicate the application. Starch propionate in contrast has a neutral taste and does not present lOthis problem. Additionally starch propionate has the advantage that it more specifically liberates propanoic acid where fermentation takes place and that bacteria can use the remaining starch for fermentation and in this way on top of an effective, precise and accountable delivery, contributes to the diet as a fermentable dietary fiber. The materials required to produce starch propionate are also cheaper and the production is simpler than production of other products on the marked that 15supports the development of the gastrointestinal tract and reduce that use of antibiotics in agricultural animals.

In conclusion, starch propionate is significantly more effective than alternative products, can be produced and sold cheaper and thus can deliver increased value for the producer of aquaculture animals and agricultural animals.

20Not just the farmers/producers benefit from this application, society benefits due to lower use of feed, making these kind of productions more sustainable. Additionally the animals benefit by overall improvement of health, lower premature death rates, and lower rates of intestinal inflammation, which in aquaculture is a particular concern.

25Brief Description of Drawings

No drawings are included in the application.

Best Mode for Carrying Out the Invention

For the feeding of livestock and poultry, starch propanoate can be added directly in specific doses 30to ready-made feed mixture or sold in a pure powder form to be added and mixed into the feed before delivering to the animals. For aquaculture where fish and marine animals are fed with food mixture pressed into pellets and similar, starch propanoate can be added to the feed mix before pelletizing. The intended estimated usage is an approximate daily dosage for animals of 1,2 grams per kg animal weight /per day of starch propionate with a DS=0,1 and a water content below 20%. It can be evenly mixed into the feed and adapted into the feeding routine of the animals. lndustrial Applicability

Starch propanoate can be used in the agricultural and aquaculture industry and thus fulfills requirements for industrial applicability where this requirement is necessary for patentability.

Mentioned Publications

1. Luckstadt, C. (2009). The use of acidifiers in fish nutrition. Cab Reviews: Perspectives in Agriculture, Veterinary Science, Nutrition and Natural Resources. 3. DOI:

10.1079/P AVSNNR20083044. 2. Hoseinifar, S., Mirvaghefi, A., Amoozegar, M., Merrifield, D. and Ringo, E. (2017), In vitro selection of a synbiotic and in vivo evaluation on intestinal microbiota, performance and physiological response of rainbow trout (Oncorhynchus mykiss) fingerlings. Aquacult Nutr, 23: 111-118. doi:10.1111/anu.l2373 3. LEENHOUWERS, J., PELLIKAAN, W., HUIZING, H., COOLEN, R., VERRETH, J. and SCHRAMA, J. (2008), Fermentability of carbohydrates in an in vitro batch culture method using inocula from Nile tilapia (Oreochromis niloticus) and European sea bass (Dicentrarchus labrax). Aquaculture Nutrition, 14: 523-532. doi:10.1111/j.l365-2095.2007.00558.x 4. Mombach, PI, Adorian, TJ, Pianesso, D, et al. Pectic hydrolysates in the diet of silver catfish (Rhamdia quelen): Growth performance, blood and liver biochemistry, histological parameters and intestinal contents. Aquacult Nutr. 2019; 25: 1378a€“ 1387. https://doi.org/10.llll/anu.12958

5. Ng, W., Lim, C., Romano, N. et al. Dietary short-chain organic acids enhanced resistance tobacterial infection and hepatopancreatic structural integrity of the giant freshwater prawn,

Macrobrachium rosenbergii . Int Aquat Res 9, 293-302 (2017). https://doi.org/10.1007/s40071- 017-0177-y

6. Wee, WC, Mok, CH, Romano, N, Ebrahimi, M, Natrah, I. Dietary supplementation use ofBacillus cereus as quorum sensing degrader and their effects on growth performance and response of Malaysian giant river prawn Macrobrachium rosenbergii juvenile towards Aeromonas hydrophila. Aquacult Nutr. 2018; 24: 1804- 1812.https://doi.org/10.1111/anu.l2819

7. Regassa A, Nyachoti CM. Application of resistant starch in swine and poultry diets with 5particular reference to gut health and function. Anim Nutr. 2018;4(3):305-310. doi:10.1016/j.ani- nu.2018.04.001

8. N. Senkoylu, H. Samli, M. Kanter, et al. Influence of a combination of formic and propionic acids added to wheat- and barley-based diets on the performance and gut histomorphology of lObroiler chickens. Acta Veterinaria Hungarica 200755:4, 479-490.

Claims

1. The use of starch propionate to promote growth and/or to obtain a faster weight gain and/or to improve utilization of feed and/or to enhance the development of the gastrointestinal tract and/

5 or to increase the meat percentage as a feed additive or feed ingredient for agricultural animals and aquaculture animals

2. The use of starch propionate as claimed in claim 1 wherein it increases the utilization of feed.

3. The use of starch propionate as claimed in claim 1 wherein it promotes the development of the gastrointestinal tract.

104. The use of starch propionate as claimed in claim 1 wherein the short chain fatty acid esterified to starch can be any combination and ratio of the three SCFA’s: acetic acid, propanoic acid and butyric acid.

5. The use of starch propionate as claimed in claim 1 wherein it increases the meat percentage.