WO2024115111A1 - A composition for modulating growth of microorganisms - Google Patents
A composition for modulating growth of microorganisms Download PDFInfo
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- WO2024115111A1 WO2024115111A1 PCT/EP2023/081899 EP2023081899W WO2024115111A1 WO 2024115111 A1 WO2024115111 A1 WO 2024115111A1 EP 2023081899 W EP2023081899 W EP 2023081899W WO 2024115111 A1 WO2024115111 A1 WO 2024115111A1
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- Prior art keywords
- acid
- composition
- microorganisms
- salt
- growth
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- 239000006041 probiotic Substances 0.000 description 5
- 230000000529 probiotic effect Effects 0.000 description 5
- 235000018291 probiotics Nutrition 0.000 description 5
- 239000002535 acidifier Substances 0.000 description 4
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 4
- 235000010235 potassium benzoate Nutrition 0.000 description 4
- 239000004300 potassium benzoate Substances 0.000 description 4
- 229940103091 potassium benzoate Drugs 0.000 description 4
- 235000011044 succinic acid Nutrition 0.000 description 4
- 210000004534 cecum Anatomy 0.000 description 3
- 210000001198 duodenum Anatomy 0.000 description 3
- 230000007613 environmental effect Effects 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 210000001630 jejunum Anatomy 0.000 description 3
- 210000002429 large intestine Anatomy 0.000 description 3
- 229940099690 malic acid Drugs 0.000 description 3
- 239000004460 silage Substances 0.000 description 3
- 210000002784 stomach Anatomy 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- 241000238557 Decapoda Species 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 241001222923 Lactobacillus reuteri F275 Species 0.000 description 2
- 241000282849 Ruminantia Species 0.000 description 2
- 241000607361 Salmonella enterica subsp. enterica Species 0.000 description 2
- 239000003674 animal food additive Substances 0.000 description 2
- 230000000845 anti-microbial effect Effects 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 210000003608 fece Anatomy 0.000 description 2
- 235000021050 feed intake Nutrition 0.000 description 2
- 229960002446 octanoic acid Drugs 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 235000013406 prebiotics Nutrition 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 235000019786 weight gain Nutrition 0.000 description 2
- 230000004584 weight gain Effects 0.000 description 2
- BJEPYKJPYRNKOW-UWTATZPHSA-N (R)-malic acid Chemical compound OC(=O)[C@H](O)CC(O)=O BJEPYKJPYRNKOW-UWTATZPHSA-N 0.000 description 1
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
- 244000303258 Annona diversifolia Species 0.000 description 1
- 235000002198 Annona diversifolia Nutrition 0.000 description 1
- 241001622847 Buttiauxella Species 0.000 description 1
- CBOCVOKPQGJKKJ-UHFFFAOYSA-L Calcium formate Chemical compound [Ca+2].[O-]C=O.[O-]C=O CBOCVOKPQGJKKJ-UHFFFAOYSA-L 0.000 description 1
- BCZXFFBUYPCTSJ-UHFFFAOYSA-L Calcium propionate Chemical compound [Ca+2].CCC([O-])=O.CCC([O-])=O BCZXFFBUYPCTSJ-UHFFFAOYSA-L 0.000 description 1
- 241000282836 Camelus dromedarius Species 0.000 description 1
- 239000005632 Capric acid (CAS 334-48-5) Substances 0.000 description 1
- 239000005635 Caprylic acid (CAS 124-07-2) Substances 0.000 description 1
- 241000282994 Cervidae Species 0.000 description 1
- 241000238424 Crustacea Species 0.000 description 1
- 208000019331 Foodborne disease Diseases 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- 241000289581 Macropus sp. Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 239000004280 Sodium formate Substances 0.000 description 1
- 239000004283 Sodium sorbate Substances 0.000 description 1
- 108010073771 Soybean Proteins Proteins 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000001668 ameliorated effect Effects 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- XJMWHXZUIGHOBA-UHFFFAOYSA-N azane;propanoic acid Chemical compound N.CCC(O)=O XJMWHXZUIGHOBA-UHFFFAOYSA-N 0.000 description 1
- 235000013405 beer Nutrition 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 description 1
- 235000011092 calcium acetate Nutrition 0.000 description 1
- 239000001639 calcium acetate Substances 0.000 description 1
- 229960005147 calcium acetate Drugs 0.000 description 1
- FNAQSUUGMSOBHW-UHFFFAOYSA-H calcium citrate Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O FNAQSUUGMSOBHW-UHFFFAOYSA-H 0.000 description 1
- 239000001354 calcium citrate Substances 0.000 description 1
- 229960004256 calcium citrate Drugs 0.000 description 1
- 239000004281 calcium formate Substances 0.000 description 1
- 235000019255 calcium formate Nutrition 0.000 description 1
- 229940044172 calcium formate Drugs 0.000 description 1
- MKJXYGKVIBWPFZ-UHFFFAOYSA-L calcium lactate Chemical compound [Ca+2].CC(O)C([O-])=O.CC(O)C([O-])=O MKJXYGKVIBWPFZ-UHFFFAOYSA-L 0.000 description 1
- 239000001527 calcium lactate Substances 0.000 description 1
- 235000011086 calcium lactate Nutrition 0.000 description 1
- 229960002401 calcium lactate Drugs 0.000 description 1
- 235000010331 calcium propionate Nutrition 0.000 description 1
- 239000004330 calcium propionate Substances 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000013351 cheese Nutrition 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000001723 curing Methods 0.000 description 1
- 235000021051 daily weight gain Nutrition 0.000 description 1
- 150000001990 dicarboxylic acid derivatives Chemical class 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- OPGYRRGJRBEUFK-UHFFFAOYSA-L disodium;diacetate Chemical compound [Na+].[Na+].CC([O-])=O.CC([O-])=O OPGYRRGJRBEUFK-UHFFFAOYSA-L 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 235000012041 food component Nutrition 0.000 description 1
- 239000005428 food component Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229940116298 l- malic acid Drugs 0.000 description 1
- 238000009630 liquid culture Methods 0.000 description 1
- 239000011738 major mineral Substances 0.000 description 1
- 235000011963 major mineral Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000001471 micro-filtration Methods 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 150000002829 nitrogen Chemical class 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 235000021232 nutrient availability Nutrition 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 238000005554 pickling Methods 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 235000020777 polyunsaturated fatty acids Nutrition 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 239000001508 potassium citrate Substances 0.000 description 1
- 229960002635 potassium citrate Drugs 0.000 description 1
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 description 1
- 235000011082 potassium citrates Nutrition 0.000 description 1
- 235000010241 potassium sorbate Nutrition 0.000 description 1
- 239000004302 potassium sorbate Substances 0.000 description 1
- 229940069338 potassium sorbate Drugs 0.000 description 1
- BINNZIDCJWQYOH-UHFFFAOYSA-M potassium;formic acid;formate Chemical compound [K+].OC=O.[O-]C=O BINNZIDCJWQYOH-UHFFFAOYSA-M 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000009938 salting Methods 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 229940083542 sodium Drugs 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- MFBOGIVSZKQAPD-UHFFFAOYSA-M sodium butyrate Chemical compound [Na+].CCCC([O-])=O MFBOGIVSZKQAPD-UHFFFAOYSA-M 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 229960001790 sodium citrate Drugs 0.000 description 1
- 235000011083 sodium citrates Nutrition 0.000 description 1
- 235000017454 sodium diacetate Nutrition 0.000 description 1
- HLBBKKJFGFRGMU-UHFFFAOYSA-M sodium formate Chemical compound [Na+].[O-]C=O HLBBKKJFGFRGMU-UHFFFAOYSA-M 0.000 description 1
- 235000019254 sodium formate Nutrition 0.000 description 1
- JXKPEJDQGNYQSM-UHFFFAOYSA-M sodium propionate Chemical compound [Na+].CCC([O-])=O JXKPEJDQGNYQSM-UHFFFAOYSA-M 0.000 description 1
- 235000010334 sodium propionate Nutrition 0.000 description 1
- 239000004324 sodium propionate Substances 0.000 description 1
- 229960003212 sodium propionate Drugs 0.000 description 1
- LROWVYNUWKVTCU-STWYSWDKSA-M sodium sorbate Chemical compound [Na+].C\C=C\C=C\C([O-])=O LROWVYNUWKVTCU-STWYSWDKSA-M 0.000 description 1
- 235000019250 sodium sorbate Nutrition 0.000 description 1
- 229940001941 soy protein Drugs 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000010902 straw Substances 0.000 description 1
- 238000009923 sugaring Methods 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- UAXOELSVPTZZQG-UHFFFAOYSA-N tiglic acid Natural products CC(C)=C(C)C(O)=O UAXOELSVPTZZQG-UHFFFAOYSA-N 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- 235000013337 tricalcium citrate Nutrition 0.000 description 1
- 230000004222 uncontrolled growth Effects 0.000 description 1
- 238000011514 vinification Methods 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 235000013618 yogurt Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/105—Aliphatic or alicyclic compounds
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/111—Aromatic compounds
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/158—Fatty acids; Fats; Products containing oils or fats
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K30/00—Processes specially adapted for preservation of materials in order to produce animal feeding-stuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K50/00—Feeding-stuffs specially adapted for particular animals
- A23K50/10—Feeding-stuffs specially adapted for particular animals for ruminants
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K50/00—Feeding-stuffs specially adapted for particular animals
- A23K50/20—Feeding-stuffs specially adapted for particular animals for horses
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K50/00—Feeding-stuffs specially adapted for particular animals
- A23K50/30—Feeding-stuffs specially adapted for particular animals for swines
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K50/00—Feeding-stuffs specially adapted for particular animals
- A23K50/60—Feeding-stuffs specially adapted for particular animals for weanlings
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K50/00—Feeding-stuffs specially adapted for particular animals
- A23K50/70—Feeding-stuffs specially adapted for particular animals for birds
- A23K50/75—Feeding-stuffs specially adapted for particular animals for birds for poultry
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L3/00—Preservation of foods or foodstuffs, in general, e.g. pasteurising, sterilising, specially adapted for foods or foodstuffs
- A23L3/34—Preservation of foods or foodstuffs, in general, e.g. pasteurising, sterilising, specially adapted for foods or foodstuffs by treatment with chemicals
- A23L3/3454—Preservation of foods or foodstuffs, in general, e.g. pasteurising, sterilising, specially adapted for foods or foodstuffs by treatment with chemicals in the form of liquids or solids
- A23L3/3463—Organic compounds; Microorganisms; Enzymes
- A23L3/3481—Organic compounds containing oxygen
- A23L3/3508—Organic compounds containing oxygen containing carboxyl groups
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Definitions
- a composition for modulating growth of microorganisms A composition for modulating growth of microorganisms
- the present invention relates to a composition for modulating growth of microorganisms and use thereof.
- microorganisms It is well known in the field of microbiology that the growth behavior of microorganisms depends on environmental conditions. Certain conditions may favor microbial growth while other conditions may reduce growth. Notably, certain environmental conditions may result in a growth reduction or even growth stagnation of some microorganisms, whereas other microorganisms may not be affected at all or may even show increased growth upon exposure to the same conditions.
- temperature conditions may be chosen to disfavor microbial growth.
- products subjected to a risk of microbial spoilage may be kept frozen or at least may be stored at low temperatures, e.g. below 10 °C.
- Further options to modulate or control microbial growth include the removal of water e.g. by lyophilization, smoking, salting, curing, sugaring or pickling. In some preservation processes, an acidic pH environment is established to disfavor the growth of unfavorable and potentially pathogenic microorganisms.
- acidifier products including organic acids may be used to maintain food and feed hygiene and prevent spoilage by microorganisms such as bacteria or molds.
- Organic acids e.g. formic acid, propionic acid or acetic acid as described in EP 2 642 874 may be used to control microbial growth in foodstuff, food or feed with the aim to minimize the risk for foodborne diseases.
- acidifier products may be added pre- and/or post-production of finished feed.
- acidifier products may be used to achieve a reduced growth of potentially pathogenic microorganisms in the gastrointestinal tract, but also to improve feed conversion rate and weight gain upon ingestion.
- benzoic acid and/or at least one salt thereof in combination with at least one additional organic acid and/or at least one salt thereof, provides enhanced antimicrobial effect.
- the present invention provides a composition for modulating growth of microorganisms, comprising a) benzoic acid and/or at least one salt thereof, and b) at least one additional organic acid and/or at least one salt thereof.
- the present invention also provides use of the above composition for modulating growth of microorganisms, and a method by using the composition for modulating growth of microorganisms.
- the present invention further provides use of at least one additional organic acid and/or at least one salt thereof in the composition as defined herein for boosting the effect of benzoic acid and/or at least one salt thereof in modulating growth of microorganisms.
- the present invention provides a composition for modulating growth of microorganisms, wherein the composition comprises a) benzoic acid and/or at least one salt thereof, and b) at least one additional organic acid and/or at least one salt thereof.
- the at least one salt of benzoic acid may be selected from the group consisting of sodium benzoate, magnesium benzoate, manganese benzoate, potassium hypophosphite, aluminium benzoate, calcium benzoate and ferric benzoate, preferably sodium benzoate, magnesium benzoate, manganese benzoate and potassium benzoate, and more preferably sodium benzoate.
- the at least one additional organic acid is any organic acid other than benzoic acid, which may be selected from the group consisting of short monocarboxylic acids having between 1 and 6 carbon atom(s), saturated dicarboxylic acids, unsaturated dicarboxylic acids, unsaturated carboxylic acids, saturated carboxylic acids, hydroxycarboxylic acids, aromatic carboxylic acids, and/or keto carboxylic acids.
- examples of the short monocarboxylic acids having between 1 and 6 carbon atom(s) are formic acid, acetic acid, propionic acid, butyric acid, isobutyric acid, 3-methylbutyric acid, 2-methylbutyric acid, 2-ethylbutyric acid, valeric acid and hexanoic acid.
- Examples of the saturated dicarboxylic acids are adipic acid and succinic acid.
- An example of the unsaturated dicarboxylic acid is fumaric acid.
- examples of the unsaturated carboxylic acids are sorbic acid and oleic acid.
- Examples of the saturated carboxylic acids are stearic acid, octanoic acid (also referred to as caprylic acid), decanoic acid (also referred to as capric acid) and dodecanoic acid (also referred to as lauric acid).
- Examples of the hydroxycarboxylic acids are lactic acid, malic acid (D-, or L-, or D/L-malic acid), citric acid and tartaric acid.
- An example of the aromatic carboxylic acids is cinnamic acid.
- An example of the keto carboxylic acid is pyruvic acid.
- the at least one additional organic acid is selected from the group consisting of formic acid, acetic acid, propionic acid, butyric acid, isobutyric acid, 3-methylbutyric acid, 2-metylbutyric acid, 2-ethylbutyric acid, valeric acid, hexanoic acid, adipic acid, succinic acid, fumaric acid, sorbic acid, oleic acid, stearic acid, octanoic (caprylic) acid, decanoic (capric) acid, dodecanoic (lauric) acid, lactic acid, malic acid, citric acid, tartaric acid, cinnamic acid, pyruvic acid, gluconic acid, suberic acid, malonic acid, tannic acid, caffeic acid, ellagic acid, perillic acid and gallic acid.
- formic acid acetic acid, propionic acid, butyric acid, isobutyric acid, 3-methylbutyric acid
- the at least one additional organic acid is selected from formic acid, acetic acid, propionic acid, butyric acid, isobutyric acid, 3-methylbutyric acid, 2-metylbutyric acid, 2-ethylbutyric acid, valeric acid, hexanoic acid, adipic acid, succinic acid, fumaric acid, sorbic acid, oleic acid, stearic acid, octanoic (caprylic) acid, decanoic (capric) acid, dodecanoic (lauric) acid, lactic acid, malic acid, citric acid, tartaric acid, cinnamic acid and pyruvic acid, or at least one salt thereof.
- the at least one additional organic acid is selected from formic acid, acetic acid, propionic acid, fumaric acid and succinic acid.
- the most preferably, the at least one additional organic acid is selected from fumaric acid and succinic acid.
- the at least one salt of the additional organic acid may be any one of metal salts such as potassium, sodium or calcium salts, and ammonium salts.
- the salts of the organic acid include but are not limited to ammonium formate, potassium diformate, sodium diacetate, calcium acetate, ammonium propionate, sodium propionate, calcium propionate, calcium lactate, potassium sorbate, sodium formate, calcium formate, sodium butyrate, sodium sorbate, potassium citrate, sodium citrate and calcium citrate.
- the composition according to the invention may comprise benzoic acid and/or at least one salt thereof in combination with more than one additional organic acid and/or at least one salt thereof.
- such a composition may comprise benzoic acid and/or at least one salt thereof in combination with two, three, four, five or even more additional organic acids.
- the composition comprises benzoic acid and/or a salt of benzoic acid and at least three additional organic acids, especially formic acid, acetic acid and propionic acid, wherein the salt of benzoic acid is selected from the group consisting of sodium benzoate, manganese benzoate, magnesium benzoate and potassium benzoate, preferably sodium benzoate or manganese benzoate, more preferably sodium benzoate.
- the composition according to the invention comprises benzoic acid and/or a salt of benzoic acid and at least four additional organic acids, especially formic acid, acetic acid, propionic acid and fumaric acid, wherein the salt of benzoic acid is selected from the group consisting of sodium benzoate, manganese benzoate, magnesium benzoate and potassium benzoate, preferably sodium benzoate or manganese benzoate, more preferably sodium benzoate.
- the composition according to the invention comprises benzoic acid and/or a salt of benzoic acid and at least five additional organic acids, especially formic acid, acetic acid, propionic acid, fumaric acid and succinic acid, wherein the salt of benzoic acid is selected from the group consisting of sodium benzoate, manganese benzoate, magnesium benzoate and potassium benzoate, preferably sodium benzoate or manganese benzoate, more preferably sodium benzoate.
- composition of the present application may be formulated in the form of a feed additive (premix) or a food additive or a feed or a food for administering to animals.
- a composition may further comprise components, such as one or more of the following: Fat- or water-soluble vitamin(s), trace- and/or macro-mineral(s), (proteinogenic) amino acid(s), organic and/or inorganic adsorbant(s), polyunsaturated fatty acid(s), antimicrobial polypeptide(s), pre- and/or pro-biotic(s), flavoring and/or coloring agent(s), microorganism(s) and/or enzyme(s) to facilitate better nutrient availability and/or to mitigate undesired effects) of feed/food contaminants).
- compositions according to the invention may be provided in a form wherein one or more or all of the components is/are provided in solid form (e.g. salt, powder, granulate, pellet etc.) or in liquid form (e.g. aqueous, gel, viscous). It is also considered that the composition may be provided in a manner, wherein one component (e.g. one or more organic acid(s)) is provided in liquid form and a second component is provided in solid form (e.g. benzoic acid), and the composition is formed by combining the two components in a mixture or in a separate form.
- solid form e.g. salt, powder, granulate, pellet etc.
- liquid form e.g. aqueous, gel, viscous
- one component e.g. one or more organic acid(s)
- a second component is provided in solid form (e.g. benzoic acid)
- said composition may be provided in a particular manner, wherein the molar ratio of the at least one additional organic acid and/or the at least one salt thereof to benzoic acid and/or the at least one salt thereof is from 0.001 :1 to 500:1 , preferably from 0.005:1 to 300:1 , more preferably from 0.01 :1 to 200:1 , such as from 0.01 :1 to 0.15:1 , from 0.02:1 to 0.1 :1 , from 0.04:1 to 100:1 , from 0.05:1 to 100:1 , , from 0.1 :1 to 100:1 , from 1 :1 to 100:1 , from 10:1 to 80:1 and from 20:1 to 40:1.
- the at least one additional organic acid and/or the at least one salt thereof may be provided at any concentration from 0.2 mmol to 100 mmol such as 0.2. 0.4, 0.8. 1.5, 3.1 , 6.25, 12.5, 25.0, 50.0 and 100 mmol, in combination with benzoic acid and/or at least one salt thereof at any concentration from 0.2 mmol to 20 mmol such as 0.3, 0.6, 1 .3, 2.5, 5.0, 10 and 20 mmol, per 1 Kg of the composition in solid form or per 1 L of the composition in liquid form.
- the molar ratio of the at least one additional organic acid and/or the at least one salt thereof to benzoic acid and/or the at least one salt thereof is in the range of from 0.001 :1 to 0.15:1.
- composition of the present invention can be used for modulating growth of microorganisms, i.e., inhibiting the growth of pathogenic microorganisms and/or enhancing the growth of beneficial (i.e. probiotic) microorganisms.
- the microorganisms may be any one or more of the genera of Butiauxella, Citrobacter, Cronobacter, Enterobacter, Escherichia, Edwardsiella, Klebsiella, Phytobacter, Plesiomonas, Pseudoescherichia, Raoultella, Salmonella, Shigella, Proteus, Yersinia, Vibrio, Aeromonas, Clostridium, Pseudomonas, Staphylococcus, Pasteurella, Brachyspira, Campylobacter, Listeria, Streptococcus, Haemophilus, Brucella, Moritella, Tenacibaculum, Lactobacillus, Bifidobacterium, Saccharomyces, Bacillus, Pediococcus, Enterococcus, Streptococcus, Propionibacterium, Pseudomonas and Citrobacter.
- the microorganisms in the present invention may be any one or more of Escherichia coll, Salmonella enterica, Shigella sonnei, Clostridium perfringens, Lactobacillus reuteri, Enterococcus faecium and Bacillus subtilis.
- the pathogenic microorganisms in the present invention may be at least one of the genera of Buttiauxella, Citrobacter, Cronobacter, Enterobacter, Escherichia, Edwardsiella, Klebsiella, Phytobacter, Plesiomonas, Pseudoescherichia, Raoultella, Salmonella, Shigella, Proteus, Yersinia, Vibrio, Aeromonas, Clostridium, Pseudomonas, Staphylococcus, Pasteurella, Brachyspira, Campylobacter, Listeria, Streptococcus, Haemophilus, Brucella, Moritella and Tenacibaculum, in particular may be selected from the group consisting of Escherichia coli, Salmonella enterica, Shigella sonnei and Clostridium perfringens.
- the beneficial microorganisms in the present invention may be at least one microorganism selected from the genera of Lactobacillus, Bifidobacterium, Saccharomyces, Bacillus, Pediococcus, Enterococcus, Streptococcus, Propionibacterium, Pseudomonas and Citrobacter, in particular may be selected from the group consisting of Lactobacillus reuteri, Enterococcus faecium and Bacillus subtilis.
- the composition of the present invention was capable of modulating growth of microorganisms in a synergistic model.
- the term “in a synergistic model” means that, in a test of modulating growth of microorganisms, for example, according to the example 1 of the present invention, the composition of the present invention provides observed value (“O”) beyond the expected value (“E”) resulting from the individual ingredient of the composition, i.e, benzoic acid and/or salt thereof and the additional organic acid and/or salt thereof.
- the expected value (“E”) can be calculated according to the formula developed by Colby etal. (1967. Weeds 15(1): 20-22), which is incorporated herein as reference.
- the expression “observed value (“O”) beyond the expected value (“E”)” means that the result of the observed value minus the expected value, i.e., E - O, is bigger than zero (0), preferably no less than 1 , 2, 3, 5, 8 10, and more preferably no less than 10.
- the present invention also provides a composition as described above, wherein in a test of modulating growth of microorganisms the composition of the present invention provides observed value (“O”) beyond the expected value (“E”) resulting from the individual ingredient of the composition, i.e, benzoic acid and/or salt thereof and the additional organic acid and/or salt thereof.
- the composition may comprise benzoic acid and/or at least one salt thereof and the at least one additional organic acid and/or at least one salt thereof as the only active ingredients for modulating growth of microorganisms.
- the composition of the present invention besides benzoic acid and/or at least one salt thereof and the at least one additional organic acid and/or at least one salt thereof, may comprises additional active ingredients such as enzymes for modulating growth of microorganisms.
- the present invention provides use of the composition as described herein for modulating growth of microorganisms, i.e., inhibiting the growth of pathogenic microorganisms and/or enhancing the growth of beneficial (i.e. probiotic) microorganisms.
- the microorganisms may be present in a food and /or a feed, and/or in the gastrointestinal tracts of animals.
- the present invention provides use of the composition as described herein for modulating growth of microorganisms, especially for inhibiting the growth of pathogenic microorganisms, in a food and/or a feed.
- the present invention provides use of the composition as described herein for modulating growth of microorganisms in the gastrointestinal tract, especially in the intestinal tracts (e.g. stomach, duodenum, jejunum, illeum, cecum, and/or large intestine) of animals.
- the present invention provides use of the composition as described herein for improving gut health of animals.
- the present invention provides use of the composition as described herein for the treatment, amelioration and/or prevention of post-weaning diarrhea (PWD) of animals, such as pigs.
- PWD post-weaning diarrhea
- animals such as pigs.
- PWD is often caused by strains of Escherichia coll in the gastrointestinal tract of animals (e.g. Fairbrother et al. 2005. Anim Health Res Rev. 6(1):17-39), resulting in considerable economic loss and animal malady.
- growth of such strains can be reduced in the gastrointestinal tract of animals (e.g. pigs) by administering to the animals the composition described herein, and thereby PWD can be treated, ameliorated and/or prevented.
- the treatment, amelioration and/or prevention of PWD can be characterized by for example increased faeces score.
- the faeces score is increased by at least 1%, 2%, 3%, 5%, 10% or more.
- the present invention provides use of the composition as described herein for improving growth performance of animals.
- one or more of the characters of growth performance such as weight gain, daily weight gain, feed intake, daily feed intake, feed conversion ratio and/or mortality ratio of animals could be improved because of the effect of the composition as described herein in modulating growth of microorganisms in the gastrointestinal tract of animals.
- any of the characters of growth performance is improved by at least 1 %, 2%, 3%, 5%, 10%, 15%, 20% or more because of the composition as described herein.
- the terms “food” and “feed” are used to refer to any component, ingredient, preparation, mixture or additive suitable for, or intended for oral intake by animals.
- the food and/or the feed include but are not limited to foodstuff; fodder; feed; silage; foodstuff additive; fodder additive; feed additive; silage additive; feed or food components such as crop, grain such as wet distillers grain and dried distillers grain, hay, straw, protein sources such as soy protein, starch and carbohydrates etc.; nutritional supplement; prebiotic; probiotic; intermed iate/s thereof; and/or mixture/s thereof.
- the term “animal” or “animals” refers to any animal including humans.
- the animal are ruminant animals such as sheep, goats, cattle, deer, yank, camel, llama and kangaroo; and non-ruminant animals such as pigs (including but not limited to piglets, growing pigs, and sows), poultry (including but not limited to turkeys, ducks, quail, guinea fowl, geese, pigeons and chicken), horses, crustaceans (such as shrimps and prawns) and fishes.
- ruminant animals such as sheep, goats, cattle, deer, yank, camel, llama and kangaroo
- non-ruminant animals such as pigs (including but not limited to piglets, growing pigs, and sows), poultry (including but not limited to turkeys, ducks, quail, guinea fowl, geese, pigeon
- the animal is selected from the group consisting of sheep, goats, cattle, pigs (including but not limited to piglets, growing pigs, and sows), poultry (including but not limited to turkeys, ducks, quail, guinea fowl, geese, pigeons and chicken) and horses.
- sheep, goats, cattle, pigs including but not limited to piglets, growing pigs, and sows
- poultry including but not limited to turkeys, ducks, quail, guinea fowl, geese, pigeons and chicken
- the composition modulates growth of microorganisms in a synergistic model, i.e., it provides observed value (“O”) beyond the expected value (“E”) resulting from the individual ingredient of the composition, i.e, benzoic acid and/or salt thereof and the additional organic acid and/or salt thereof, in modulating growth of microorganisms.
- a synergistic model i.e., it provides observed value (“O”) beyond the expected value (“E”) resulting from the individual ingredient of the composition, i.e, benzoic acid and/or salt thereof and the additional organic acid and/or salt thereof, in modulating growth of microorganisms.
- the present invention provides a method for modulating growth of microorganisms, i.e., inhibiting the growth of pathogenic microorganisms and/or enhancing the growth of beneficial (i.e. probiotic) microorganisms, wherein the method comprises the steps of a) providing a composition as described herein; and b) contacting the composition of a) with the microorganisms.
- the present invention provides a method for modulating growth of microorganisms, especially for inhibiting the growth of pathogenic microorganisms, in a food and/or a feed, wherein the method comprises the steps of a) providing a composition as described herein; and b) contacting the composition of a) with the microorganisms in the food and/or the feed.
- the present invention provides a method for modulating growth of microorganisms in the gastrointestinal tracts, especially in the intestinal tracts (e.g. stomach, duodenum, jejunum, illeum, cecum, and/or large intestine) of animals and/or improving gut health of animals, wherein the method comprises the steps of a) providing a composition as described herein; and b) administering to the animals the composition of a).
- the intestinal tracts e.g. stomach, duodenum, jejunum, illeum, cecum, and/or large intestine
- the present invention provides a method for the treatment, amelioration and/or prevention of post-weaning diarrhea (PWD) of animals, such as pigs, wherein the method comprises the steps of a) providing a composition as described herein; and b) administering to the animals the composition of a).
- PWD post-weaning diarrhea
- the present invention provides a method for improving growth performance of animals, wherein the method comprises the steps of a) providing a composition as described herein; and b) administering to the animals the composition of a).
- the composition modulates growth of microorganisms, and/or treats, ameliorates and/or prevent PWD of animals, and/or improves growth performance of animals in a synergistic model, i.e., it provides observed value (“O”) beyond the expected value (“E”) resulting from the individual ingredient of the composition, i.e, benzoic acid and/or salt thereof and the additional organic acid and/or salt thereof, in modulating growth of microorganisms, and/or treatment, amelioration and/or prevention of PWD of animals, and/or improving growth performance of animals.
- a synergistic model i.e., it provides observed value (“O”) beyond the expected value (“E”) resulting from the individual ingredient of the composition, i.e, benzoic acid and/or salt thereof and the additional organic acid and/or salt thereof, in modulating growth of microorganisms, and/or treatment, amelioration and/or prevention of PWD of animals, and/or improving growth performance of animals.
- the present invention provides use of at least one additional organic acid and/or at least one salt thereof in the composition as defined above for boosting the effect of benzoic acid and/or at least one salt thereof in modulating growth of microorganisms, i.e., inhibiting the growth of pathogenic microorganisms and/or enhancing the growth of beneficial microorganisms,
- the present invention provides a method for boosting the effect of benzoic acid and/or at least one salt thereof in modulating growth of microorganisms, i.e., inhibiting the growth of pathogenic microorganisms and/or enhancing the growth of beneficial microorganisms, wherein the method comprises: a) providing a composition as described herein; and b) contacting the composition of a) with the microorganisms.
- the present invention provides a method for boosting the effect of benzoic acid and/or at least one salt thereof in modulating growth of microorganisms in the gastrointestinal tracts, especially in the intestinal tracts (e.g.
- PWD post-weaning diarrhea
- the term “boost” or “boosting” means that benzoic acid and/or at least one salt thereof and the at least one additional organic acid and/or at least one salt thereof in the composition according to the present invention modulates growth of microorganisms in a synergistic model, i.e., it provides observed value (“O”) beyond the expected value (“E”) resulting from the individual ingredient of the composition, i.e, benzoic acid and/orsaltthereof and the additional organic acid and/or salt thereof, in modulating growth of microorganisms.
- Example 1 Modulating growth of microorganisms
- the potential of the compositions of the present invention in modulating growth of microorganisms i.e., inhibiting the growth of the pathogenic microorganisms and enhancing the growth of the beneficial microorganisms, was studied.
- growth of the pathogenic microorganisms Escherichia coli (E. coli U5/41 (DSMZ 30083)
- Salmonella enterica S. enterica subsp. enterica serotype typhimurium SL1344 (DSMZ 24522)
- Shigella sonnei S.
- compositions of the present invention comprising either 0.2, 0.4, 0.8, 1.6, 3.1 , 6.3, 12.5, 25, 50 or 100 mM of either formic acid, acetic acid, propionic acid, fumaric acid or succinic acid; and/or either 0.3, 0.6, 1 .3, 2.5, 5, 10 or 20 mM of benzoic acid were prepared in Mueller-Hinton broth and sterilized by micro-filtration using a 0.22 pm filter. Either of the microorganisms listed above were cultivated in Mueller-Hinton broth (Mueller et al. 1941 . Experimental Biology and Medicine 48(1): 330- 333) until late exponential phase.
- Those liquid cultures were used to inoculate the compositions prepared as described above in 96-well microtiter plates to reach a final density of 5x10 5 cfu/mL.
- As sterility control one well containing Mueller-Hinton broth was not inoculated with microorganisms.
- growth control at least 4 wells of the 96-well microtiter plate were prepared, wherein only Mueller- Hinton broth was inoculated with either of the studied microorganisms.
- the growth controls were not treated with a composition as referred to herein comprising any organic acid and/or benzoic acid.
- the thus inoculated microtiter plates were incubated overnight at 37 °C under anaerobic conditions, provided by a saturated nitrogen atmosphere in anaerobic jars to simulate conditions in a gastrointestinal tract.
- the optical density at 600 nanometers (OD600) of each well of the incubated microtiter plates was measured approximately 20-26 h after incubation start, typically after approximately 24 h, using a multimode plate reader.
- the initial optical density value prior to overnight incubation was subtracted from the final value obtained after the overnight incubation period to calculate the growth values. These growth values were used to calculate the amount of inhibition or enhancement compared to the growth values of the growth control wells.
- the growth value of the growth control was 0.8308 after approximately 10 h
- the growth value of an E. coli culture comprising 12.5 mM formic acid was 0.6624
- the growth value of an E. coli culture comprising 12.5 mM benzoic acid was 0.7128
- E represents an expectation value
- X represents the degree of inhibition or enhancement observed upon treatment with a substance 1 (herein: organic acid(s) and/or salt(s) thereof); and “Y” represents the degree of inhibition or enhancement observed upon treatment with a substance 2 (herein: benzoic acid and/or salt(s) thereof).
- the expectation value indicates the theoretical amount of inhibition or enhancement that would be observable in case of merely additive (i.e. non-synergistic) inhibition of a combination of substance 1 and substance 2.
- X and Y are calculated in percent of inhibition or enhancement.
- a growth control that was not treated with substance 1 and/or substance 2 served as base value having no inhibition/enhancement, i.e. 0% of inhibition/enhancement.
- S represents the difference in the amount of inhibition or enhancement between the calculated additive inhibition (“E”) and the actually observed amount of inhibition or enhancement (“O”); “E” represents the expectation value as described above; and “O” denotes the observed amount of inhibition or enhancement.
- E calculated additive inhibition
- O actually observed amount of inhibition or enhancement
- S is a positive number, i.e. larger than 0, a combination of substance 1 and substance 2 was confirmed to inhibit or enhance the growth of the studied microorganisms synergistically.
- Synergistic modulation of microbial growth in particular synergistically inhibiting or enhancing the growth of the pathogenic microorganisms, was found upon treatment with compositions comprising a combination of i) one or more organic acid(s) with ii) benzoic acid.
- Tables 1-7 examples of synergistic inhibition or enhancement of the growth of the microorganisms by compositions according to the invention are shown.
- BA (mM) indicates the concentration of benzoic acid that was comprised in a composition as described above.
- OA (mM) indicates the concentration of organic acid(s) that was comprised in a composition as described above.
- the column labeled “BA:OA” indicates the molar ratio between benzoic acid and the additional organic acid(s) that was comprised in a composition as described above.
- the column labeled “details” indicates which organic acid was comprised in the composition.
- the synergistic inhibition effect (average “S” from two parallel experiments) is given in brackets after the organic acid with which the synergistic inhibition was observed in combination with benzoic acid.
- Table 1 Synergistic inhibition of the growth of E. coli U5/41 (DSMZ 30083) upon treatment with different concentrations of benzoic acid (BA) in combination with different concentrations of organic acid.
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Abstract
The present invention provides a composition for modulating growth of microorganisms, comprising at least one additional organic acid and/or at least one salt thereof, and benzoic acid and/or at least one salt thereof, and use thereof.
Description
A composition for modulating growth of microorganisms
Technical Field
The present invention relates to a composition for modulating growth of microorganisms and use thereof.
Background of the Invention
It is well known in the field of microbiology that the growth behavior of microorganisms depends on environmental conditions. Certain conditions may favor microbial growth while other conditions may reduce growth. Notably, certain environmental conditions may result in a growth reduction or even growth stagnation of some microorganisms, whereas other microorganisms may not be affected at all or may even show increased growth upon exposure to the same conditions.
In practice, environmental conditions are purposefully adapted by humans to either favor or disfavor microbial growth. For instance, efficient growth of selected suitable microorganisms such as bacteria or yeasts or fungi is desired in the feed industry, i.e. by the usage of silage inoculants or in the milk processing industry e.g. to produce yogurt or cheese. Further examples where a controlled increase of microbial growth is favored include fermentation processes such as beer brewing or wine making.
On the other hand, attempts are made to avoid or at least delay spoilage of nutritional products such as food, feedstock or feed due to uncontrolled growth of undesired microorganisms. In this regard, temperature conditions may be chosen to disfavor microbial growth. Typically, products subjected to a risk of microbial spoilage may be kept frozen or at least may be stored at low temperatures, e.g. below 10 °C. Further options to modulate or control microbial growth include the removal of water e.g. by lyophilization, smoking, salting, curing, sugaring or pickling. In some preservation processes, an acidic pH environment is established to disfavor the growth of unfavorable and potentially pathogenic microorganisms.
In this regard, acidifier products including organic acids may be used to maintain food and feed hygiene and prevent spoilage by microorganisms such as bacteria or molds. Organic acids e.g. formic acid, propionic acid or acetic acid as described in EP 2 642 874 may be used to control microbial growth in foodstuff, food or feed with the aim to minimize the risk for foodborne diseases. To this end, acidifier products may be added pre- and/or post-production of finished feed. Additionally, acidifier products may be used to achieve a reduced growth of potentially pathogenic
microorganisms in the gastrointestinal tract, but also to improve feed conversion rate and weight gain upon ingestion.
Notwithstanding the above, there is a constant need to improve said acidifier products, e.g. by improving the efficiency of the employed acids. It has now been found surprisingly that benzoic acid and/or at least one salt thereof, in combination with at least one additional organic acid and/or at least one salt thereof, provides enhanced antimicrobial effect.
Summary of the Invention
The present invention provides a composition for modulating growth of microorganisms, comprising a) benzoic acid and/or at least one salt thereof, and b) at least one additional organic acid and/or at least one salt thereof.
The present invention also provides use of the above composition for modulating growth of microorganisms, and a method by using the composition for modulating growth of microorganisms.
The present invention further provides use of at least one additional organic acid and/or at least one salt thereof in the composition as defined herein for boosting the effect of benzoic acid and/or at least one salt thereof in modulating growth of microorganisms.
Detailed description of the Invention
In the first aspect, the present invention provides a composition for modulating growth of microorganisms, wherein the composition comprises a) benzoic acid and/or at least one salt thereof, and b) at least one additional organic acid and/or at least one salt thereof.
In the present invention, the at least one salt of benzoic acid may be selected from the group consisting of sodium benzoate, magnesium benzoate, manganese benzoate, potassium hypophosphite, aluminium benzoate, calcium benzoate and ferric benzoate, preferably sodium benzoate, magnesium benzoate, manganese benzoate and potassium benzoate, and more preferably sodium benzoate.
In the present invention, the at least one additional organic acid is any organic acid other than benzoic acid, which may be selected from the group consisting of short monocarboxylic acids having between 1 and 6 carbon atom(s), saturated dicarboxylic acids, unsaturated dicarboxylic acids, unsaturated carboxylic acids, saturated carboxylic acids, hydroxycarboxylic acids, aromatic carboxylic acids, and/or keto carboxylic acids. Merely for clarification, examples of the short monocarboxylic acids having between 1 and 6 carbon atom(s) are formic acid, acetic acid, propionic acid, butyric acid, isobutyric acid, 3-methylbutyric acid, 2-methylbutyric acid, 2-ethylbutyric acid, valeric acid and
hexanoic acid. Examples of the saturated dicarboxylic acids are adipic acid and succinic acid. An example of the unsaturated dicarboxylic acid is fumaric acid. Examples of the unsaturated carboxylic acids are sorbic acid and oleic acid. Examples of the saturated carboxylic acids are stearic acid, octanoic acid (also referred to as caprylic acid), decanoic acid (also referred to as capric acid) and dodecanoic acid (also referred to as lauric acid). Examples of the hydroxycarboxylic acids are lactic acid, malic acid (D-, or L-, or D/L-malic acid), citric acid and tartaric acid. An example of the aromatic carboxylic acids is cinnamic acid. An example of the keto carboxylic acid is pyruvic acid.
Preferably, the at least one additional organic acid is selected from the group consisting of formic acid, acetic acid, propionic acid, butyric acid, isobutyric acid, 3-methylbutyric acid, 2-metylbutyric acid, 2-ethylbutyric acid, valeric acid, hexanoic acid, adipic acid, succinic acid, fumaric acid, sorbic acid, oleic acid, stearic acid, octanoic (caprylic) acid, decanoic (capric) acid, dodecanoic (lauric) acid, lactic acid, malic acid, citric acid, tartaric acid, cinnamic acid, pyruvic acid, gluconic acid, suberic acid, malonic acid, tannic acid, caffeic acid, ellagic acid, perillic acid and gallic acid.
More preferably, the at least one additional organic acid is selected from formic acid, acetic acid, propionic acid, butyric acid, isobutyric acid, 3-methylbutyric acid, 2-metylbutyric acid, 2-ethylbutyric acid, valeric acid, hexanoic acid, adipic acid, succinic acid, fumaric acid, sorbic acid, oleic acid, stearic acid, octanoic (caprylic) acid, decanoic (capric) acid, dodecanoic (lauric) acid, lactic acid, malic acid, citric acid, tartaric acid, cinnamic acid and pyruvic acid, or at least one salt thereof.
Further preferably, the at least one additional organic acid is selected from formic acid, acetic acid, propionic acid, fumaric acid and succinic acid. The most preferably, the at least one additional organic acid is selected from fumaric acid and succinic acid.
In the present invention, the at least one salt of the additional organic acid may be any one of metal salts such as potassium, sodium or calcium salts, and ammonium salts. Examples of the salts of the organic acid include but are not limited to ammonium formate, potassium diformate, sodium diacetate, calcium acetate, ammonium propionate, sodium propionate, calcium propionate, calcium lactate, potassium sorbate, sodium formate, calcium formate, sodium butyrate, sodium sorbate, potassium citrate, sodium citrate and calcium citrate.
In some embodiments, the composition according to the invention may comprise benzoic acid and/or at least one salt thereof in combination with more than one additional organic acid and/or at least one salt thereof. For example, such a composition may comprise benzoic acid and/or at least one salt thereof in combination with two, three, four, five or even more additional organic acids. In preferable embodiments, the composition comprises benzoic acid and/or a salt of benzoic acid and at least three additional organic acids, especially formic acid, acetic acid and propionic acid, wherein the salt of benzoic acid is selected from the group consisting of sodium benzoate, manganese benzoate,
magnesium benzoate and potassium benzoate, preferably sodium benzoate or manganese benzoate, more preferably sodium benzoate. In more preferable embodiments, the composition according to the invention comprises benzoic acid and/or a salt of benzoic acid and at least four additional organic acids, especially formic acid, acetic acid, propionic acid and fumaric acid, wherein the salt of benzoic acid is selected from the group consisting of sodium benzoate, manganese benzoate, magnesium benzoate and potassium benzoate, preferably sodium benzoate or manganese benzoate, more preferably sodium benzoate. In further preferable embodiments, the composition according to the invention comprises benzoic acid and/or a salt of benzoic acid and at least five additional organic acids, especially formic acid, acetic acid, propionic acid, fumaric acid and succinic acid, wherein the salt of benzoic acid is selected from the group consisting of sodium benzoate, manganese benzoate, magnesium benzoate and potassium benzoate, preferably sodium benzoate or manganese benzoate, more preferably sodium benzoate.
The composition of the present application may be formulated in the form of a feed additive (premix) or a food additive or a feed or a food for administering to animals. Accordingly, Such a composition may further comprise components, such as one or more of the following: Fat- or water-soluble vitamin(s), trace- and/or macro-mineral(s), (proteinogenic) amino acid(s), organic and/or inorganic adsorbant(s), polyunsaturated fatty acid(s), antimicrobial polypeptide(s), pre- and/or pro-biotic(s), flavoring and/or coloring agent(s), microorganism(s) and/or enzyme(s) to facilitate better nutrient availability and/or to mitigate undesired effects) of feed/food contaminants).
Such a composition according to the invention may be provided in a form wherein one or more or all of the components is/are provided in solid form (e.g. salt, powder, granulate, pellet etc.) or in liquid form (e.g. aqueous, gel, viscous). It is also considered that the composition may be provided in a manner, wherein one component (e.g. one or more organic acid(s)) is provided in liquid form and a second component is provided in solid form (e.g. benzoic acid), and the composition is formed by combining the two components in a mixture or in a separate form.
According to the present invention, said composition may be provided in a particular manner, wherein the molar ratio of the at least one additional organic acid and/or the at least one salt thereof to benzoic acid and/or the at least one salt thereof is from 0.001 :1 to 500:1 , preferably from 0.005:1 to 300:1 , more preferably from 0.01 :1 to 200:1 , such as from 0.01 :1 to 0.15:1 , from 0.02:1 to 0.1 :1 , from 0.04:1 to 100:1 , from 0.05:1 to 100:1 , , from 0.1 :1 to 100:1 , from 1 :1 to 100:1 , from 10:1 to 80:1 and from 20:1 to 40:1. For instance, the at least one additional organic acid and/or the at least one salt thereof may be provided at any concentration from 0.2 mmol to 100 mmol such as 0.2. 0.4, 0.8. 1.5, 3.1 , 6.25, 12.5, 25.0, 50.0 and 100 mmol, in combination with benzoic acid and/or at least one salt thereof at any concentration from 0.2 mmol to 20 mmol such as 0.3, 0.6, 1 .3, 2.5, 5.0, 10 and 20 mmol, per 1 Kg of the composition in solid form or per 1 L of the composition in liquid form. Preferably, in the composition of the present invention, the molar ratio of the at least one additional organic acid and/or
the at least one salt thereof to benzoic acid and/or the at least one salt thereof is in the range of from 0.001 :1 to 0.15:1.
The composition of the present invention can be used for modulating growth of microorganisms, i.e., inhibiting the growth of pathogenic microorganisms and/or enhancing the growth of beneficial (i.e. probiotic) microorganisms.
In the present invention, the microorganisms may be any one or more of the genera of Butiauxella, Citrobacter, Cronobacter, Enterobacter, Escherichia, Edwardsiella, Klebsiella, Phytobacter, Plesiomonas, Pseudoescherichia, Raoultella, Salmonella, Shigella, Proteus, Yersinia, Vibrio, Aeromonas, Clostridium, Pseudomonas, Staphylococcus, Pasteurella, Brachyspira, Campylobacter, Listeria, Streptococcus, Haemophilus, Brucella, Moritella, Tenacibaculum, Lactobacillus, Bifidobacterium, Saccharomyces, Bacillus, Pediococcus, Enterococcus, Streptococcus, Propionibacterium, Pseudomonas and Citrobacter. Particularly, the microorganisms in the present invention may be any one or more of Escherichia coll, Salmonella enterica, Shigella sonnei, Clostridium perfringens, Lactobacillus reuteri, Enterococcus faecium and Bacillus subtilis.
Particularly, the pathogenic microorganisms in the present invention may be at least one of the genera of Buttiauxella, Citrobacter, Cronobacter, Enterobacter, Escherichia, Edwardsiella, Klebsiella, Phytobacter, Plesiomonas, Pseudoescherichia, Raoultella, Salmonella, Shigella, Proteus, Yersinia, Vibrio, Aeromonas, Clostridium, Pseudomonas, Staphylococcus, Pasteurella, Brachyspira, Campylobacter, Listeria, Streptococcus, Haemophilus, Brucella, Moritella and Tenacibaculum, in particular may be selected from the group consisting of Escherichia coli, Salmonella enterica, Shigella sonnei and Clostridium perfringens.
Particularly, the beneficial microorganisms in the present invention may be at least one microorganism selected from the genera of Lactobacillus, Bifidobacterium, Saccharomyces, Bacillus, Pediococcus, Enterococcus, Streptococcus, Propionibacterium, Pseudomonas and Citrobacter, in particular may be selected from the group consisting of Lactobacillus reuteri, Enterococcus faecium and Bacillus subtilis.
It was unexpectedly found that the composition of the present invention was capable of modulating growth of microorganisms in a synergistic model. In the present invention, the term “in a synergistic model” means that, in a test of modulating growth of microorganisms, for example, according to the example 1 of the present invention, the composition of the present invention provides observed value (“O”) beyond the expected value (“E”) resulting from the individual ingredient of the composition, i.e, benzoic acid and/or salt thereof and the additional organic acid and/or salt thereof. In the present invention, the expected value (“E”) can be calculated according to the formula developed by Colby etal. (1967. Weeds 15(1): 20-22), which is incorporated herein as reference. In the present invention,
the expression “observed value (“O”) beyond the expected value (“E”)” means that the result of the observed value minus the expected value, i.e., E - O, is bigger than zero (0), preferably no less than 1 , 2, 3, 5, 8 10, and more preferably no less than 10.
Accordingly, the present invention also provides a composition as described above, wherein in a test of modulating growth of microorganisms the composition of the present invention provides observed value (“O”) beyond the expected value (“E”) resulting from the individual ingredient of the composition, i.e, benzoic acid and/or salt thereof and the additional organic acid and/or salt thereof.
In the present invention, the composition may comprise benzoic acid and/or at least one salt thereof and the at least one additional organic acid and/or at least one salt thereof as the only active ingredients for modulating growth of microorganisms. However, the composition of the present invention, besides benzoic acid and/or at least one salt thereof and the at least one additional organic acid and/or at least one salt thereof, may comprises additional active ingredients such as enzymes for modulating growth of microorganisms.
In the second aspect, the present invention provides use of the composition as described herein for modulating growth of microorganisms, i.e., inhibiting the growth of pathogenic microorganisms and/or enhancing the growth of beneficial (i.e. probiotic) microorganisms.
As understood by any person skilled in the art, the microorganisms may be present in a food and /or a feed, and/or in the gastrointestinal tracts of animals. In some embodiments, the present invention provides use of the composition as described herein for modulating growth of microorganisms, especially for inhibiting the growth of pathogenic microorganisms, in a food and/or a feed. In some embodiments, the present invention provides use of the composition as described herein for modulating growth of microorganisms in the gastrointestinal tract, especially in the intestinal tracts (e.g. stomach, duodenum, jejunum, illeum, cecum, and/or large intestine) of animals. In some preferable embodiment, the present invention provides use of the composition as described herein for improving gut health of animals.
In some special embodiments, the present invention provides use of the composition as described herein for the treatment, amelioration and/or prevention of post-weaning diarrhea (PWD) of animals, such as pigs. PWD is often caused by strains of Escherichia coll in the gastrointestinal tract of animals (e.g. Fairbrother et al. 2005. Anim Health Res Rev. 6(1):17-39), resulting in considerable economic loss and animal malady. Notably, growth of such strains can be reduced in the gastrointestinal tract of animals (e.g. pigs) by administering to the animals the composition described herein, and thereby PWD can be treated, ameliorated and/or prevented. As understood by any person skilled in the art, the treatment, amelioration and/or prevention of PWD can be characterized by for example increased
faeces score. Preferably, in the present invention, the faeces score is increased by at least 1%, 2%, 3%, 5%, 10% or more.
In other special embodiments, the present invention provides use of the composition as described herein for improving growth performance of animals. As anticipated by any person skilled in the art, one or more of the characters of growth performance such as weight gain, daily weight gain, feed intake, daily feed intake, feed conversion ratio and/or mortality ratio of animals could be improved because of the effect of the composition as described herein in modulating growth of microorganisms in the gastrointestinal tract of animals. Preferably, any of the characters of growth performance is improved by at least 1 %, 2%, 3%, 5%, 10%, 15%, 20% or more because of the composition as described herein.
In the present invention, the terms “food” and “feed” are used to refer to any component, ingredient, preparation, mixture or additive suitable for, or intended for oral intake by animals. Examples of the food and/or the feed include but are not limited to foodstuff; fodder; feed; silage; foodstuff additive; fodder additive; feed additive; silage additive; feed or food components such as crop, grain such as wet distillers grain and dried distillers grain, hay, straw, protein sources such as soy protein, starch and carbohydrates etc.; nutritional supplement; prebiotic; probiotic; intermed iate/s thereof; and/or mixture/s thereof.
In the present invention, the term “animal” or "animals" refers to any animal including humans. Examples of the animal are ruminant animals such as sheep, goats, cattle, deer, yank, camel, llama and kangaroo; and non-ruminant animals such as pigs (including but not limited to piglets, growing pigs, and sows), poultry (including but not limited to turkeys, ducks, quail, guinea fowl, geese, pigeons and chicken), horses, crustaceans (such as shrimps and prawns) and fishes. Preferably, the animal is selected from the group consisting of sheep, goats, cattle, pigs (including but not limited to piglets, growing pigs, and sows), poultry (including but not limited to turkeys, ducks, quail, guinea fowl, geese, pigeons and chicken) and horses.
Preferably, in the use ofthe present invention, the composition modulates growth of microorganisms in a synergistic model, i.e., it provides observed value (“O”) beyond the expected value (“E”) resulting from the individual ingredient of the composition, i.e, benzoic acid and/or salt thereof and the additional organic acid and/or salt thereof, in modulating growth of microorganisms.
In the third aspect, the present invention provides a method for modulating growth of microorganisms, i.e., inhibiting the growth of pathogenic microorganisms and/or enhancing the growth of beneficial (i.e. probiotic) microorganisms, wherein the method comprises the steps of a) providing a composition as described herein; and b) contacting the composition of a) with the microorganisms.
In some embodiments, the present invention provides a method for modulating growth of microorganisms, especially for inhibiting the growth of pathogenic microorganisms, in a food and/or a feed, wherein the method comprises the steps of a) providing a composition as described herein; and b) contacting the composition of a) with the microorganisms in the food and/or the feed.
In some other embodiments, the present invention provides a method for modulating growth of microorganisms in the gastrointestinal tracts, especially in the intestinal tracts (e.g. stomach, duodenum, jejunum, illeum, cecum, and/or large intestine) of animals and/or improving gut health of animals, wherein the method comprises the steps of a) providing a composition as described herein; and b) administering to the animals the composition of a).
In some special embodiments, the present invention provides a method for the treatment, amelioration and/or prevention of post-weaning diarrhea (PWD) of animals, such as pigs, wherein the method comprises the steps of a) providing a composition as described herein; and b) administering to the animals the composition of a).
In other special embodiments, the present invention provides a method for improving growth performance of animals, wherein the method comprises the steps of a) providing a composition as described herein; and b) administering to the animals the composition of a).
Preferably, in the methods of the present invention, the composition modulates growth of microorganisms, and/or treats, ameliorates and/or prevent PWD of animals, and/or improves growth performance of animals in a synergistic model, i.e., it provides observed value (“O”) beyond the expected value (“E”) resulting from the individual ingredient of the composition, i.e, benzoic acid and/or salt thereof and the additional organic acid and/or salt thereof, in modulating growth of microorganisms, and/or treatment, amelioration and/or prevention of PWD of animals, and/or improving growth performance of animals.
In the fourth aspect, the present invention provides use of at least one additional organic acid and/or at least one salt thereof in the composition as defined above for boosting the effect of benzoic acid and/or at least one salt thereof in modulating growth of microorganisms, i.e., inhibiting the growth of pathogenic microorganisms and/or enhancing the growth of beneficial microorganisms,
Particularly, the present invention provides a method for boosting the effect of benzoic acid and/or at least one salt thereof in modulating growth of microorganisms, i.e., inhibiting the growth of pathogenic microorganisms and/or enhancing the growth of beneficial microorganisms, wherein the method comprises: a) providing a composition as described herein; and b) contacting the composition of a) with the microorganisms.
Specially, the present invention provides a method for boosting the effect of benzoic acid and/or at least one salt thereof in modulating growth of microorganisms in the gastrointestinal tracts, especially in the intestinal tracts (e.g. stomach, duodenum, jejunum, illeum, cecum, and/or large intestine) of animals, and/or in improving gut health of animals, and/or in the treatment, amelioration and/or prevention of post-weaning diarrhea (PWD) of animals, such as pigs, wherein the method comprises the steps of a) providing a composition as described herein; and b) administering to the animals the composition of a).
In the present invention, the term “boost” or "boosting" means that benzoic acid and/or at least one salt thereof and the at least one additional organic acid and/or at least one salt thereof in the composition according to the present invention modulates growth of microorganisms in a synergistic model, i.e., it provides observed value (“O”) beyond the expected value (“E”) resulting from the individual ingredient of the composition, i.e, benzoic acid and/orsaltthereof and the additional organic acid and/or salt thereof, in modulating growth of microorganisms.
The present invention is further illustrated by the following examples.
Examples
Example 1 : Modulating growth of microorganisms
In the example, the potential of the compositions of the present invention in modulating growth of microorganisms, i.e., inhibiting the growth of the pathogenic microorganisms and enhancing the growth of the beneficial microorganisms, was studied. In a systematic approach, growth of the pathogenic microorganisms: Escherichia coli (E. coli U5/41 (DSMZ 30083)), Salmonella enterica (S. enterica subsp. enterica serotype typhimurium SL1344 (DSMZ 24522)), Shigella sonnei (S. sonnei ATCC 29930, I virulent, WDCM 00127, CECT 4887 (DSMZ 5570)) and Clostridium perfringens (C. perfringens (CCUG 47895; type A as described in Johansson et al. 2004. Vet Microbiol. 99(3-4)): 251-257); and the beneficial microorganisms: Lactobacillus reuteri (L. reuteri F 275 (DSMZ 20016)), Enterococcus faecium (E. faecium D, serotype 11 (DSMZ 20477)) and Bacillus subtilis (B. subtilis strain Marburg (DSMZ 10)) was recorded and the synergistic effect was assessed.
In particular, the compositions of the present invention comprising either 0.2, 0.4, 0.8, 1.6, 3.1 , 6.3, 12.5, 25, 50 or 100 mM of either formic acid, acetic acid, propionic acid, fumaric acid or succinic acid; and/or either 0.3, 0.6, 1 .3, 2.5, 5, 10 or 20 mM of benzoic acid were prepared in Mueller-Hinton broth and sterilized by micro-filtration using a 0.22 pm filter. Either of the microorganisms listed above were cultivated in Mueller-Hinton broth (Mueller et al. 1941 . Experimental Biology and Medicine 48(1): 330- 333) until late exponential phase. Those liquid cultures were used to inoculate the compositions prepared as described above in 96-well microtiter plates to reach a final density of 5x105 cfu/mL. As
sterility control, one well containing Mueller-Hinton broth was not inoculated with microorganisms. As growth control, at least 4 wells of the 96-well microtiter plate were prepared, wherein only Mueller- Hinton broth was inoculated with either of the studied microorganisms. In other words, the growth controls were not treated with a composition as referred to herein comprising any organic acid and/or benzoic acid.
The thus inoculated microtiter plates were incubated overnight at 37 °C under anaerobic conditions, provided by a saturated nitrogen atmosphere in anaerobic jars to simulate conditions in a gastrointestinal tract. To evaluate the growth of the microorganisms, the optical density at 600 nanometers (OD600) of each well of the incubated microtiter plates was measured approximately 20-26 h after incubation start, typically after approximately 24 h, using a multimode plate reader. The initial optical density value prior to overnight incubation was subtracted from the final value obtained after the overnight incubation period to calculate the growth values. These growth values were used to calculate the amount of inhibition or enhancement compared to the growth values of the growth control wells. For instance, if the growth value of the growth control was 0.8308 after approximately 10 h, the growth value of an E. coli culture comprising 12.5 mM formic acid was 0.6624, the growth value of an E. coli culture comprising 12.5 mM benzoic acid was 0.7128, and the growth value of an E. coli culture comprising 12.5 mM formic acid and 12.5 mM benzoic acid was 0.3692, then the growth of the culture comprising 12.5 mM formic acid compared to the growth of the growth control would be calculated as 0.6624x100/0.8308 = 79.72%, the growth of the culture comprising 12.5 mM benzoic acid compared to the growth of the growth control would be calculated as 0.7128x100/0.8308 = 85.80%, and the growth of the culture comprising 12.5 mM formic acid and 12.5 mM benzoic acid compared to the growth of the growth control would be calculated as 0.3692x100/0.8308 = 44.44%. In other words, the composition comprising 12.5 mM formic acid inhibited the microbial growth by 100-79.92 = 20.28%, the composition comprising 12.5 mM benzoic acid inhibited the microbial growth by 100-85.80 = 14.20%, and the composition comprising 12.5 mM formic acid and 12.5 mM benzoic acid inhibited the microbial growth by 100-44.44 = 55.56%.
Synergistic inhibition or enhancement was assessed as published by Colby et al. (1967. Weeds 15(1): 20-22) using the following formula:
E = X + (Y/100) x (100-X)
Therein, “E” represents an expectation value; “X” represents the degree of inhibition or enhancement observed upon treatment with a substance 1 (herein: organic acid(s) and/or salt(s) thereof); and “Y” represents the degree of inhibition or enhancement observed upon treatment with a substance 2 (herein: benzoic acid and/or salt(s) thereof). The expectation value indicates the theoretical amount of inhibition or enhancement that would be observable in case of merely additive (i.e. non-synergistic) inhibition of a combination of substance 1 and substance 2. Both, “X” and “Y” are calculated in percent
of inhibition or enhancement. A growth control that was not treated with substance 1 and/or substance 2, served as base value having no inhibition/enhancement, i.e. 0% of inhibition/enhancement.
In a next step, the actually observed amount of inhibition or enhancement of a combination of substance 1 and substance 2 was compared to the expectation value, and used to quantify the synergy according to the following formula:
S = O - E
Therein, “S” represents the difference in the amount of inhibition or enhancement between the calculated additive inhibition (“E”) and the actually observed amount of inhibition or enhancement (“O”); “E” represents the expectation value as described above; and “O” denotes the observed amount of inhibition or enhancement. In the event that “S” is a positive number, i.e. larger than 0, a combination of substance 1 and substance 2 was confirmed to inhibit or enhance the growth of the studied microorganisms synergistically.
For instance, in the example above, wherein a composition comprising 12.5 mM formic acid inhibited the microbial growth by 20.28%, a composition comprising 12.5 mM benzoic acid inhibited the microbial growth by 14.20%, the expectation value “E” would be calculated as 20.28+(14.20/100)x (100-20.28) = 31.60%. In other words, in case of an additive or non-synergistic inhibition, a composition comprising both 12.5 mM formic acid and 12.5 mM benzoic acid would be expected to inhibit the microbial growth by 31 .60%. However, in contrast to this expectation, the microbial growth was experimentally determined to be inhibited by 55.56%. Thus, “S” would be calculated as 55.56- 31.60 = 23,96%, indicating synergistic inhibition.
Synergistic modulation of microbial growth, in particular synergistically inhibiting or enhancing the growth of the pathogenic microorganisms, was found upon treatment with compositions comprising a combination of i) one or more organic acid(s) with ii) benzoic acid. In the following Tables 1-7, examples of synergistic inhibition or enhancement of the growth of the microorganisms by compositions according to the invention are shown. Therein, the column labeled “BA (mM)” indicates the concentration of benzoic acid that was comprised in a composition as described above. The column labeled “OA (mM)” indicates the concentration of organic acid(s) that was comprised in a composition as described above. The column labeled “BA:OA” indicates the molar ratio between benzoic acid and the additional organic acid(s) that was comprised in a composition as described above. The column labeled “details” indicates which organic acid was comprised in the composition. And in addition, the synergistic inhibition effect (average “S” from two parallel experiments) is given in brackets after the organic acid with which the synergistic inhibition was observed in combination with benzoic acid.
Table 1. Synergistic inhibition of the growth of E. coli U5/41 (DSMZ 30083) upon treatment with different concentrations of benzoic acid (BA) in combination with different concentrations of organic acid.
Table 2. Synergistic inhibition of the growth of S. enterica subsp. enterica serotype typhimurium SL1344 (DSMZ 24522) upon treatment with different concentrations of benzoic acid (BA) in combination with different concentrations of organic acid.
Table 3. Synergistic inhibition of the growth of S. sonnei ATCC 29930, I virulent, WDCM 00127, CECT 4887 (DSMZ 5570) upon treatment with different concentrations of benzoic acid (BA) in combination with different concentrations of organic acid.
Table 4. Synergistic inhibition of the growth of C. perfringens (CCUG 47895; type A as described in Johansson etal. 2004. Vet Microbiol. 99(3-4): 251-257) upon treatment with different concentrations of benzoic acid (BA) in combination with different concentrations of organic acid.
Table 5. Synergistic enhancement of the growth of L. reuteri F 275 (DSMZ 20016) upon treatment with different concentrations of benzoic acid (BA) in combination with different concentrations of organic acid.
Table 6. Synergistic enhancement of the growth of E. faecium D, serotype 11 (DSMZ 20477) upon treatment with different concentrations of benzoic acid (BA) in combination with different concentrations of organic acid.
Claims
Claims A composition for modulating growth of microorganisms, wherein the composition comprises a) benzoic acid and/or at least one salt thereof, and b) at least one additional organic acid and/or at least one salt thereof, wherein the composition modulates the growth of microorganisms in a synergistic model. The composition of claim 1 , wherein the at least one additional organic acid is selected from the group consisting of short monocarboxylic acids having between 1 and 6 carbon atom(s), saturated dicarboxylic acids, unsaturated dicarboxylic acids, unsaturated carboxylic acids, saturated carboxylic acids, hydroxycarboxylic acids, aromatic carboxylic acids, and/or keto carboxylic acids. The composition of claim 1 , wherein the at least one additional organic acid is selected from the group consisting of formic acid, acetic acid, propionic acid, butyric acid, isobutyric acid, 3- methylbutyric acid, 2-metylbutyric acid, 2-ethylbutyric acid, valeric acid, hexanoic acid, adipic acid, succinic acid, fumaric acid, sorbic acid, oleic acid, stearic acid, octanoic acid, decanoic acid, dodecanoic (lauric) acid, lactic acid, malic acid, citric acid, tartaric acid, cinnamic acid, pyruvic acid, gluconic acid, suberic acid, malonic acid, tannic acid, caffeic acid, ellagic acid, perillic acid and gallic acid. The composition of claim 1 , wherein the at least one additional organic acid is selected from the group consisting of formic acid, acetic acid, propionic acid, fumaric acid and succinic acid, preferably fumaric acid and succinic acid. The composition any one of claims 1-4, wherein the at least one salt of the organic acid is any one of metal salts such as potassium, sodium and calcium salts, and ammonium salts. The composition of claim 1 , wherein the at least one salt of benzoic acid is selected from the group consisting of sodium benzoate, magnesium benzoate, manganese benzoate, potassium hypophosphite, aluminium benzoate, calcium benzoate and ferric benzoate. The composition of any one of claims 1-6, wherein the molar ratio of the at least one additional organic acid and/or the at least one salt thereof to benzoic acid and/or the at least one salt thereof is 0.001 :1 to 500:1 , preferably from 0.005:1 to 300:1 , more preferably from 0.01 :1 to 200:1 , such as from 0.01 :1 to 0.15:1 , from 0.02:1 to 0.1 :1 , from 0.04:1 to 100:1 , from 1 :1 to 100:1 , from 10:1 to 80:1 and from 20:1 to 40:1 . The composition of any one of claims 1-6, wherein the at least one additional organic acid and/or the at least one salt thereof is provided at any concentration from 0.2 mmol to 100 mmol, in combination with benzoic acid and/or at least one salt thereof at any concentration from 0.2
mmol to 20 mmol, per 1 Kg of the composition in solid form or per 1 L of the composition in liquid form.
9. The composition of any one of claims 1-8, wherein the composition comprises benzoic acid and/or at least one salt thereof and the at least one additional organic acid and/or at least one salt thereof as the only active ingredients for modulating growth of microorganisms.
10. The composition of any one of claims 1 -9, wherein the microorganisms is any one or more of the genera of Butiauxella, Citrobacter, Cronobacter, Enterobacter, Escherichia, Edwardsiella, Klebsiella, Phytobacter, Plesiomonas, Pseudoescherichia, Raoultella, Salmonella, Shigella, Proteus, Yersinia, Vibrio, Aeromonas, Clostridium, Pseudomonas, Staphylococcus, Pasteurella, Brachyspira, Campylobacter, Listeria, Streptococcus, Haemophilus, Brucella, Moritella, Tenacibaculum, Lactobacillus, Bifidobacterium, Saccharomyces, Bacillus, Pediococcus, Enterococcus, Streptococcus, Propionibacterium, Pseudomonas and Citrobacter, preferably /s selected from the group consisting of Escherichia coll, Salmonella enterica, Shigella sonnei, Clostridium perfringens, Lactobacillus reuteri, Enterococcus faecium and Bacillus subtilis.
11. Use of the composition according to any one of claims 1-10 for modulating growth of microorganisms.
12. Use of the composition according to any one of claims 1-10 for modulating growth of microorganisms in the gastrointestinal tract of animals, and/or for improving gut health of animals, and/or for the treatment, amelioration and/or prevention of post-weaning diarrhea (PWD), and/or improving growth performance of animals.
13. Use of claim 11 or 12, wherein the animal is selected from the group consisting of sheep, goats, cattle, pigs (including but not limited to piglets, growing pigs, and sows), poultry (including but not limited to turkeys, ducks, quail, guinea fowl, geese, pigeons and chicken) and horses.
14. Use of at least one additional organic acid and/or at least one salt thereof in the composition according to any one of claims 1-10 for boosting the effect of benzoic acid and/or at least one salt thereof in modulating growth of microorganisms.
15. A method for modulating growth of microorganisms, wherein the method comprises the steps of a) providing the composition according to any one of claims 1-10; and b) contacting the composition of a) with the microorganisms.
16. A method for modulating growth of microorganisms in the gastrointestinal tracts of animals, and/or for improving gut health of animals, and/or for the treatment, amelioration and/or prevention of post-weaning diarrhea (PWD), improving growth performance of animals, wherein the method comprises the steps of a) providing the composition according to any one of claims 1-10; and b) administering to the animals the composition of a).
17. A method for boosting the effect of benzoic acid and/or at least one salt thereof in modulating growth of microorganisms, wherein the method comprises: a) providing the composition according to any one of claims 1-10; and b) contacting the composition of a) with the
5 microorganisms.
18. A method for boosting the effect of benzoic acid and/or at least one salt thereof in modulating growth of microorganisms in the gastrointestinal tracts of animals, and/or in improving gut health of animals, and/or in the treatment, amelioration and/or prevention of post-weaning diarrhea w (PWD) of animals, wherein the method comprises the steps of a) providing the composition according to any one of claims 1-10; and b) administering to the animals the composition of a).
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