Production of bioactive oligosaccharides
阅读说明：本技术 生物活性寡糖的生产 (Production of bioactive oligosaccharides ) 是由 M·J·阿米促茨 D·派克 A·G·加勒莫 D·A·迈尔斯 J·B·格曼 C·B·莱布拉 于 2018-06-19 设计创作，主要内容包括：提供了产生寡糖的方法。(Methods of producing oligosaccharides are provided.)
1. A method of producing oligosaccharides from a polysaccharide, the method comprising:
reacting a polysaccharide with hydrogen peroxide and a transition metal or an alkaline earth metal in a reaction mixture; the reaction is then quenched with base and/or the glycosidic linkages in the polysaccharide are cleaved with base, thereby producing an oligosaccharide mixture from the polysaccharide.
2. The method of claim 1, wherein the reaction mixture comprises a transition metal.
3. The method of claim 2, wherein the transition metal is selected from iron (e.g., Fe)3+、Fe2+) Copper (e.g., Cu)2+) Manganese, cobalt or molybdenum.
4. The method of claim 1, wherein the reaction mixture comprises an alkaline earth metal.
5. The process of claim 4 wherein the alkaline earth metal is selected from calcium or magnesium.
6. The method of claim 1 or 3, wherein the transition metal concentration in the reaction mixture is at least 0.65 nM.
7. The method of claim 1 or 3, wherein the transition metal concentration in the reaction mixture is from 0.65nM to 500 nM.
8. The process of claim 1, wherein the hydrogen peroxide concentration in the reaction mixture is at least 0.02M.
9. The process of claim 1, wherein the hydrogen peroxide concentration in the reaction mixture is from 0.02M to 1M.
10. The process of claim 1, wherein the base is sodium hydroxide, potassium hydroxide or calcium hydroxide.
11. The method of claim 1 or 10, wherein the concentration of base is at least 0.1M.
12. The method of claim 1 or 10, wherein the concentration of the base is 0.1M to 5.0M.
13. The method of claim 1 wherein the polysaccharide comprises one or more of amylose, amylopectin, β -glucan, amylopectin, xyloglucan, arabinogalactan I and II, rhamnogalacturonan I, rhamnogalacturonan II, galactan, arabinogalactan, arabinoxylan, xylan, glycogen, mannan, glucomannan, curdlan, or inulin.
14. The method of claim 1, wherein the polysaccharide is from a plant or animal source.
15. The method of claim 1, wherein the polysaccharide is from a bacterial, fungal or algal source.
16. The method of claim 1, wherein the polysaccharide is in the form of a plant material.
17. The method of claim 1, wherein the plant material is banana, chickpea or millet plant material.
18. The method of any one of claims 1-17, further comprising purifying one or more oligosaccharides from the oligosaccharide mixture.
19. The process of any one of claims 1 to 18, wherein prior to the reaction, the process comprises contacting the polysaccharide with one or more polysaccharide degrading enzymes.
20. The method of claim 19, wherein one or more polysaccharide degrading enzymes comprises an amylase, an isoamylase, a cellulase, a maltase, a glucanase, or a combination thereof.
21. A composition comprising the oligosaccharide mixture of any one of claims 1-17 or purified oligosaccharide(s) of claim 18.
22. An oligosaccharide from table 1, or a mixture of two or more oligosaccharides from table 1.
23. A method of stimulating the growth of a microorganism in vitro or in vivo, the method comprising:
contacting a microorganism with a composition comprising the oligosaccharide mixture of claim 21 or the oligosaccharide of the mixture of claim 22 under conditions which selectively stimulate the growth of a prebiotic microorganism.
24. The method of claim 23, wherein the microorganism is a prebiotic microorganism.
25. The method of claim 24 wherein the prebiotic microorganism is administered to the animal in the gut of the animal.
26. The method of claim 25 wherein the prebiotic microorganism is administered to the animal independently of or in conjunction with the composition.
27. The method of any one of claims 24-26, wherein the probiotic microorganism is Bifidobacterium pseudocatenulatum (Bifidobacterium pseudocatenulatum).
28. The method of claim 23, wherein the microorganism is a soil microorganism, an oral microorganism, or a skin microorganism.
Background
Sugar molecules short chains of 3-20 monosaccharides in length are called oligosaccharides and are of particular interest due to their biological activity. This includes its ability to act as a prebiotic, modulate the immune system, hinder adhesion of pathogens in the gut [ Hooper, l.v.; midtvedt, t.; gordon, J.I., Annual review of nutrition 2002,22(1), 283-. The most preferable examples of these oligosaccharides are oligosaccharides produced in human milk [ LoCascio, R.G., et al, Journal of agricultural and food chemistry 2007,55(22), 8914-8919; marcobal, A. et al, Journal of agricultural and food chemistry 2010,58(9), 5334; wang, M. et al, Journal of pediaturico gastroenterology and nutrition 2015,60(6),825 ]. These compounds are known to have a high specificity of enriching the intestinal tract of the newborn with specific bacteria.
There have been many attempts to collect oligosaccharides from plant and animal based products. Examples include galacto-oligosaccharides (GOS) [ Lamsal, B.P., Journal of the Science of Food and Agriculture 2012,92(10), 2020-. These products are currently used for nutritional and pharmaceutical applications.
Short-chain unconjugated oligosaccharide chains are not readily found in nature, except for human milk oligosaccharides. Furthermore, these compounds are very expensive to synthesize and difficult to isolate, since oligosaccharides are not abundant in most natural products. Polysaccharides (i.e., sugar molecules up to 100,000 monosaccharides in length) are naturally present in plants, bacteria, and yeasts in great abundance, but they are too large to be biologically active.
Fenton (Fenton) chemistry is based on the generation of hydroxyl and hydrogen peroxide radicals with iron catalysts [ Neyens, e.; baeyens, J., Journal of Hazardous materials 2003,98(1), 33-50; walling, C., Accounts of chemical research 1975,8(4),125-131]These free radical products can in turn oxidize a number of different substrates [ Kuo, W., Water Research 1992,26(7), 881-; lin, s.h.; lo, c.c., waters research 1997,31(8), 2050-; watts, r.j. et al, Hazardous wale and Hazardous materials 1990,7(4), 335-; zazo, J. et al, Environmental science&technology 2005,39(23),9295-9302]. Notably, fenton oxidation is used as an analytical tool to determine the interaction between nucleic acid complexes and proteins by selective cleavage of the respective polymers [ Meares, c.f. et al, Methods in enzymology2003,371, 82-106; rana, t.m.; meares, C.F., Journal of the American chemical society 1990,112(6),2457-2458]. Carbohydrate oxidation and oxidative degradation with or without iron catalysts has received much attention, particularly in the degradation of functionalized starch and cellulose and wood polysaccharides [ Emery, J.A. et al, Woodscience and Technology 1974,8(2), 123-; xu, g.; goodell, b., Journal of biotechnology 2001,87(1), 43-57; haskins, j.f.; hogsed, m.j., The Journal of organic Chemistry 1950,15(6), 1264-;
Recently, the fenton system has been used for the depolymerization of chondroitin sulfate, heparin, and other glycosaminoglycans [ Achour, o. et al, Carbohydrate Polymers 2013,97(2), 684-; li, j. -h, et al, Marine Drugs 2016,14(9), 170; petit, a.c., et al, Carbohydrate Polymers 2006,64(4), 597-; wu, M. et al, Carbohydrate Polymers 2010,80(4),1116-1124 ]. All of these documents use acid-containing substrates in the form of iduronic or glucuronic acid residues.
Summary of The Invention
Methods of forming oligosaccharides from polysaccharides are provided. In some embodiments, the method comprises reacting a polysaccharide with hydrogen peroxide and Fe3+、Fe2+、Cu2+Or other metal as described herein, and then cleaving the glycosidic linkages in the polysaccharide with a base to produce an oligosaccharide from the polysaccharide. This reaction is referred to herein as "FITDOG".
We have developed a method for producing bioactive oligosaccharides by digesting polysaccharides from plants, bacteria and yeast. The method uses iron (Fe)3+,Fe2+) Or other transition metals (including but not limited to Cu)1+,Co2+Etc.) and hydrogen peroxide. In some embodiments, the oligosaccharides produced are in the DP3-20 range (DP means degree of polymerization). In some embodiments, the methods will produce oligosaccharides for analysis and bioactive foods, such as prebiotic, anti-cancer, pathogen-blocking, or foods with other functions.
The method can be used to convert polysaccharides (e.g., from plants, bacteria, or yeast) into bioactive oligosaccharides. The method involves reacting a polysaccharide with Fe3+And hydrogen peroxide. Other metal ions, including but not limited to Fe2+And Cu2+The same results can be produced with different potencies. In some embodiments, the reaction is allowed to proceed for 30 minutes (or, e.g., 10 minutes to 4 hours, e.g., 15 minutes to 2 hours, or 10 minutes to 1 hour). The reaction is then quenched with a base (e.g., aqueous sodium hydroxide, calcium hydroxide, potassium hydroxide, etc.).
In some embodiments, the properties of the resulting oligosaccharides can be determined. In some embodiments, high performance liquid chromatography-mass spectrometry (LC-MS) analysis of the product mixture reveals numerous oligosaccharide structures, ranging in size from a degree of polymerization of 3 to 20 (or, e.g., 3-200), depending on the polysaccharide source. Oligosaccharide structure and composition depend on the polysaccharide source.
In some embodiments, there is provided the production of plant-derived oligosaccharides consisting of a Degree of Polymerization (DP) of 3 to 20 (or, e.g., 3 to 200). Polysaccharides may include, for example, those obtained from known food sources, such as rice, banana, squash (squash), wheat flour, and polysaccharides as byproducts of food production. In some embodiments, the polysaccharides can be from waste food products and sources not commonly recognized as food. In some embodiments, the polysaccharide source is a processed food or a plant product.
In some embodiments, the method provides for the production of oligosaccharides (e.g., oligosaccharides with a degree of polymerization of DP3-20 (or e.g., 3-200)) from bacterial cell wall polysaccharides.
In some embodiments, the method provides for the production of oligosaccharides (e.g., oligosaccharides with a degree of polymerization of DP3 to 20 (or, e.g., 3 to 200)) from yeast murein.
In some embodiments, the method provides for the production of oligosaccharides (e.g., oligosaccharides with a degree of polymerization of DP3-20 (or e.g., 3-200)) from algal polysaccharides.
In some embodiments, the oligosaccharide is a bioactive oligosaccharide. In some embodiments, the bioactive oligosaccharide is consumed by bacteria beneficial to the human gut. In some embodiments, the bioactive oligosaccharide modulates the immune system. Oligosaccharides can cause the immune system to respond insufficiently or excessively to known or unknown stimuli. In some embodiments, the bioactive oligosaccharide acts to block a pathogen.
In some embodiments, the oligosaccharide is a selective carbon substrate for stimulating the growth of a soil microbiota. In some embodiments, the oligosaccharides are added to the soil after fumigation or disinfection of the soil. If left uncontrolled, accessible organic carbon drives soil ecology toward pathogens. By providing specific oligosaccharides that selectively stimulate the growth of beneficial soil microflora, the soil pathogen community in the soil can be reduced. In some embodiments, a combination of one or more oligosaccharides prepared as described herein can be added to soil containing one or more microorganisms (e.g., beneficial soil microorganisms).
In some embodiments, one or more oligosaccharides prepared as described herein can be used to produce prebiotics for use in food supplements. In some embodiments, the oligosaccharides may be used for appetite control and/or energy (calorie) intake in overweight and obese children.
In some embodiments, methods of producing soluble fiber from insoluble fiber comprising polysaccharide using reaction conditions described herein are provided. By running the reaction only to a certain extent, it is possible to produce a composition (e.g. gel or ointment) with the desired properties. The soluble fiber products are useful for a number of purposes including, but not limited to, medical products and devices, food products (i.e., thickeners, nutritional improvers, flavor modifiers), soil amendments (for enriching specific beneficial soil microbiome components), and fiber production (i.e., novel fabrics, ropes, biodegradable packaging, etc.). In some embodiments, for example, the insoluble fiber is cotton.
In some embodiments, methods of producing oligosaccharides from polysaccharides are provided. In some embodiments, the method comprises reacting a polysaccharide in a reaction mixture with hydrogen peroxide and a transition metal or an alkaline earth metal; the reaction is then quenched with base and/or the glycosidic linkages in the polysaccharide are cleaved with base, thereby producing a mixture of oligosaccharides from the polysaccharide. In some embodiments, the reaction mixture comprises a transition metal. In some embodiments, the transition metal is selected from iron (e.g., Fe3+, Fe2+), copper (e.g., Cu2+), manganese, cobalt, or molybdenum. In some embodiments, the reaction mixture comprises an alkaline earth metal. In some embodiments, the alkaline earth metal is selected from calcium or magnesium.
In some embodiments, the concentration of transition metal or alkaline earth metal in the reaction mixture is at least 0.65 nM. in some embodiments, the concentration of transition metal or alkaline earth metal in the reaction mixture is from 0.65nM to 500 nM. in some embodiments, the concentration of hydrogen peroxide in the reaction mixture is at least 0.02M in some embodiments, the concentration of hydrogen peroxide in the reaction mixture is 0.02M-1M in some embodiments, the base is sodium hydroxide, potassium hydroxide, or calcium hydroxide in some embodiments, the base concentration is at least 0.1M in some embodiments, the base concentration is 0.1M-5.0M in some embodiments, the polysaccharide comprises one or more of amylose, amylopectin (amylopectic), β -glucan, amylopectin (Pullulan), xyloglucan, arabinogalactan I and arabinogalactan il II, polygalactouronic acid I, polygalactogalacturonic acid II, rhamnogalactan II, galactan arabinogalactan, a polysaccharide from a source of rosewood, a source of a plant, a source of a polysaccharide from a source of a plant, such as a rhamnogalactan oligosaccharide, a source of a plant, a source of a plant, such as a source of a plant.
In some embodiments, prior to the reacting, the method comprises contacting the polysaccharide with one or more polysaccharide-degrading enzymes. In some embodiments, the one or more polysaccharide degrading enzymes comprise amylase, isoamylase, cellulase, maltase, polyglucoside or a combination thereof.
Also provided are compositions comprising the oligosaccharide mixtures produced by the methods described above or elsewhere herein or purified one or more oligosaccharides produced by the methods described above or elsewhere herein.
Also provided are oligosaccharides from table 1 or a mixture of two or more oligosaccharides from table 1.
Methods of stimulating microorganisms in vivo or in vitro are also provided. In some embodiments, the method comprises contacting a microorganism (e.g., bacteria, fungi, yeast) and a composition comprising a mixture of oligosaccharides produced by a method described above or elsewhere herein (e.g., table 1) or oligosaccharides in a table under conditions that selectively stimulate the growth of the microorganism. In some embodiments, the microorganism is a prebiotic microorganism. In some embodiments, the microorganism is in the intestinal tract of an animal and the composition is administered to the animal. In some embodiments, the prebiotic microorganism is administered to the animal independently of or with the composition. In some embodiments, the probiotic microorganism is Bifidobacterium pseudocatenulatum (Bifidobacterium pseudocatenulatum). In some embodiments, the microorganism is a soil microorganism, an oral microorganism (e.g., a bacterium), or a skin microorganism (e.g., a bacterium).
Definition of
The "degree of polymerization" or "DP" of an oligosaccharide refers to the total number of saccharide monomer units that are part of a particular oligosaccharide. For example, tetragalactan-oligosaccharides have a DP of 4, with 3 galactose moieties and one glucose moiety.
The term "bifidobacterium" and its synonyms refer to an anaerobic bacterium which has benefits in humans. Bifidobacteria are one of the major bacterial strains that make up the intestinal flora, residing in the gastrointestinal tract, with health benefits to their host. See, for example, Guarner F and Malagelada JR.Lancet (2003)361,512-519 for further description of bifidobacteria in normal gut flora.
"prebiotics" or "prebiotic nutrients" are generally non-digestible food ingredients that, when ingested, beneficially affect the host by selectively stimulating the growth and/or activity of one or a limited number of microorganisms in the gastrointestinal tract. The term "prebiotic" as used herein refers to a non-digestible food ingredient as defined above in a non-naturally occurring state (e.g. purified, chemically or enzymatically synthesized, as opposed to, for example, in whole human milk).
"prebiotic" refers to a living microorganism that when administered in appropriate amounts imparts a health benefit to the host.
As used herein, the terms "about" or "approximately" index value, when used to modify a quantitative value or range-defining amount, and relatively reasonable deviations, such as ± 20%, ± 10%, or ± 5%, known to those skilled in the art are within the meaning of the stated value.
Brief description of the drawings
FIG. 1. exemplary MALDI-MS of FITDOG-produced xyloglucan oligosaccharides.
FIG. 2 iron (III) sulfate concentration was optimized for optimal oligosaccharide abundance.
Figure 3 buffer pH was optimized to obtain optimal oligosaccharide abundance.
Figure 4. optimization of NaOH and hydrogen peroxide concentrations.
FIG. 5. optimization of time and temperature conditions.
FIG. 6Using CuCl2、FeSO4And Fe3(SO4)2HPLC-MS spectra of the resulting oligosaccharides from green pea (green split pea).
Figure 7 relevant monosaccharide composition of foods subjected to FITDOG treatment.
FIG. 8 is a labeled base peak chromatogram of banana peels, chickpeas and millet subjected to FITDOG treatment. The labels correspond to the compounds named in table 1.
FIG. 9 growth of Bifidobacterium pseudocatenulatum MP80 on oligosaccharides produced by Fenton oxidation of Juglans regia.
Figure 10 shows the xylan annotated base peak chromatogram.
Figure 11 shows the base peak chromatogram for arabinoxylan labeling.
Figure 12 shows the annotated base peak chromatogram for lichenan.
Fig. 13 shows a galactomannan labeled base peak chromatogram.
Figure 14 shows a chromatogram of the labeled base peaks of the gum starch.
FIG. 15 shows the base peak chromatogram for the amylose annotation.
FIG. 16 shows a chromatogram of the labeled base peaks of rhamnogalacturonan I.
Figure 17 shows a xyloglucan-annotated base peak chromatogram.
FIG. 18 shows a chromatogram of the labeled base peaks of the thermogelling glycans.
Fig. 19 shows the galactan labeled base peak chromatogram.
Fig. 20 shows the mannan labeled base peak chromatogram.
FIG. 21 shows a chromatogram of the base peak labeled with glucose mannan.
FIG. 22 shows a chromatogram of the labeled base peaks of larch arabinogalactans.
FIG. 23 shows a chromatogram of the noted base peaks of polygalacturonic acid.
Figure 24 shows the base peak chromatogram for inulin labeling.
FIG. 25 shows annotated base peak chromatograms of amylose, where different metals were used in the FITDOG process.
FIG. 26 shows annotated base peak chromatograms of amylose, where different metals were used in the FITDOG process.
FIG. 27 shows an amylose annotated base peak chromatogram.
FIG. 28 shows an annotated base peak chromatogram of yeast cell wall polysaccharide.
FIG. 29 shows an annotated base peak chromatogram of a walnut pumpkin subjected to increasing scale FITDOG showing the degree of polymerization of 1-200+ hexasaccharide. The data were analyzed on a biochip-HPLC/Q-TOF mass spectrometer. The degree of polymerization of the hexasaccharides from 4 to 7 shows the maximum abundance.
Detailed Description
Fenton-type priming (FITDOGOG) to specific oligosaccharide Groups is a method for the controlled degradation of polysaccharides into oligosaccharides. In some embodiments, the crude polysaccharide is first subjected to an induced oxidation treatment of hydrogen oxide and a transition metal or alkaline earth metal (e.g., iron (III) sulfate) catalyst, making the glycosidic bond less stable. Then, alkali-induced cleavage is performed with NaOH or other bases to obtain various oligosaccharides. Neutralization is immediately performed to reduce exfoliation reaction (peeling reaction). The method can produce large amount of bioactive oligosaccharide from various carbohydrate sources.
If desired, the polysaccharide may optionally be treated with one or more polysaccharide degrading enzymes to reduce the average size or complexity of the polysaccharide, and the resulting polysaccharide is then treated with an oxidative treatment and a metal catalyst. Non-limiting examples of polysaccharidases include, for example, amylases, isoamylases, maltases, glucanases, or combinations thereof.
The initial oxidation treatment may include hydrogen peroxide and transition metals or alkaline earth metals, metals of different oxidation states, sizes, groups of the periodic table of elements, and coordination numbers have been tested to understand the application of the FITOC process Each different metal shows activity in the FITTOG reaction although these metals are available for any polysaccharide, oligosaccharides with a predominant degree of polymerization can be produced with different metals.
In some embodiments, the resulting oligosaccharide mixture produced by the process may have an average degree of polymerization of from 2 to 200, for example between 2 and 100 or 3 and 20 or 5 and 50.
The resulting oligosaccharide mixture produced by this process may have a variety of uses. In some embodiments, the oligosaccharide mixture may be used as a prebiotic to selectively stimulate the growth of one or more probiotics. In some embodiments, the oligosaccharide composition may be administered as a prebiotic formulation (i.e., without bacteria) or as a prebiotic formulation (i.e., comprising a desired bacteria such as a bifidobacterium as described herein). In general, the formulation of the composition comprising prebiotic and prebiotic oligosaccharide may be prepared from any food or beverage that is ingestible by humans or animals. Exemplary foods include those of semi-liquid consistency that allow for easy and uniform dispersion of the prebiotic and prebiotic compositions described herein. However, other consistencies (e.g., powder, liquid, etc.) may be used without limitation. Thus, these food products include, but are not limited to, dairy-based products such as cheese, country cheese, yogurt and ice cream. Processed fruits and vegetables, including those for infants, such as applesauce or dehydrated beans and carrots are also suitable for use in combination with the oligosaccharides of the present invention. Infant rice flour such as rice or oat based rice flour and adult cereals such as Musilix (mousse) are also suitable for use in combination with oligosaccharides. In addition to foods intended for human consumption, animal feed may also be supplemented with compositions containing prebiotic and prebiotic oligosaccharides.
Alternatively, the composition containing prebiotic and prebiotic oligosaccharide can be used to supplement beverages. Examples of such beverages include, but are not limited to, infant formulas, toddler formulas, baby drinks, milk, fermented milk, fruit juices, fruit-based beverages, and sports drinks. Many infant and toddler formulations are known in the art and are commercially available, including, for example, Carnation GoodStart (Nestle Nutrition, Glendale, Calif.) and Nutrish A/B produced by Mayfield milk (Athens, Tennessee). Other examples of infant or baby preparations include those disclosed in U.S. patent No. 5,902,617. Other beneficial agents of the composition include supplements to animal milk, such as cow's milk.
Alternatively, the composition comprising prebiotic and prebiotic oligosaccharide may be formulated as a pill or tablet, or encapsulated in a capsule, such as a gelatin capsule. Tablet forms may optionally include, for example, one or more of lactose, sucrose, mannitol, sorbitol, calcium phosphate, corn starch, potato starch, microcrystalline cellulose, gelatin, colloidal silicon dioxide, talc, magnesium stearate, stearic acid, and other excipients, colorants, fillers, binders, diluents, buffering agents, wetting agents, preservatives, flavoring agents, dyes, disintegrants, and pharmaceutically compatible carriers. Cachets or candy forms can include flavored compositions such as sucrose containing in addition to the active ingredient a carrier known in the art, as well as pastilles comprising the composition in an inert base such as gelatin and glycerin or sucrose and acacia emulsions, gels, and the like. The formulation containing prebiotic or prebiotic oligosaccharide may also contain conventional food supplement fillers and bulking agents such as rice flour.
For example, in some embodiments, the composition comprises bovine (or other non-human) milk protein, soy protein, rice protein, β -lactoglobulin, whey, soybean oil, or starch.
The dosage of the composition comprising prebiotic and prebiotic oligosaccharide will vary according to the individual need and will take into account factors such as age (infant versus adult), weight, cause of loss of beneficial gut bacteria (e.g. antibiotic treatment, chemotherapy, disease or age) and the like. According to the present description, the amount administered to the individual should be sufficient to establish colonies of beneficial bacteria in the intestinal tract over time. Size of the doseIt may also be determined by the presence, nature and extent of any adverse side effects that accompany the administration of a composition comprising prebiotic or prebiotic oligosaccharide. In some embodiments, the dosage range is effective as a food supplement for reconstituting beneficial bacteria in the intestinal tract. In some embodiments, the dose of the oligosaccharide composition of the invention ranges from about 1 microgram/L to about 25 grams/L of oligosaccharide. In some embodiments, the dose of the oligosaccharide composition of the invention ranges from about 100 micrograms/L to about 15 grams/L of oligosaccharide. In some embodiments, the dosage of the oligosaccharide composition of the invention ranges from about 1 g/L to about 10 g/L of oligosaccharide. Exemplary bifidobacteria dosages include, but are not limited to, about 10 per dose4To 1012Colony Forming Units (CFU). Another advantageous dosage is about 106To 1010CFU。
The formulation containing prebiotic or prebiotic oligosaccharide may be administered to any individual in need thereof. In some embodiments, the subject is an infant or a toddler. For example, in some embodiments, the individual is less than, e.g., 3 months, 6 months, 9 months, 1 year, 2 years, or 3 years old. In some embodiments, the individual is between 3-18 years of age. In some embodiments, the individual is an adult (e.g., 18 years of age or older). In some embodiments, the individual is over 50, 55, 60, 65, 70, or 75 years of age. In some embodiments, the individual has an immunodeficiency (e.g., an individual with AIDS or undergoing chemotherapy).
Exemplary bifidobacteria useful in the prebiotic compositions of the present invention include, but are not limited to: bifidobacterium longum subspecies Bifidobacterium infantis (Bifidobacterium longum subsp. infantis), Bifidobacterium longum subspecies Bifidobacterium longum (b.longum subsp. longum), Bifidobacterium breve (Bifidobacterium breve), Bifidobacterium adolescentis (Bifidobacterium adolescentis) and Bifidobacterium pseudocatenulatum (b.pseudocatenulatum). The bifidobacteria employed will depend in part on the intended consumer.
It will be appreciated that for some applications it may be advantageous to include other bifidus factors in the formulations described herein. These additional ingredients may include, but are not limited to, fructooligosaccharides such as Raftilose (Rhone-Poulenc corporation, Cranbury, new jersey), inulin (Imperial Holly corporation, Sugar Land, texas), and Nutraflora (golden technologies corporation, Westminister, colorado), as well as lactose, xylo-oligosaccharides, soy-oligosaccharides, lactulose/lactitol, and galacto-oligosaccharides, among others. In some applications, other beneficial bacteria such as Lactobacillus (Lactobacillus), ruminococcus (ruminococcus), Akkermansia (Akkermansia), Bacteroides (Bacteroides), coprobacterium (Faecalibacterium) may be included in the formulation.
The oligosaccharides described herein can be used to stimulate any kind of microorganism. Examples of microorganisms that can be stimulated by oligosaccharides include, for example, soil microorganisms (e.g., mycorrhizal fungi and bacteria and microorganisms used as soil inoculants, such as azospirillum sp.), oral bacteria (e.g., Streptococcus mutans (Streptococcus mutans), Streptococcus gordonii (Streptococcus gordonii), Streptococcus sanguis (Streptococcus sanguinis) and Streptococcus oralis (s.oralis)) and skin bacteria (e.g., Propionibacterium acnes) and ammonia oxidizing bacteria, including, but not limited to, Nitrosomonas (nitrosomas), Nitrosococcus (nitrococcus), spirochete (nitrosopspira), Nitrosomonas (nitrosorovsis), Nitrosomonas (nitrosorocvsis), nitrosophyllum (nitrosorolos) and vibrio nitrosata.
In some embodiments, the oligosaccharide composition is administered to a human or animal in need thereof. For example, in some embodiments, the oligosaccharide composition is administered to a human or animal with at least one of the following symptoms: inflammatory bowel disease syndrome, constipation, diarrhea, colitis, Crohn's disease, colon cancer, Functional Bowel Disorder (FBD), Irritable Bowel Syndrome (IBS), excess sulfate reducing bacteria, Inflammatory Bowel Disease (IBD), and ulcerative colitis. Irritable Bowel Syndrome (IBS) is characterized by abdominal pain and discomfort, flatulence, and altered bowel function, constipation and/or diarrhea. There are three types of IBS: constipation-predominant IBS (C-IBS), alternating IBS (A-IBS) and diarrhea-predominant IBS (D-IBS). The oligosaccharide compositions are useful, for example, for inhibiting or prolonging the recurrence cycle in ulcer patients. The oligosaccharide composition may be administered to treat or prevent any form of functional bowel disorder, particularly Irritable Bowel Syndrome (IBS), such as constipation-type IBS (C-IBS), alternating IBS (A-IBS) and diarrhea-type IBS (D-IBS); functional constipation and functional diarrhea. FBD is a generic term for some chronic or semi-chronic gastrointestinal disorders, which combine intestinal pain, intestinal dysfunction and social confusion.
In other embodiments, the oligosaccharide composition is administered to a subject in need of immune system stimulation and/or for promoting resistance to bacterial or yeast (e.g., Candidiasis (Candidiasis)) infection or sulfate reducing bacteria-induced disease.
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