CN116211886A - Application of chondroitin sulfate and salts thereof in targeted regulation of intestinal flora and metabolites - Google Patents

Abstract

The invention discloses application of chondroitin sulfate and salts thereof in targeted regulation of intestinal flora and metabolites, and belongs to the field of prebiotics. The invention proves the influence of chondroitin sulfate and/or salts thereof on the contents of L-tyrosine and tridecanoic acid in flora metabolites, and shows that CS has the capability of targeted regulation of flora and L-tyrosine and tridecanoic acid in flora metabolites, increases the contents of L-tyrosine and tridecanoic acid in intestinal flora metabolites, is beneficial to maintaining the complete barrier function of intestinal mucosa and relieving inflammation and related inflammatory diseases.

Description

Application of chondroitin sulfate and salts thereof in targeted regulation of intestinal flora and metabolites

Technical Field

The invention relates to application of chondroitin sulfate and salts thereof in targeted regulation of intestinal flora and metabolites, and belongs to the field of prebiotics.

Background

Intestinal flora refers to a population of microorganisms present at the intestinal site. The intestinal flora includes luminal microorganisms and microorganisms that adhere to mucous or mucus layers. In healthy humans, the intestinal flora is in an overall state of equilibrium. In this ecological balance, the microorganisms on the lumen or mucosa play a role, but the microorganisms adhered to the mucosa are considered to play a more important role. The adhesion microorganism colonizes the intestinal tract and can continuously and stably play a role. The normal flora composition of the human intestinal tract is very complex, up to 1000 bacterial types, about 10 ¹⁴ And is 10 times of the number of the cells of the human body. At the same time, the composition of the intestinal flora is often affected by other factors, such as age, sex, stress, dietary factors, especially antibiotic treatment, and thus shows individual differences. In addition, a great deal of researches show that the microecological preparation such as probiotics, prebiotics, synbiotics and the like can regulate and maintain the microecological balance of the host through the actions of biological barrier, adhesion, field planting and the like, thereby improving the health state of the host. Prebiotics refer to a class of nondigestible food ingredients that are selectively utilized by host microorganisms and impart health benefits. Prebiotics are decomposed and absorbed by beneficial bacteria in the intestinal tract, short chain fatty acids, long chain fatty acids and various beneficial amino acids such as tyrosine and the like generated by metabolism, and the beneficial substance metabolites can influence the intestinal barrier and regulate the intestinal-brain axis, have various biological activities and improve the health of a host by generating specific physiological effects. Tridecanoic acid belongs to long-chain fatty acid, and research shows that pectin polysaccharide extracted from ficus pumila can improve the glycolipid metabolic disorder of mice by remodelling intestinal flora, reverse the reduction of the long-chain fatty acid content caused by high-fat diet feeding, and simultaneously the increase of the long-chain fatty acid content further regulates the blood lipid index. In addition, long chain fatty acids produced by metabolism of probiotics can effectively relieve and treat intestinal inflammation by activating peroxisome proliferator-activated receptor (pparγ), and studies have demonstrated that fructooligosaccharides in miceThe anti-inflammatory effect is associated with an increase in the concentration of long chain fatty acids in the colon. Tyrosine is a precursor substance of dopamine, is an important nutritional essential amino acid, and plays an important role in metabolism, growth and development of a host. It has the main effects of preventing and treating hyperthyroidism, stimulating appetite, regulating the host nervous system, improving sleep quality and protecting nerves. Probiotics have been reported to alleviate depression, and their mechanism of action is to alleviate disease symptoms by increasing tyrosine content.

Recent studies have shown that the presence of some potential prebiotics can improve the survival and colonization of next generation probiotics by increasing the antioxidant capacity and resistance to digestive fluids. The current prebiotics are mainly host non-digestible carbohydrates including oligosaccharides, microalgae, polysaccharides, etc. The most widely used fructooligosaccharides and galactooligosaccharides have been shown to increase the abundance of bifidobacteria in the intestinal microbiota and a variety of plant heteropolysaccharides have also shown excellent probiotic properties.

Chondroitin Sulfate (CS) is an acidic mucopolysaccharide, which is a macromolecular polysaccharide formed by alternately connecting disaccharide units formed by glucuronic acid and aminohexose, and is widely distributed in animal and human cartilage, such as animal laryngeal bones, nasal bones, cartilage, myomembranes, vascular walls and the like. Chondroitin sulfate various isomers, according to the sulfuric acid group in amino hexose in different positions, can be divided into chondroitin sulfate A (disaccharide unit: →4GlcAβ1,3GalNAc4Sβ1 →), chondroitin sulfate B (disaccharide unit: →4IdoAα1,3GalNAc4Sβ1 →.), chondroitin sulfate C (disaccharide unit →4GlcAβ1,3GalNAc6Sβ1 →), chondroitin sulfate D (disaccharide unit →4GlcA2Sβ1,3GalNAc6Sβ1 →), etc. Studies show that chondroitin sulfate has the effect of regulating intestinal flora, liu and the like supplement chondroitin sulfate disaccharide to healthy mice and mice subjected to exhaustion exercise stress, and serum indexes, the intestinal flora and the content of short-chain fatty acids of the mice are measured, so that the results show that the chondroitin sulfate disaccharide can relieve intestinal inflammation caused by pressure, improve the reduction of butyric acid content in feces caused by emergency and remarkably promote the growth of Bactoid. However, this article focuses only on bacteroides species and does not analyze differential metabolites, lacking a deep analysis of the correlations between chondroitin sulfate, intestinal flora and flora metabolites. Dan Deling human feces in vitro anaerobic fermentation is carried out on sea cucumber sulfated polysaccharides, degradation and utilization of human intestinal microorganisms on fucosyl chondroitin sulfate and fucosan sulfate with different molecular weights are studied, and researches show that the intestinal microorganisms have lower utilization rate on sea cucumber sulfated polysaccharides and smaller influence on colony composition and structure, but the Parabalerosoidess distastosonis and the Bactoid are obviously increased. However, the article is mainly focused on discussing the influence of sea cucumber sulfated polysaccharides on the structure of intestinal flora, lacks related analysis on flora metabolites, and has a certain limitation on deep analysis of the relationship between sea cucumber sulfated polysaccharides and intestinal flora.

Regulating the levels of L-tyrosine and tridecanoic acid in the intestinal flora metabolites has beneficial effects on regulating the intestinal flora, alleviating inflammation and related inflammatory diseases, but no substances capable of targeted regulation of the levels of L-tyrosine and tridecanoic acid in the intestinal flora metabolites have been found.

Disclosure of Invention

The invention provides application of chondroitin sulfate and/or salts thereof in targeted regulation of L-tyrosine and tridecanoic acid content in intestinal flora and flora metabolites. The intestinal flora can better utilize CS, promote the increase of beneficial bacteria, and achieve the effect of targeted regulation of the L-tyrosine and tridecanoic acid content in flora metabolites by targeted regulation of the abundance of specific bacteroides and bifidobacteria, so as to maintain intestinal homeostasis.

In one embodiment of the present invention, said targeting said regulating human intestinal flora metabolites means increasing the content of L-tyrosine and tridecanoic acid in the human intestinal tract.

In one embodiment of the present invention, the chondroitin sulfate salt may be a sodium salt, a potassium salt, a magnesium salt, a calcium salt, a zinc salt, a bismuth salt of chondroitin sulfate, or a combination of two or more thereof.

In one embodiment of the invention, the targeted modulation of gut flora metabolites is by increasing bacteroides Bacteroidesovatus, bacteroidesthetaiotaomicron, bacteroidescaccae and bacteroides knordii in gut microorganisms; and bifidobacterium Bifidobacteriumadolescentis, bifidobacteriumbifidum, bifidobacteriumlongum and bifidobacteria pseudobulb.

The invention discloses application of chondroitin sulfate and/or a salt thereof in preparing an L-tyrosine and tridecanoic acid intestinal supplement, wherein the chondroitin sulfate salt is sodium salt, potassium salt, magnesium salt, calcium salt, zinc salt, bismuth salt or a combination of two or more of the chondroitin sulfate.

In one embodiment of the invention, the use is by increasing bacteroides Bacteroides ovatus, bacteroidesthetaiotaomicron, bacteroidescaccae and bacteroides snordii in intestinal microorganisms; and the content of bifidobacteria Bifidobacteriumadolescentis, bifidobacteriumbifidum, bifidobacteriumlongum and Bifidobacterium pseudocatenulatum.

In one embodiment of the invention, the intestinal supplements include pharmaceutical products, food products and health products.

In one embodiment of the invention, the food product comprises a solid beverage, a prebiotic jelly; the health product comprises oral liquid.

The invention also provides application of the chondroitin sulfate and/or the salt thereof in preparing a product for regulating intestinal flora, wherein the chondroitin sulfate salt is sodium salt, potassium salt, magnesium salt, calcium salt, zinc salt, bismuth salt or a combination of two or more of the chondroitin sulfate.

In one embodiment of the invention, the modulating the intestinal flora is increasing bacteroides Bacteroides ovatus, bacteroidesthetaiotaomicron, bacteroidescaccae and bacteroides knordii in the intestinal microorganism; and the content of bifidobacteria Bifidobacteriumadolescentis, bifidobacteriumbifidum, bifidobacteriumlongum and Bifidobacterium pseudocatenulatum.

In one embodiment of the invention, the product comprises: medicine, food and health product. Chondroitin sulfate and/or its salt can be used alone or as additive in common food, health product, functional food, special medical food and medicine, wherein the food comprises solid beverage and prebiotic soft candy; the health product comprises oral liquid.

Further, chondroitin sulfate can promote the growth of Bacteroidesspp, bifidobacteriumspp and inhibit the growth of Escherichia-Shigella spp.

The beneficial effects are that:

the invention proves the influence of chondroitin sulfate and/or salts thereof on the contents of L-tyrosine and tridecanoic acid in flora metabolites, and shows that CS has the capability of targeted regulation of the bacteroides and bifidobacteria of the flora and the L-tyrosine and tridecanoic acid in the flora metabolites, increases the contents of the L-tyrosine and the tridecanoic acid in the flora metabolites of the intestinal tract, is beneficial to maintaining the barrier function of the mucous membrane of the intestinal tract to be complete and relieves inflammation and related inflammatory diseases.

Drawings

FIG. 1 polysaccharide content and OD of fermentation broth at various fermentation time points ₆₀₀ Value change: (A) polysaccharide content; (B) OD (optical density) ₆₀₀ 。

FIG. 2 changes in Short Chain Fatty Acid (SCFAs) concentration of fermentation broth at various fermentation time points: (A) acetic acid content; (B) propionic acid content; (C) butyric acid content; (D) isobutyric acid content.

FIG. 3 microbiological taxonomic analysis of fermentation broths at the genus level. 1 and 2 represent Blank and CS groups, respectively, 12, 24, 48 represent different time points, a, B, C, D, E, F represent 6 replicates of samples at different time points, respectively.

FIG. 4 relative abundance of Bacteroides, bifidobacterium and E.coli-Shigella in fermentation broth: (A) Bacteroides genus; (B) bifidobacterium; (C) Escherichia coli-Shigella.

FIG. 5 beta diversity NMDS analysis of fermentation broths. 1 and 2 represent Blank and CS groups, respectively, 12, 24, 48 represent different time points, a, B, C, D, E, F represent 6 replicates of samples at different time points, respectively.

FIG. 6 abundance of bacteroides species in fermentation broth: (A) Bactoid messages; (B) Bactoidesvul gap; (C) Bactoidesfragils; (D) bacterioidesfinediol; (E) bacteriodes stataiotamicin; (F) Bacteroides stercori; (G) Bactoidesxylanisavens; (H) Bactoidesu formis; (I) bacterioidescacce; (J) Bactoidesintestinellinalis; (K) Bactoidesnordii; (L) Bactoid sporebeius.

FIG. 7 abundance of bifidobacteria species in fermentation broth: (A) Bifidobacterium adoleracentis; (B) Bifidobacterium bifidum; (C) Bifidobacterium longum; (D) Bifidobacterium pseudobulb.

FIG. 8 is a score plot of analysis of the metabolite OPLS-DA in the fermentation broth.

FIG. 9 differential metabolite analysis in fermentation broths of CS group and blank group.

FIG. 10 correlation analysis of CS-mediated differential metabolites with Bacteroides species.

FIG. 11 correlation analysis of CS-mediated differential metabolites with bifidobacteria species.

Detailed Description

The present invention will be described in further detail by the following examples, which are only for the purpose of illustrating the present invention and are not to be construed as limiting the scope of the present invention.

The following experimental examples relate to the following media:

improved GMM liquid medium: 10.0g of peptone, 5.0g of yeast extract, 5.0g of beef extract, 13.61g of anhydrous potassium dihydrogen phosphate, 0.4g of sodium bicarbonate, 0.002g of magnesium sulfate heptahydrate, 0.08g of sodium chloride, 0.5g of cysteine monohydrate, 0.08g of calcium chloride, 0.001g of vitamin K, 0.4mg of ferrous sulfate heptahydrate, 10mg of methemoglobin, 31mg of histidine, 80 2mL of tween, 10mL, ATCCTraceMineralMix mL of ATCCCVitamin, 4mL of resazurin, adding distilled water to 1000mL of resazurin, adding CS5g in addition to a modified GMM liquid medium in a CS group, and adding no CS in a blank control group. Adjusting pH to 7.0-7.2, packaging 10mL culture solution in anaerobic tube, filling nitrogen, sealing with cover, and sterilizing at 121deg.C for 15min.

The reagents used in the invention are all common reagents and can be purchased in conventional reagent production and sale companies.

Example 1: modulation of intestinal flora by chondroitin sulfate

To further investigate the chondroitin sulphate in intestinal flora modulationBy simulating an in-vitro colon fermentation system to research the regulation effect of chondroitin sulfate on fecal flora and detecting OD before and after fermentation ₆₀₀ The values, the polysaccharide content, the short chain fatty acid content, the flora structure, the level abundance of bacteroides and bifidobacteria species, the metabolome and other parameters are verified, so that the effect of chondroitin sulfate on targeted regulation of intestinal flora and metabolome is verified.

1.1 in vitro simulation of colon fermentation

Fresh fecal inoculum from four donors who had not taken any antibiotics or probiotics for at least three months, were healthy (BMI: 18.5-25), and had no digestive tract disease. Faeces from four donors were mixed in equal amounts, diluted with 10mM phosphate buffered saline (PBS, pH 7.4) in a 1:7 ratio, and then thoroughly mixed with a vortex mixer. Then the fecal inoculum is filtered through four layers of sterile medical gauze and immediately transferred to an anaerobic tank for standby.

The experiments were performed in triplicate with a blank and a CS group, with 2mL human fecal suspension inoculated per 10mL of modified GMM liquid medium, anaerobic culture at 37 ℃ for 0, 12, 24, 36, 48 h.

1.2 determination of polysaccharide content

The polysaccharide content was determined using a modified phenol sulfuric acid method. Standard substance solutions with proper series concentrations are prepared, respectively placed in a 10mL colorimetric tube, 1.0mL of 6% phenol solution and 5.0mL of concentrated sulfuric acid are sequentially added, uniformly mixed, and after being placed at room temperature for 30min, the absorbance value is measured at the wavelength of 490 nm. And drawing a standard curve by taking the absorbance value as an ordinate and the standard concentration as an abscissa. The fermentation product was centrifuged (12,000 rpm,10min,4 ℃) and the supernatant was taken, diluted appropriately, developed according to the method described above, and the absorbance was measured, taken into a standard curve, and the polysaccharide content of the sample was calculated.

The utilization of polysaccharides by the intestinal flora is influenced by the structure and composition of the polysaccharides. The change in polysaccharide content in the samples during the fermentation period of 0-48 hours for the feces of the blank and CS groups was measured and is shown in FIG. 1A. Along with the increase of the sample fermentation time, the polysaccharide content in the CS group fermentation liquor is obviously reduced from 0h to 24h, the descending trend after 36h is gradually flattened, and the polysaccharide content of the fermentation liquor at each time point is extremely obviously lower than 0h; the polysaccharide content in the fermentation broth of the blank group has no obvious change in the fermentation process. The results showed that 72.66% of CS had been degraded by the intestinal flora at 24h, indicating that CS could be well utilized by human intestinal microorganisms.

1.3OD ₆₀₀ Is (are) determined by

Collecting fermentation products of blank group and CS group 0, 12, 24, 36, 48 hr respectively, and measuring OD of each sample by using multifunctional enzyme-labeled instrument ₆₀₀ 。

OD of each sample during fermentation ₆₀₀ The variation of (2) is shown in figure 1B. OD of blank control group sample ₆₀₀ The values were in a slowly rising trend from 0h to 36h and in a decreasing trend from 36h to 48 h. OD of CS group sample ₆₀₀ The values increased significantly from 0h to 24h, and decreased in the trend from 24h to 48h, combined with the above polysaccharide content changes, indicating that the degraded CS significantly promoted intestinal microbial growth during fermentation 24 h. OD of CS group ₆₀₀ The time is obviously higher than that of a blank control group in 12-48 hours, which shows that CS can obviously promote the growth of intestinal microorganisms.

1.4 determination of Short Chain Fatty Acids (SCFAs)

Fermentation solutions for fermentation 0, 12, 24 and 48 hours were centrifuged (12,000 rpm,10min,4 ℃) respectively, 0.5mL of the supernatant was sucked, 0.02mL of 10% sulfuric acid was added thereto, shaking was performed for 30 seconds, then 1mL of an ether solution was accurately added thereto in a fume hood, shaking was performed for 30 seconds, and then centrifuged (8000 rpm,15min,4 ℃) to remove the supernatant into a centrifuge tube containing 0.25g of anhydrous sodium sulfate, shaking was uniform, and centrifuged (800 rpm,15min,4 ℃) to obtain the supernatant into a gas sample bottle, and short chain fatty acid content was detected by GC-MS, the detection results being shown in FIG. 2.

SCFAs are the major metabolites in carbohydrate fermentation processes, and their concentration is considered to be an important reflective indicator of gut flora activity. As can be seen from FIG. 2, CS can up-regulate the short chain fatty acid content in the fermentation broth. After 12h fermentation, the contents of acetic acid, propionic acid, butyric acid and isobutyric acid in the fermentation broth of the CS group are all significantly higher than those of the blank group. Wherein acetic acid, propionic acid, butyric acid and isobutyric acid of CS group were 1.41,1.49,1.45 and 1.50 times of the blank group, respectively, after 48 hours of fermentation.

1.5DNA extraction and 16SrRNA Gene sequencing

Fermenting the fermentation liquid for 12, 24 and 48 hours respectively, centrifuging (6000 rpm,10min,4 ℃), removing supernatant, extracting bacterial genome precipitated by sample centrifugation by adopting a FastDNA SpinKitforFeces kit, performing PCR amplification by using a universal primer pair 16sV3-V4 region sequence, and detecting intestinal flora diversity in a fecal sample by a second-generation sequencer. Definition of relative abundance: the lowest level of microorganisms in the column was detected, the percentage of the same type of microorganisms (bacteria/virus/fungi/parasites).

To investigate the regulating effect of CS on the structure of the intestinal flora, the changes in the composition of the fermented sample flora at different time points were analyzed at the genus level. As can be seen from fig. 3, 4A and 4B, the relative abundance of bacteroides and bifidobacteria in the CS fermented samples at each time point was significantly higher than that in the placebo group as the fermentation time was increased, wherein the relative abundance of bacteroides in the 24hCS samples was 3.55 times that in the placebo group (10.2% in the placebo group and 36.1% in the CS group) and 8.12 times that in the placebo group (0.09% in the placebo group and 0.72% in the CS group). In addition, as can be seen from fig. 4C, the relative abundance of escherichia coli-shigella in the CS fermented samples at each time point is significantly lower than that in the blank, and the relative abundance of escherichia coli-shigella in the 24h blank samples is 13.08 times that in the CS samples (13.6% for the blank and 1.0% for the CS). As can be seen from fig. 5, the NMDS analysis can obtain that the structure of the flora of the CS group sample is different from that of the blank group at different time points.

1.6 Bifidobacterium and Bacteroides species level sequencing

The product of fermentation for 24h was centrifuged (6000 rpm,10min,4 ℃) to remove supernatant, and the precipitated bacterial genome obtained by centrifugation of the sample was extracted using a FastDNASpin kit, and then PCR amplification was performed on GroEL region sequences using bifidobacterium-specific primers, respectively, and second generation sequencing was performed after PCR amplification was performed on rpsD region sequences using bacteroides-specific primers.

Bacteroides can participate in a number of important metabolic activities in the human colon and also protect the body to some extent from invasive pathogens. In addition, the bifidobacterium is a physiologically beneficial bacterium and has various important physiological functions of biological barrier, immunity enhancement, gastrointestinal tract function improvement and the like for human health. As can be seen from fig. 6 and 7, the abundance of Bacteroidesovatus, bacteroidesthetaiotaomicron, bacteroidescaccae, bacteroidesnordii, bacteroidesstercoris and bacteroidesplebius in the CS group 24h samples increased significantly compared to the blank group by 1.81,2.31,4.46, 1.70, 4.73 and 34.47 times, respectively; in the aspect of bifidobacterium species, the abundance of Bifidobacteriumadolescentis, bifidobacteriumbifidum, bifidobacteriumlongum, bifidobacteriumpseudocatenulatum is obviously increased by 1.82,1.82,1.56 and 2.63 times respectively. The results show that CS has the potential of targeted regulation of intestinal flora.

1.7 determination of fermentation broth metabolites

0.1mL of the fermentation supernatant was taken, 0.4mL of a mixed solution of methanol and acetonitrile (v: v=1:1, -20 ℃ C. Pre-cooling), vortexing for 30s, sonicating in an ice-water bath for 10min, -20 ℃ C. Incubation for 1h, centrifuging (15000 rpm,15min,4 ℃ C.) and taking the supernatant. The supernatant was evaporated to dryness on a rotary evaporator and 200 μl methanol was added: the water (v: v=4:1) was reconstituted and then centrifuged (15000 rpm,15min,4 ℃), and the supernatant was filtered into an injection bottle with a 0.22 μm filter. Transferring the extracted sample into a liquid phase vial for LC-MS analysis. Sample metabolite results were initially screened and derived using a compounddescoverter.

The results of the obtained sample metabolites were subjected to OPLS-DA analysis, and as apparent from fig. 8, the CS group and the blank group were separated, indicating a significant difference between the metabolites of the two groups. Fig. 9 and table 1 show the differential metabolites between the CS group and the blank group obtained by the screening.

TABLE 1 differential metabolites of fermentation supernatants from CS and blank

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1.8 correlation analysis of differential metabolite levels in Bacteroides and Bifidobacterium species

To determine the correlation between CS-mediated changes in intestinal microbial strains and metabolites, we performed a Spearman correlation analysis. From FIGS. 10 and 11, it can be seen that L-tyrosine and tridecanoic acid in the samples are significantly positively correlated with the abundance of Bactoides and Bifidobacterium. In combination with the above conclusion, CS can promote the growth of specific bacteroides and bifidobacteria in the intestinal flora by regulating the structure of the intestinal flora, thereby increasing the content of L-tyrosine and tridecanoic acid in the metabolites.

From the above, CS has a beneficial effect on the regulation of intestinal flora, and the production of short chain fatty acids. In addition, CS can promote the increase of beneficial bacteria Bifidobacterium and inhibit the growth of escherichia coli-Shigella. In addition, CS can also have certain flora targeting regulation and targeting regulation effects on the L-tyrosine and the tridecanoic acid in flora metabolites by promoting the growth of specific bacteroides and bifidobacteria in intestinal flora, has beneficial effects on the health of hosts and has the potential of relieving inflammation and related inflammatory diseases.

Example 2: preparation of chondroitin sulfate solid beverage

Chondroitin sulfate can be used for preparing a solid beverage, and the weight of each component in the solid beverage is as follows: 0.2 to 0.3 part of chondroitin sulfate, 5 parts of blueberry fruit powder, 15 parts of fructo-oligosaccharide, 15 parts of maltodextrin and 0.1 part of zinc gluconate. The components are prepared into powder by adopting a conventional preparation method, the raw material powder is respectively and accurately weighed, fully and uniformly mixed and packaged.

Example 3: chondroitin sulfate for preparing oral liquid

Chondroitin sulfate can be used for preparing oral liquid, and the weight of each component in the oral liquid is as follows: 0.2 to 0.3 part of chondroitin sulfate, 10 to 20 parts of potassium sorbate, 20 parts of isomaltooligosaccharide, 5 parts of citric acid and 100 parts of purified water. The components are prepared according to parts by weight, are fully dissolved in purified water, and are filtered, sterilized and canned to obtain the finished product.

Example 4: chondroitin sulfate for preparing prebiotic soft sweets

Chondroitin sulfate can be used for preparing the prebiotic soft candy, and the weight of each component of the prebiotic soft candy is as follows: 30 parts of concentrated juice, 0.2-0.3 part of chondroitin sulfate, 1 part of fructo-oligosaccharide, 1 part of isomaltooligosaccharide, 0.5 part of citric acid, 40 parts of white granulated sugar, 1 part of carrageenan and 1.5 parts of pectin. And (5) preparing a mixed gel solution according to a conventional soft sweet preparation method, casting, molding and packaging to obtain a finished product.

While the invention has been described with reference to the preferred embodiments, it is not limited thereto, and various changes and modifications can be made therein by those skilled in the art without departing from the spirit and scope of the invention as defined in the appended claims.

Claims (10)

1. Use of chondroitin sulphate and/or a salt thereof for targeted modulation of the L-tyrosine and tridecanoic acid content in a gut flora metabolite, said targeted modulation being the increase of the L-tyrosine and tridecanoic acid content in the gut flora metabolite, said chondroitin sulphate salt being the sodium, potassium, magnesium, calcium, zinc, bismuth salt of chondroitin sulphate or a combination of two or more thereof.

2. The use according to claim 1, wherein the targeted modulation of gut flora metabolites is by increasing bacteroides Bacteroidesovatus, bacteroidesthetaiotaomicron, bacteroidesplebeius, bacteroidescaccae and bacteroides noddii in gut microorganisms; and bifidobacterium Bifidobacteriumadolescentis, bifidobacteriumbifidum, bifidobacteriumlongum and bifidobacteria pseudobulb.

3. Use of chondroitin sulfate and/or a salt thereof in the preparation of an L-tyrosine and tridecanoic acid intestinal supplement, the chondroitin sulfate salt being a sodium, potassium, magnesium, calcium, zinc, bismuth salt of chondroitin sulfate or a combination of two or more thereof.

4. The use according to claim 3, wherein the use is by increasing bacteroides Bacteroidesovatus, bacteroidesthetaiotaomicron, bacteroidesplebeius, bacteroidescaccae and bacteroides snordii in intestinal microorganisms; and bifidobacterium Bifidobacteriumadolescentis, bifidobacteriumbifidum, bifidobacteriumlongum and bifidobacteria pseudobulb.

5. The use according to claim 3, wherein the intestinal supplements include pharmaceuticals, foods and nutraceuticals.

6. The use according to claim 5, wherein the food product comprises a solid beverage, a prebiotic jelly; the health product comprises oral liquid.

7. Use of chondroitin sulphate and/or a salt thereof for the preparation of a product for modulating the intestinal flora, said salt of chondroitin sulphate being a sodium, potassium, magnesium, calcium, zinc, bismuth salt of chondroitin sulphate or a combination of two or more thereof.

8. The use according to claim 7, wherein the modulation of intestinal flora is the increase of bacteroides Bacteroidesovatus, bacteroidesthetaiotaomicron, bacteroidesplebeius, bacteroidescaccae and bacteroides knordii in intestinal microorganisms; and bifidobacterium Bifidobacteriumadolescentis, bifidobacteriumbifidum, bifidobacteriumlongum and bifidobacteria pseudobulb.

9. The use according to claim 7, wherein the products include medicines, foods and health products, and the chondroitin sulfate and/or its salt can be used alone or as an additive in general foods, health products, functional foods, special medical use foods and medicines.

10. The use according to claim 9, wherein the food product comprises a solid beverage, a prebiotic jelly; the health product comprises oral liquid.

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