CN117384804A - Lactobacillus gasseri B1-26 and application thereof - Google Patents
Lactobacillus gasseri B1-26 and application thereof Download PDFInfo
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- CN117384804A CN117384804A CN202311695608.6A CN202311695608A CN117384804A CN 117384804 A CN117384804 A CN 117384804A CN 202311695608 A CN202311695608 A CN 202311695608A CN 117384804 A CN117384804 A CN 117384804A
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Classifications
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- C—CHEMISTRY; METALLURGY
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- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
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- A—HUMAN NECESSITIES
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- 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
- A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
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- 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
- A61P1/10—Laxatives
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- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
- C12R2001/00—Microorganisms ; Processes using microorganisms
- C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
- C12R2001/225—Lactobacillus
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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Abstract
The invention provides lactobacillus gasseri B1-26 and application thereof, and relates to the technical field of microorganisms. The Lactobacillus gasseri is [ ]Lactobacillus gasseri) The preservation number of B1-26 is CGMCC NO.19749. The strain is derived from human milk, has functions of preventing, relieving and/or treating constipation, and can be used for preparing food, health product or medicine to promote gastrointestinal motility and increase defecation amount.
Description
Technical Field
The invention relates to the technical field of microorganisms, in particular to lactobacillus gasseri B1-26 and application thereof.
Background
Constipation refers to a clinical disease characterized by a reduced number of bowel movements, difficulty in bowel movements, and hard stool, and causes hemorrhoids, anal fissure, proctitis, and the like for a long period of time. Constipation is one of important factors affecting healthy growth of children, and infant constipation seriously causes dysplasia, slow growth and development, and immunity decline and other problems. The medicines for treating constipation clinically mainly comprise a stimulant laxative, a lubricating laxative, a hypertonic laxative and the like, and lack of products suitable for relieving constipation of infants.
The probiotics are planted in human intestinal tracts, and the probiotic characteristics are utilized to regulate the balance of intestinal flora, promote the absorption of nutrient substances by organisms, relieve inflammation, reduce the incidence rate of metabolic diseases and the like, so that the immunity of the organisms is improved. Breast milk is an essential nutrient source for infants in the early growth stage, and plays a vital role in the growth and development of infants. The presence of probiotics in breast milk has been confirmed by a number of studies. Therefore, more probiotics are discovered from the breast milk, so that the probiotics which can be used for infant food can be developed, and the problem of infant constipation is relieved.
In view of this, the present invention has been made.
Disclosure of Invention
The invention aims at providing a lactobacillus gasseri strainLactobacillus gasseri) B1-26, deposit number: CGMCC No.19749, which is derived from human milk and has the function of relieving constipation. Based on the characteristics of the strain, another object of the invention is also to provide products comprising the same and uses thereof.
In order to solve the technical problems, the invention adopts the following technical scheme:
in a first aspect, a strain of Lactobacillus gasseri is providedLactobacillus gasseri) B1-26, deposit number: CGMCC No.19749.
In a second aspect, a microbial inoculum is provided, the microbial inoculum comprises the Lactobacillus gasseri of the first aspectLactobacillus gasseri)B1-26。
In a third aspect, a fermentation process is provided, the fermentation process comprising using a fermentation process comprising a first fermentation processLactobacillus gasseri in aspectLactobacillus gasseri) B1-26 fermenting the substrate with a starter; or fermenting the substrate with a starter comprising the microbial agent of the second aspect.
In a fourth aspect, there is provided the use of lactobacillus gasseri (Lactobacillus gasseri) B1-26 of the first aspect, or the microbial inoculum of the second aspect, or the fermentation process of the third aspect, in the manufacture of a product for the prevention, alleviation and/or treatment of constipation.
In alternative embodiments, the products for preventing, alleviating and/or treating constipation include food, health products and pharmaceutical products.
In alternative embodiments, the food product for preventing, alleviating and/or treating constipation comprises a dairy product.
In alternative embodiments, the methods for preventing, alleviating and/or treating constipation comprise methods for promoting gastrointestinal motility.
In alternative embodiments, the method for preventing, alleviating and/or treating constipation comprises increasing the amount of bowel movement in a subject.
In a fifth aspect, there is also provided a product for preventing, alleviating and/or treating constipation, the product comprising Lactobacillus gasseri according to the first aspectLactobacillus gasseri) B1-26 or the microbial agent of the second aspect; or, prepared by the fermentation method of the third aspect; or, comprising a fermentation product produced by the fermentation process of the third aspect.
In alternative embodiments, products for preventing, alleviating and/or treating constipation include food, health products and pharmaceuticals.
Compared with the prior art, the invention has the following beneficial effects:
the invention provides Lactobacillus gasseriLactobacillus gasseri) B1-26 was isolated from fresh breast milk, which was shown to promote gastrointestinal motility and increase stool output in subjects. The lactobacillus gasseri B1-26 discovered by the invention has potential for developing functional foods, health products and medicines. Lactobacillus gasseri B1-26 or microbial inoculum containing same, or fermentation method using same, and can be used for preparing food, health product or medicine, and contains Lactobacillus gasseri B1-26Or a microbial inoculum containing the same, or a product of a fermentation product thereof, has the function of preventing, relieving and/or treating constipation.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are needed in the description of the embodiments or the prior art will be briefly described, and it is obvious that the drawings in the description below are some embodiments of the present invention, and other drawings can be obtained according to the drawings without inventive effort for a person skilled in the art.
FIG. 1 is a annotation of the NR database of the sequencing results of Lactobacillus gasseri B1-26;
FIG. 2 shows colony morphology of Lactobacillus gasseri B1-26;
FIG. 3 shows the microscopic morphology of Lactobacillus gasseri B1-26;
FIG. 4 shows the results of the intestinal tract propulsion rate experiments of the mice in each experimental group of example 2;
FIG. 5 is a graph showing the results of the statistics of the number of grains of the feces of the mice in each experimental group of example 2;
FIG. 6 shows the results of the fecal weight statistics of mice in each experimental group of example 2.
Detailed Description
The technical solutions of the present invention will be clearly and completely described in connection with the embodiments, and it is apparent that the described embodiments are some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
According to one aspect of the invention, the invention provides a strain of Lactobacillus gasseriLactobacillus gasseri)B1-26。
The preservation date of the strain of the invention is 2020, 04 and 27, and the preservation number is: CGMCC No.19749. The classification is named: lactobacillus gasseri @Lactobacillus gasseri) The accession number is named: china general microbiological culture Collection center, address: north Chen Xili No.1 hospital in the Chaoyang area of Beijing city of ChinaThe institute of microbiology, national academy of sciences 3.
Herein, lactobacillus gasseri @ isLactobacillus gasseri) B1-26 are also described as Lactobacillus gasseri B1-26, B1-26 and Breast milk-derived Lactobacillus gasseri B1-26, and the above-mentioned strain names may be arbitrarily used interchangeably.
The Lactobacillus gasseri B1-26 is separated from human fresh breast milk and contains 1% CaCO 3 After 48 hours of culture in MRS solid culture medium, the strain has obvious transparent rings, round shape, smooth surface and neat edge, and is white or milky white and is gram positive; the 16sRNA is shown as SEQ ID NO. 1; NR (Non-Redundant Protein Database) database annotation was performed on the sequencing result of Lactobacillus gasseri B1-26, 93.61% of the gene Fu Gege Lactobacillus was identified as Lactobacillus gasseri by combining with colony morphologyLactobacillus gasseri). In-vitro experiments prove that the lactobacillus gasseri B1-26 can promote intestinal peristalsis of mice, increase defecation amount of constipation model mice, and has the effect of relieving constipation.
In a second aspect, there is also provided a microbial agent comprising lactobacillus gasseri B1-26 of the first aspect. It can be understood that the microbial inoculum provided by the invention contains the lactobacillus gasseri B1-26, so that the microbial inoculum has all the performances and beneficial effects of the lactobacillus gasseri B1-26. The microbial inoculum preferably takes lactobacillus gasseri B1-26 as a main active ingredient; optionally, the microbial agent may further comprise one or more microorganisms for use in combination with lactobacillus gasseri B1-26, including, but not limited to, one or more of bifidobacterium longum, bifidobacterium breve, bifidobacterium ovale, bifidobacterium thermophilum, lactobacillus plantarum, lactobacillus acidophilus, lactobacillus paracasei, streptococcus thermophilus, lactobacillus bulgaricus, lactobacillus jensenii, lactobacillus raman, bifidobacterium animalis, bifidobacterium lactis, lactobacillus rhamnosus, lactobacillus reuteri, lactobacillus fermentum, lactobacillus helveticus, bifidobacterium infantis, and bifidobacterium bifidum.
In an alternative embodiment, the microbial agent may further include any acceptable auxiliary materials, wherein the acceptable auxiliary materials do not affect the physiological functions of the active ingredients in the microbial agent, and are components with auxiliary effects on the microbial agent, including but not limited to one or more of a pH regulator, an emulsifier, a disintegrating agent, a filler, a solvent, a wetting agent, a stabilizer, a dispersing agent and a humectant; optionally, the auxiliary materials can also comprise nutrients for maintaining the activity of the strains in the microbial inoculum, including, but not limited to, saccharides, salts, yeast extract, beef extract, etc.; optionally, the adjunct may also include a carrier for adsorbing microorganisms including, but not limited to, one or more of montmorillonite, kaolin, white carbon, sepiolite, straw powder, starch, corn flour, polyvinyl alcohol and polyethylene glycol, and light calcium carbonate.
In a third aspect, there is also provided a fermentation process comprising fermenting a substrate with a starter comprising lactobacillus gasseri B1-26 of the first aspect; or fermenting the substrate with a starter comprising the microbial agent of the second aspect.
In alternative embodiments, the fermentation substrate of the fermentation process comprises milk, the sources of which include, but are not limited to, humans, cows, sheep, horses, camels, and the like.
In a fourth aspect, there is also provided the use of lactobacillus gasseri B1-26 of the first aspect, or the microbial inoculum of the second aspect, or the fermentation process of the third aspect, for the manufacture of a product for the prevention, alleviation and/or treatment of constipation. Exemplary products for preventing, alleviating and/or treating constipation include, but are not limited to, food products, nutraceuticals, and pharmaceuticals.
In alternative embodiments, the methods for preventing, alleviating and/or treating constipation comprise promoting gastrointestinal motility. Experiments prove that the Lactobacillus gasseri B1-26 can promote the peristalsis of the constipation model mice after being interfered.
In alternative embodiments, the method for preventing, alleviating and/or treating constipation comprises increasing the amount of bowel movement in the subject. Experiments prove that the fecal particle number and the fecal weight of the constipation model mice can be improved after the intervention of the lactobacillus gasseri B1-26.
In alternative embodiments, the subject of the product for preventing, alleviating and/or treating constipation comprises a mammal including, but not limited to, a human, pig, cow, horse, monkey, rat, mouse, guinea pig, sheep or goat. The subject may be a constipation patient, or may be an animal model with constipation symptoms obtained by artificial modeling.
In a fifth aspect, there is also provided a product for preventing, alleviating and/or treating constipation, the product comprising lactobacillus gasseri B1-26 of the first aspect or the microbial agent of the second aspect; or, prepared by the fermentation method of the third aspect; or, comprising a fermentation product produced by the fermentation process of the third aspect. Exemplary products for preventing, alleviating and/or treating constipation include, but are not limited to, food products, nutraceuticals, and pharmaceuticals.
In an alternative embodiment, in the fourth and fifth aspects described above, the lactobacillus gasseri B1-26 or the bacterial agent comprising the same is the main functional ingredient of a product for preventing, alleviating and/or treating constipation, for example a health product or a pharmaceutical product.
In an alternative embodiment, in the fourth and fifth aspects described above, lactobacillus gasseri B1-26 or a bacterial agent comprising the same is used as a starter culture for the preparation of a product for preventing, alleviating and/or treating constipation, for example as a starter culture or additive for fermented food.
In an alternative embodiment, the fermentation process of the third aspect of the foregoing fourth and fifth aspects is used to prepare a product or a portion of a feedstock thereof for preventing, alleviating and/or treating constipation, for example for preparing a fermented food product, or for preparing a portion of a food, nutraceutical or pharmaceutical product to be fermented.
In an alternative embodiment, in the fourth and fifth aspects of the foregoing, the product for preventing, alleviating and/or treating constipation is a food product comprising lactobacillus gasseri B1-26 or a microbial agent comprising the same; or the food is prepared by fermenting a starter containing the lactobacillus gasseri B1-26; or, the food is obtained by fermenting a starter containing lactobacillus gasseri B1-26; or the food is prepared by adopting the fermentation method; or comprises the fermentation product prepared by the fermentation method. The food is optionally a non-fermented food or a fermented food, to which the present invention is not limited; such food products include, but are not limited to, fermented milk, cheese, probiotic-containing drinks or flavored milk, or food products with these food products as part or all of the raw material, or food products with these food products being further processed. It will be appreciated that the food product may also contain optional ingredients acceptable in the art, including but not limited to other edible portions, flavors, food additives, and the like, as the invention is not limited in this regard.
In an alternative embodiment, in the fourth and fifth aspects, the food product comprises a dairy product. Sources of milk in dairy products include, but are not limited to, humans, cows, sheep, horses, camels, and the like.
In an alternative embodiment, the food, nutraceutical and pharmaceutical products in the fourth and fifth aspects described above include food, nutraceutical and pharmaceutical products suitable for infants. Since lactobacillus gasseri B1-26 is derived from breast milk, lactobacillus gasseri B1-26 is preferably used for the preparation of infant products.
In an alternative embodiment, in the foregoing fourth and fifth aspects, the health product or the pharmaceutical product may further comprise optional ingredients acceptable in the art, including but not limited to optional excipients in the health product or pharmaceutical product field, for example, one or more of solvents, disintegrants, fillers, stabilizers, suspending agents, pH adjusters, thickeners, diluents, hollow capsules, matrices, and pharmaceutical carriers; and optionally one or more of auxiliary therapeutic ingredients, minerals, trace elements and amino acids.
The invention is further illustrated by the following specific examples, however, it should be understood that these examples are for the purpose of illustration only in greater detail and are not to be construed as limiting the invention in any way.
The experimental instrument and reagent information is as follows:
surgical scissors, ophthalmic forceps, ruler, syringe, balance, activated carbon powder, gum arabic 20200103;
MRS solid medium was purchased from Beijing land bridge technologies Co., ltd., product number CM188;
MRS broth medium was purchased from Beijing land bridge technologies Co., ltd., product number CM187;
loperamide hydrochloride: siam poplar pharmaceutical Co., ltd., product No. LFJ8473.
Experimental animals: vetolihua Kunming male mice were selected and used, with a body weight of 18-22g, and 120 SPF-grade male Kunming mice.
Positive control lactobacillus paracasei: the deposit number is GDMCC No.60960, see CN114032193A (China patent application with the name of "Lactobacillus paracasei 207-27 and application thereof", application number of CN202111331927. X).
Positive control bifidobacterium breve: the deposit number is GDMCC No.60962, see CN111944727A (China patent application with the name of "A.breve 207-1 and application thereof", application number CN 202010858666.6).
Example 1
Isolation and identification of milk-derived Lactobacillus gasseri B1-26:
fresh breast milk samples were selected, serially diluted with sterile PBS buffer (available from Jiete Biofiltration Co., ltd.) and applied to a sample containing 1% CaCO 3 Culturing for 48 hours in an anaerobic incubator at 37 ℃, picking up white or milky single colony with obvious transparent circle, carrying out gram staining and microscopic examination, selecting a strain which is rod-shaped and is gram positive, selecting a strain with better growth vigor from a plurality of strains, and carrying out enrichment culture in the anaerobic incubator at 37 ℃; screening to obtain a strain of lactobacillus gasseri; the bacterial liquid and the sterilized 30% glycerol are mixed according to the proportion of 1:1 and then stored in a refrigerator at the temperature of minus 80 ℃ for standby.
The selected strains were subjected to whole-genome sequencing analysis using Pacbio (10 Kb SMRT Bell library) and Illumina PE150 (350 bp small fragment library) sequencing platforms.
NR (Non-Redundant Protein Database) database annotation (for species information identification, for species classification) was performed on the sequencing results, and the results are shown in FIG. 1.
As can be seen from the results of FIG. 1, 93.61% of the gene Fu Gege of Lactobacillus was identified as Lactobacillus gasseri by combining the morphological characteristics of the selected strain, and designated as B1-26.
The colony morphology of lactobacillus gasseri B1-26 is: in the presence of 1% CaCO 3 After 48 hours of culture in MRS solid culture medium, the strain has obvious transparent rings, round shape, smooth surface and neat edge, and is white or milky white and is gram positive; the 16sRNA is shown as SEQ ID NO. 1; the colony morphology is shown in FIG. 2, and the microscopic morphology is shown in FIG. 3.
Example 2
The mice constipation experiments, the experimental groups are shown in table 1:
TABLE 1 grouping of experiments
(1) Small intestine movement experiment:
after 7 days of adaptive rearing, each group of mice fasted without water for 16 hours.
Loperamide hydrochloride (2-4 mg/kg BW) was given intragastrically to the model control group and to the three dose group, and distilled water was given to the blank control group.
After 0.5 hours from loperamide hydrochloride, the dose groups were given ink (5% active carbon powder, 10% gum arabic) with the corresponding test samples, respectively, and the negative and model control groups were given ink lavage.
Immediately after 25 minutes, the animals were sacrificed by cervical vertebra removal, the celiac separation mesentery was opened, the upper end from the pylorus, the lower end to the ileocecum were cut off, the intestinal canal was placed on a tray, the small intestine was gently pulled into a straight line, the length of the intestinal canal was measured as the "total length of the small intestine", and the front edge from the pylorus to the ink was the "push length of the ink". The ink push rate was calculated as follows:
(2) Measurement of defecation time, fecal particle count and fecal weight:
after 7 days of adaptive rearing, each group of mice fasted without water for 16 hours.
Loperamide hydrochloride (4-7 mg/kg BW) was given intragastrically to the model control group and to the three dose group, and distilled water was given to the blank control group.
After 0.5 hour after loperamide hydrochloride administration, the negative and model control groups were filled with ink, the dose groups were each fed with ink (5% active carbon powder, 10% gum arabic) containing the corresponding test samples, and animals were fed in single cages with normal drinking water.
The black discharge time, number of black discharge particles in 5 or 6 hours and weight of each animal were recorded from the start of ink filling.
As shown in the graph, from the thrust rate (fig. 4), stool weight (fig. 5) and stool particle (fig. 6), the high dose group and the model group were statistically different; demonstrating that lactobacillus gasseri B1-26 is effective for treating constipation; the ratio of the high dose group to the positive control group was not statistically different, indicating that lactobacillus gasseri B1-26 and the positive control were comparable in efficacy.
Finally, it should be noted that: the above embodiments are only for illustrating the technical solution of the present invention, and not for limiting the same; although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some or all of the technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit of the invention.
Claims (10)
1. Lactobacillus gasseri strainLactobacillus gasseri) B1-26, deposit number: CGMCC No.19749.
2. A microbial inoculum comprising the Lactobacillus gasseri strain according to claim 1Lactobacillus gasseri)B1-26。
3. A fermentation method comprising using a fermentation medium comprising Lactobacillus gasseri according to claim 1Lactobacillus gasseri) B1-26 fermenting the substrate with a starter; or fermenting a substrate with a starter comprising the microbial agent of claim 2.
4. Use of lactobacillus gasseri (Lactobacillus gasseri) B1-26 according to claim 1, or a microbial agent according to claim 2, or a fermentation process according to claim 3 for the preparation of a product for the prevention, alleviation and/or treatment of constipation.
5. The use according to claim 4, wherein the products for preventing, alleviating and/or treating constipation comprise food, health products and pharmaceutical products.
6. The use according to claim 5, wherein the food product comprises a dairy product.
7. The use according to any one of claims 4 to 6, wherein the use for preventing, alleviating and/or treating constipation comprises use for promoting gastrointestinal motility.
8. The use according to any one of claims 4 to 6, wherein the use for preventing, alleviating and/or treating constipation comprises increasing the amount of bowel movement in a subject.
9. A product for preventing, alleviating and/or treating constipation, characterized in that the product comprises the Lactobacillus gasseri strain according to claim 1Lactobacillus gasseri) B1-26 or the microbial agent of claim 2; or, the method is prepared by the fermentation method of claim 3; or comprises a fermentation product produced by the fermentation method of claim 3.
10. The product for preventing, alleviating and/or treating constipation according to claim 9, characterized in that said product comprises food, health products and medicines.
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