CN118203603A - Metagen and application thereof in regulating lipid metabolism direction - Google Patents
Metagen and application thereof in regulating lipid metabolism direction Download PDFInfo
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- CN118203603A CN118203603A CN202311768062.2A CN202311768062A CN118203603A CN 118203603 A CN118203603 A CN 118203603A CN 202311768062 A CN202311768062 A CN 202311768062A CN 118203603 A CN118203603 A CN 118203603A
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Landscapes
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
The application relates to a metagen and application thereof in regulating lipid metabolism direction. In particular, the application relates to the use of the metazoan in the preparation of a medicament or food. The application also relates to a method of modulating body weight in a subject, and a method of inhibiting or reducing lipid absorption in the gastrointestinal tract of a subject.
Description
Technical Field
The application relates to a metagen and application thereof in regulating lipid metabolism direction. In particular, the application relates to the use of the metazoan in the preparation of a medicament or food. The application also relates to a method of modulating body weight in a subject, and a method of inhibiting or reducing lipid absorption in the gastrointestinal tract of a subject.
Background
In modern society, the improvement of living standard, the gradual rise of fatness rate caused by high calorie diet and unhealthy life style such as sitting for a long time, and a series of metabolic abnormalities such as hyperlipidemia, nonalcoholic fatty liver and the like caused by excessive lipid deposition, and systemic inflammation and arteriosclerosis caused by fat cell dysfunction, thereby causing hypertension, cardiovascular diseases and the like. With the increase of the number of overweight and obese people, the incidence of the above diseases is rapidly rising, becoming a major health trouble for urban people in the current society, and the obese and overweight people are developing toward younger.
Current treatments for overweight or abnormal lipid metabolism rely mainly on lifestyle interventions, including low saturated fatty acid diets and medium and high intensity exercise activities. In addition, it is also possible to combine a pharmaceutical treatment, such as the lipase inhibitor drug orlistat; or taking medicine for treating hypertension or dyslipidemia and medicine for reducing cholesterol. These drugs have a certain effect on the treatment of obesity or abnormal lipid metabolism, but long-term administration causes serious side effects on liver and kidney functions.
The research shows that probiotics can play an important role in physiological metabolism of human body through the ways of generating metabolites, regulating intestinal flora and the like. According to the definition of probiotics given by the uk scientist Roy Fuller in 1989: a live microbial supplement, upon ingestion, exerts a beneficial host effect by improving intestinal microecological balance. The Chinese nutrition health care food society issues a group standard T/CNHFA 006-2022 Probiotics food viable ratio grading Specification to grade the Probiotics food viable ratio, emphasizes that the Probiotics have sufficient quantity to reach the intestinal tract, and is one of the basic conditions for the Probiotics to exert efficacy.
Recent scientific studies have shown that certain specific probiotic inactivation may also have their unique biological activity, known as "metazoan". "metazoan" is defined by the international society of probiotics and prebiotics science as: formulations of inanimate microorganisms and/or their related components that provide health benefits to a host. The efficacy of the metazoan comes from the microbial cells themselves and their growth metabolites. The metapreparation is generally considered to include: inactivated or dead microbial somatic cells; macromolecular substances such as proteins, lipids, carbohydrates, etc., secreted extracellularly or bound to the cell surface by microorganisms; microbial metabolites such as Short Chain Fatty Acids (SCFAs), organic acids, and the like; cell wall components such as lipoteichoic acid, peptidoglycan, etc. Along with the continuous deep scientific research, the definition and the category of metagen are also continuously perfected. Inactivated probiotics have natural advantages for commercial production and product applications compared to probiotics.
Therefore, an inactivated probiotic strain with the function of regulating or improving lipid metabolism abnormality is developed, and the strain has higher market value and wide application.
Disclosure of Invention
The applicant screens out a probiotic strain, namely bifidobacterium breve 207-1, at the early stage, and the microorganism preservation number is as follows: GDMCC No.60962. In the subsequent research process, the metazoan prepared by the strain after fermentation and inactivation has outstanding effects of promoting fat decomposition and/or inhibiting fat absorption. The metants and compositions comprising the same of the application therefore have great potential in the preparation of medicaments or foods for diseases and/or symptoms associated with increased fat.
Thus, in a first aspect, the present application provides the use of a metagen, or a composition comprising the metagen, in the manufacture of a medicament or foodstuff for preventing and/or ameliorating a disease and/or symptom associated with increased fat in a subject;
Wherein the metazoan is prepared by fermenting and inactivating bifidobacterium breve (Bifidobacterium breve) deposited in the cantonese microbiological strain collection center under the deposit number GDMCC No.60962.
Preparation of metazoan
The metants of the present invention may be prepared by various methods known in the art.
In certain embodiments, the metazoan is prepared by inactivating bifidobacterium breve (Bifidobacterium breve). In certain embodiments, the metazoan comprises bifidobacterium breve (Bifidobacterium breve) in the form of dead bacteria.
In certain embodiments, the metazoan is prepared by fermenting and inactivating bifidobacterium breve (Bifidobacterium breve). In certain embodiments, the metazoan comprises bifidobacterium breve (Bifidobacterium breve) in the form of dead bacteria, as well as primary and/or secondary metabolites produced during in vitro fermentation.
Herein, the metaverse may include a number of different components.
In certain embodiments, the metazoan comprises a bacterial composition of bifidobacterium breve. In certain embodiments, the metazoan comprises a cell lysate of bifidobacterium breve cells. In certain embodiments, the metazoan comprises peptidoglycan, lipoteichoic acid, cell wall peptide, cell wall polysaccharide, pilus structure, and the like.
In certain embodiments, the metazoan comprises a primary and/or secondary metabolite of bifidobacterium breve. In certain embodiments, the metazoan include short chain fatty acids (SCFA, such as acetic acid, propionic acid, and butyric acid), exopolysaccharides, functional proteins, vitamins (such as biotin, cobalamin, folic acid, niacin, pantothenic acid, pyridoxine, riboflavin, and thiamine), and the like.
In such embodiments, one of skill in the art may select an appropriate method to prepare the various dead bacterial forms of bifidobacterium breve contained in the metazoan. Thus, dosage forms of the metazoan include, but are not limited to, pills, powders, capsules, tablets (e.g., effervescent tablets), caplets, mouth-soluble granules, liquids.
In certain embodiments, the metazoan is a powder.
In certain embodiments, the metazoan is a bacterial powder.
In certain embodiments, the bacterial powder is prepared by the following method: culturing the bifidobacterium breve, and collecting and drying the sediment after inactivation.
In certain embodiments, the bacterial powder is prepared by the following method: and (3) inactivating the bifidobacterium breve after fermentation, centrifuging and collecting sediment, and carrying out vacuum freeze-drying.
In certain embodiments, the bifidobacterium breve is fermented by MRS medium.
In certain embodiments, the bifidobacterium breve is heat inactivated at 70 to 95 ℃.
In certain embodiments, the medicament or food is for preventing and/or ameliorating a disease and/or symptom caused by increased fat in a subject.
In certain embodiments, the disease and/or condition is selected from weight gain, obesity, fatty liver, fat accumulation (e.g., visceral fat accumulation, subcutaneous fat accumulation), abnormal lipid metabolism, or any combination thereof.
In certain embodiments, the subcutaneous fat deposit is selected from abdominal fat deposit, arm fat deposit, leg fat deposit, or any combination thereof.
In certain embodiments, the visceral fat accumulation is selected from the group consisting of periintestinal fat accumulation, perirenal fat accumulation, perigonadal fat accumulation, or any combination thereof.
In certain embodiments, the disorder resulting from abnormal lipid metabolism is selected from the group consisting of: hyperlipidemia, non-alcoholic fatty liver, hypertension, cardiovascular disease, or any combination thereof.
In certain embodiments, the obese subject has a BMI greater than 23.9kg/m2 (e.g., a BMI greater than 25kg/m 2, greater than 26kg/m 2, greater than 27kg/m 2, greater than 28kg/m 2, greater than 29kg/m 2, greater than 30kg/m 2).
In certain embodiments, the medicament or food product is capable of promoting lipolysis and/or inhibiting fat absorption.
In certain embodiments, the medicament or food product is capable of maintaining the weight and/or BMI of the subject.
In certain embodiments, the medicament or food product is capable of reducing the weight and/or BMI of the subject.
In certain embodiments, the medicament or food product is capable of providing the subject with a healthy BMI (e.g., 18.5-23.9kg/m 2).
In certain embodiments, the medicament or food is administered to a subject having a healthy BMI to maintain the weight and/or BMI of the subject. In certain embodiments, the medicament or food is administered to a subject who is overweight BMI to reduce the subject's body weight and/or BMI or to bring the subject's body weight and/or BMI towards healthy body weight and/or BMI (e.g., 18.5-23.9kg/m 2).
In certain embodiments, the medicament or food product is capable of increasing satiety in a subject upon administration to the subject.
In certain embodiments, the drug or food is capable of reducing the amount of food ingested by a subject after the drug or food is administered to the subject.
In certain embodiments, the medicament or food product further comprises an additional active ingredient (e.g., a compound).
In certain embodiments, the additional active ingredient is capable of promoting fat breakdown and/or inhibiting fat absorption; for example, L-carnitine (L-carnitine).
In certain embodiments, the additional active ingredient is capable of accelerating metabolism; for example tea polyphenols, caffeine.
In certain embodiments, the additional active ingredient is a lipase inhibitor; for example orlistat.
As used herein, the term "medicament" encompasses medicaments for humans as well as medicaments for animals (i.e., veterinary applications). In certain embodiments, the medicament is for use in humans.
In certain embodiments, the pharmaceutical composition comprises a formulation of a metagen.
In certain embodiments, the pharmaceutical composition comprises a pharmaceutically acceptable carrier.
In certain embodiments, the pharmaceutical composition is formulated for oral administration.
In certain embodiments, the drug or food is a drug that targets gastrointestinal release, or is a drug that is released in the gastrointestinal tract in a controlled manner.
In certain embodiments, the medicament is in the form of a pill, powder, capsule, tablet (e.g., effervescent tablet), caplet, mouth-soluble granule, liquid, suppository, or enema.
In the context of this document, the term "food" is used in a broad sense to include human foods and drinks, as well as animal foods and drinks (i.e., feeds). In certain embodiments, the food product is suitable and designed for human consumption.
It will be appreciated that the food product of the present application may be in the form of a liquid, solid, suspension or powder, depending on the application, mode of application or mode of administration.
In certain embodiments, the food product is selected from a solid beverage, a candy or a juice, or the food product is a dairy product (e.g., yogurt, flavored fermented milk, lactobacillus beverage, cheese).
In certain embodiments, the food product is a dietary supplement.
As used herein, the term "dietary supplement" refers to an edible product that is capable of providing a benefit (e.g., a nutritional effect, a prophylactic effect, a therapeutic effect, or other benefit) to a consumer. Dietary supplements in this context encompass health foods, biomedical foods, nutraceuticals, supplements, and the like.
In certain embodiments, the dietary supplement is formulated for oral administration.
In certain embodiments, the food product may further include (but is not limited to) one or any combination of the following: probiotics (e.g., probiotic bacteria), carbohydrates (e.g., dietary fibers), proteins (e.g., enzymes), lipids (e.g., fats), vitamins, minerals.
In certain embodiments, the food product may further comprise an immunomodulator.
In certain embodiments, the food product may also include a plant ingredient (e.g., flavonoids, polyphenol plant extracts, etc.), a milk substitute, or a metabolite or extract of bifidobacterium breve or progeny thereof.
In certain embodiments, the metates of the present invention may also be combined with various food acceptable adjuvants in sweeteners or flavors, color-modulating substances, stabilizers, glidants, fillers, and the like.
In certain embodiments, the food product further comprises a prebiotic.
In certain embodiments, the prebiotic is selected from the group consisting of fructooligosaccharides, galactooligosaccharides, xylooligosaccharides, isomaltooligosaccharides, soy oligosaccharides, inulin, spirulina, arthrospira, coriolus versicolor polysaccharides, nitrogen-containing polysaccharides from the group consisting of the plant, casein hydrolysates, alpha-lactalbumin, lactoferrin, or any combination thereof.
In certain embodiments, the food product is in the form of a pill, powder, capsule, tablet (e.g., effervescent tablet), caplet, mouth-soluble granule, liquid.
In certain embodiments, the subject is a mammal. In certain embodiments, the mammal is selected from the group consisting of a mouse, pig, rabbit, monkey, sheep, human.
In certain embodiments, the amount of metazoan added to the pharmaceutical or food product is from 0.001g to 0.1g.
In certain embodiments, the amount of metazoan added to the pharmaceutical or food product is from 0.001 to 0.005g, from 0.005 to 0.01g, from 0.01 to 0.05g, or from 0.05 to 0.1g.
It will be appreciated that it will be within the ability of one skilled in the art to administer an effective amount of metates to a subject, depending on the specific circumstances of the subject.
In some embodiments, the number of cells of the bifidobacterium breve is taken as the unit of measure of the bifidobacterium breve, since the metazoan contains inactivated bifidobacterium breve. In certain embodiments, the number of cells of bifidobacterium breve in the metazoan is 10 8-1014/g (e.g., 10 8-1010/g,1010-1012/g,1012-1014/g).
Therefore, when the added amount of the metazoan in the medicine or food is 0.001g, the number of cells of the metazoan is 10 5-1011. When the added amount of the metazoan in the medicine or food is 0.1g, the number of the bacterial cells of the metazoan is 10 7-1013.
In certain embodiments, the composition comprises the metazoan, and a microorganism selected from the group consisting of: bacteria, fungi, or any combination thereof.
In certain embodiments, the microorganism is a probiotic.
In certain embodiments, the microorganism is a yeast.
In certain embodiments, the yeast is selected from saccharomyces cerevisiae (Saccharomyces cerevisiae), saccharomyces boulardii (Saccharomyces boulardii), kluyveromyces marxianus (Kluyveromyces marxianus), or any combination thereof.
In certain embodiments, the bacteria are selected from the group consisting of Lactobacillus (Lactobacillus spp.), bifidobacterium (Bifidobacterium spp.), bacillus (Bacillus spp.), propionibacterium spp.), streptococcus (Streptococcus spp.), lactococcus (Lactococcus spp.), pediococcus (Pediococcus spp.), enterococcus (Enterococcus spp.), staphylococcus (Staphylococcus spp.), or any combination thereof.
In certain embodiments, the bacterium of the genus lactobacillus is selected from the group consisting of: lactobacillus paracasei, lactobacillus acidophilus (Lactobacillus acidophilus), lactobacillus brevis (Lactobacillus brevis), lactobacillus jensenii (Lactobacillus jensenii), lactobacillus inertia (Lactobacillus iners), lactobacillus casei (Lactobacillus casei), lactobacillus crispatus (Lactobacillus crispatus), lactobacillus curvatus (Lactobacillus curvatus), lactobacillus delbrueckii (Lactobacillus delbrueckii), lactobacillus fermentum (Lactobacillus fermentum), lactobacillus gasseri (Lactobacillus gasseri), lactobacillus helveticus (Lactobacillus helveticus), lactobacillus johnsonii (Lactobacillus johnsonii), lactobacillus plantarum (Lactobacillus plantarum), lactobacillus reuteri (Lactobacillus reuteri), lactobacillus rhamnosus (Lactobacillus rhamnosus), lactobacillus sake (Lactobacillus sakei), lactobacillus salivarius (Lactobacillus salivarius), or any combination thereof.
In certain embodiments, the bacterium of the genus bifidobacterium is selected from the group consisting of: bifidobacterium animalis (Bifidobacterium animalis), bifidobacterium bifidum (Bifidobacterium bifidum), bifidobacterium breve (Bifidobacterium breve), bifidobacterium infantis (Bifidobacterium infantis), bifidobacterium longum (Bifidobacterium longum), bifidobacterium adolescentis (Bifidobacterium adolescentis), or any combination thereof.
In certain embodiments, the bacteria of the genus bacillus are selected from the group consisting of: bacillus subtilis (Bacillus subtilis), bacillus coagulans (Bacillus coagulans), or any combination thereof.
In certain embodiments, the bacteria of the genus propionibacterium are selected from the group consisting of: propionibacterium scheelite (Propionibacterium shermanii), propionibacterium freudenreichii (Propionibacterium freudenreichii), propionibacterium propionicum (Propionibacterium acidipropionici), or any combination thereof.
In certain embodiments, the bacteria of the streptococcus genus are selected from: streptococcus thermophilus (Streptococcus thermophilus), streptococcus salivarius (Streptococcus salivarius), or any combination thereof.
In certain embodiments, the bacterium of the genus lactococcus is lactococcus lactis (Lactococcus lactis).
In certain embodiments, the bacterium of the enterococcus genus is selected from the group consisting of: enterococcus faecalis (Enterococcus faecalis), enterococcus faecium (Enterococcus faecium), enterococcus mundtii (Enterococcus mundtii), or any combination thereof.
In a second aspect, the application provides a method of regulating the weight of a subject, the method comprising: and administering to the subject an effective amount of a metagen, wherein the metagen is prepared by fermenting and inactivating bifidobacterium breve (Bifidobacterium breve) deposited with the cantonese province microorganism strain deposit center under accession number GDMCC No.60962.
In certain embodiments, the effective amount of metants is from 0.001g to 0.1g; for example, 0.001-0.005g,0.005-0.01g,0.01-0.05g,0.05-0.1g.
In certain embodiments, the obese subject has a BMI greater than 23.9kg/m2.
In certain embodiments, the method is capable of maintaining the weight of the subject.
In certain embodiments, the method is capable of reducing the weight of the subject.
In certain embodiments, the methods are capable of providing the subject with a healthy BMI (e.g., 18.5-23.9kg/m 2).
In certain embodiments, the subject is a mammal. In certain embodiments, the mammal is selected from the group consisting of a mouse, pig, rabbit, monkey, sheep, human.
In certain embodiments, the method is a method of modulating the body weight of a subject for non-therapeutic purposes.
In such embodiments, the subject is not suffering from or diagnosed with a disease (e.g., obesity).
In such embodiments, the subject has a healthy BMI.
In such embodiments, the subject is experiencing weight gain due to an unhealthy diet (e.g., a high fat diet, a high sugar diet, a high cholesterol diet) or environment.
In such embodiments, an effective amount of the metagen or a composition comprising the metagen is administered to a subject to maintain the weight and/or BMI of the subject or to reduce the weight and/or BMI of the subject.
In such embodiments, the frequency and manner in which the metazoan or composition comprising the metazoan is administered to a subject may be adjusted according to the characteristics of the subject (e.g., age, sex, race, weight, height, BMI, percentage of body fat, and/or medical history).
In another aspect, the application provides the use of a metagen or a composition comprising the metagen in the manufacture of a medicament or food for regulating the weight of a subject; wherein the metazoan is prepared by fermenting and inactivating bifidobacterium breve (Bifidobacterium breve) deposited in the cantonese microbiological strain collection center under the deposit number GDMCC No.60962.
In certain embodiments, the metazoan is added in an amount of 0.001g to 0.1g; for example, 0.001-0.005g,0.005-0.01g,0.01-0.05g,0.05-0.1g.
In certain embodiments, the subject is a mammal. In certain embodiments, the mammal is selected from the group consisting of a mouse, pig, rabbit, monkey, sheep, human.
In certain embodiments, the bifidobacterium breve (Bifidobacterium breve) is present in the metazoan in the form of a dead bacterium.
In such embodiments, one skilled in the art can select an appropriate method to prepare various dead bacterial dosage forms of bifidobacterium breve. Dead bacteria dosage forms include, but are not limited to, pills, powders, capsules, tablets (e.g., effervescent tablets), caplets, mouth-soluble granules, liquids.
In certain embodiments, the bifidobacterium breve is a powder.
In certain embodiments, the bifidobacterium breve is a bacterial powder.
In certain embodiments, the bacterial powder is prepared by the following method: culturing the bifidobacterium breve, and collecting and drying the sediment after inactivation.
In certain embodiments, the bacterial powder is prepared by the following method: and (3) inactivating the bifidobacterium breve after fermentation, centrifuging and collecting sediment, and carrying out vacuum freeze-drying.
In certain embodiments, the bifidobacterium breve is fermented by MRS medium.
In certain embodiments, the bifidobacterium breve is heat inactivated at 70 to 95 ℃.
In a third aspect, the application provides a method of inhibiting or reducing lipid absorption in the gastrointestinal tract of a subject, the method comprising: and administering to the subject an effective amount of a metagen, wherein the metagen is prepared by fermenting and inactivating bifidobacterium breve (Bifidobacterium breve) deposited with the cantonese province microorganism strain deposit center under accession number GDMCC No.60962.
In certain embodiments, the effective amount of metants is from 0.001g to 0.1g; for example, 0.001-0.005g,0.005-0.01g,0.01-0.05g,0.05-0.1g.
In certain embodiments, the method is capable of maintaining the weight of the subject.
In certain embodiments, the method is capable of reducing the weight of the subject.
In certain embodiments, the method is capable of maintaining a BMI (e.g., 18.5-23.9kg/m 2) in the subject.
In certain embodiments, the subject is a mammal. In certain embodiments, the mammal is selected from the group consisting of a mouse, pig, rabbit, monkey, sheep, human.
In certain embodiments, the methods are non-therapeutic methods for inhibiting or reducing lipid absorption in the gastrointestinal tract of a subject.
In such embodiments, the subject is not suffering from or diagnosed with a disease (e.g., obesity).
In such embodiments, the subject has a healthy BMI.
In such embodiments, the subject is experiencing weight gain due to an unhealthy diet (e.g., a high fat diet, a high sugar diet, a high cholesterol diet) or environment.
In such embodiments, an effective amount of a composition comprising the metagen is administered to a subject to maintain the weight and/or BMI of the subject or to reduce the weight and/or BMI of the subject.
In such embodiments, the frequency and manner in which the metazoan or composition comprising the metazoan is administered to a subject may be adjusted according to the characteristics of the subject (e.g., age, sex, race, weight, height, BMI, percentage of body fat, and/or medical history).
In another aspect, the application provides the use of a metagen or a composition comprising the metagen in the manufacture of a pharmaceutical composition for inhibiting or reducing lipid absorption in the gastrointestinal tract of a subject; wherein the metazoan is prepared by fermenting and inactivating bifidobacterium breve (Bifidobacterium breve) deposited in the cantonese microbiological strain collection center under the deposit number GDMCC No.60962.
In certain embodiments, the metazoan is added to the pharmaceutical or food product in an amount of 0.001g to 0.1g; for example, 0.001-0.005g,0.005-0.01g,0.01-0.05g,0.05-0.1g.
In certain embodiments, the subject is a mammal. In certain embodiments, the mammal is selected from the group consisting of a mouse, pig, rabbit, monkey, sheep, human.
In certain embodiments, the bifidobacterium breve (Bifidobacterium breve) is present in the metazoan in the form of a dead bacterium.
In such embodiments, one skilled in the art can select an appropriate method to prepare various dead bacterial dosage forms of bifidobacterium breve. Dead bacteria dosage forms include, but are not limited to, pills, powders, capsules, tablets (e.g., effervescent tablets), caplets, mouth-soluble granules, liquids.
In certain embodiments, the bifidobacterium breve is a powder.
In certain embodiments, the bifidobacterium breve is a bacterial powder.
In certain embodiments, the bacterial powder is prepared by the following method: culturing the bifidobacterium breve, and collecting and drying the sediment after inactivation.
In certain embodiments, the bacterial powder is prepared by the following method: and (3) inactivating the bifidobacterium breve after fermentation, centrifuging and collecting sediment, and carrying out vacuum freeze-drying.
In certain embodiments, the bifidobacterium breve is fermented by MRS medium.
In certain embodiments, the bifidobacterium breve is heat inactivated at 70 to 95 ℃.
Definition of terms
In the present invention, unless otherwise indicated, scientific and technical terms used herein have the meanings commonly understood by one of ordinary skill in the art. Meanwhile, in order to better understand the present invention, definitions and explanations of related terms are provided below.
As used herein, the term "lipid metabolism" is a biochemical reaction, and specifically refers to the process of synthesis, breakdown, digestion, absorption, and transport of lipid substances in an organism under the action of various related enzymes. The major lipid substances in blood include cholesterol, triacylglycerols (TAG), phospholipids (PL) and free fatty acids. In certain embodiments, the fat is processed into substances required by the body by fat metabolism, ensuring the functioning of normal physiology.
As used herein, the term "abnormal lipid metabolism" refers to the occurrence of abnormal synthesis, breakdown, digestion, absorption, and transport of lipid substances in the body, resulting in excessive or insufficient lipid in the tissue. Long-term high cholesterol, high saturated fatty acid and high caloric diets, genetic factors, abnormal apolipoproteins, mental labor, lack of exercise, mental stress, etc. may lead to abnormal lipid metabolism. Lipid metabolism abnormality may cause hyperlipidemia, non-alcoholic fatty liver, hypertension, and cardiovascular disease.
As used herein, the term "pharmaceutically acceptable carrier" refers to a carrier that is pharmacologically and/or physiologically compatible with the subject and active ingredient, as is well known in the art (see, e.g., Remington's Pharmaceutical Sciences.Edited by Gennaro AR,19th ed.Pennsylvania:Mack Publishing Company,1995), and including, but not limited to, pH modifiers, surfactants, adjuvants, ionic strength enhancers, e.g., pH modifiers include, but are not limited to, phosphate buffers, surfactants include, but are not limited to, cationic, anionic or nonionic surfactants, e.g., tween-80, ionic strength enhancers include, but are not limited to sodium chloride.
As used herein, the term "dietary supplement" refers to an edible product that is capable of providing a benefit (e.g., a nutritional effect, a prophylactic effect, a therapeutic effect, or other benefit) to a consumer. Dietary supplements in this context encompass products such as health products, nutrition, supplements, and the like.
As used herein, the term "drug" encompasses drugs in human and veterinary medicine for use by both humans and animals, as well as drugs for incorporation into animal feed (e.g., livestock feed and/or pet food). Furthermore, the term "drug" as used herein means any substance that provides a therapeutic, prophylactic and/or beneficial effect. The term "drug" as used herein is not necessarily limited to substances requiring a marketing license (MARKETING APPROVAL), but includes substances that may be used in cosmetics, health products, foods (including, for example, feeds and beverages), probiotic cultures, and dietary supplements.
Advantageous effects of the invention
The applicant screens out a probiotic strain, namely bifidobacterium breve 207-1, at the early stage, and the microorganism preservation number is as follows: GDMCC No.60962. During subsequent studies, it was unexpectedly found that the strain has a remarkable effect in promoting lipolysis and/or inhibiting fat absorption after inactivation. Thus, the strain of the present application and the composition comprising the same have great potential in preparing a medicament or food for diseases and/or symptoms associated with increased fat, for example, for diseases and/or symptoms of weight gain, obesity, fatty liver, fat accumulation, etc.
Embodiments of the present invention will be described in detail below with reference to the accompanying drawings and examples, but it will be understood by those skilled in the art that the following drawings and examples are only for illustrating the present invention and are not to be construed as limiting the scope of the present invention. Various objects and advantageous aspects of the present invention will become apparent to those skilled in the art from the following detailed description of the preferred embodiments and the accompanying drawings.
Drawings
FIG. 1 shows fluorescence intensity profiles of the treatment of zebra fish with different samples to promote lipolysis.
Figure 2 shows the intestinal and tail vessel fat staining of zebra fish after treatment of the zebra fish with different samples.
Fig. 3 shows graphs of the change in body weight of mice in different treatment groups at different time points, wherein #p <0.05 compared to the model group.
Figure 4 shows total weight gain before and after mice weight in different treatment groups, where #p <0.05 compared to model group.
Fig. 5 shows HE staining results of liver tissue of mice of different treatment groups.
Description of preservation of biological Material
Bifidobacterium breve 207-1 (Bifidobacterium breve 207,207-1) has been deposited with the Guangdong province microorganism strain collection (GDMCC, guangdong Microbial Culture Collection Center) located in building 5 of university No. 59, line 100, guangzhou, city martyr, with deposit No. GDMCC No.60962 and a deposit time of 2020, 1 month and 15 days.
Detailed Description
The invention will now be described with reference to the following examples, which are intended to illustrate the invention, but not to limit it.
The experiments and methods described in the examples were performed substantially in accordance with conventional methods well known in the art and described in various references unless specifically indicated. For example, for the conventional techniques of immunology, biochemistry, chemistry, molecular biology, microbiology, cell biology, genomics and recombinant DNA used in the present invention, reference may be made to Sambrook (Sambrook), friech (Fritsch) and manitis (Maniatis), molecular cloning: laboratory Manual (MOLECULAR CLONING: A LABORATORY MANUAL), edit 2 (1989); the handbook of contemporary molecular biology (CURRENT PROTOCOLS IN MOLECULAR BIOLOGY) (edited by f.m. ausubel et al, (1987)); the enzyme methods series (METHODS IN ENZYMOLOGY) (academic publishing Co): PCR2: practical methods (PCR 2: A PRACTICAL APPROACH) (M.J. MaxFrson (M.J. MacPherson), B.D. Hemsl (B.D. Hames) and G.R. Taylor (G.R. Taylor) editions (1995)), and animal cell CULTURE (ANIMAL CELL CULTURE) (R.I. French Lei Xieni (R.I. Freshney) editions (1987)).
In addition, the specific conditions are not specified in the examples, and the process is carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or apparatus used were conventional products commercially available without the manufacturer's attention. Those skilled in the art will appreciate that the examples describe the invention by way of example and are not intended to limit the scope of the invention as claimed. All publications and other references mentioned herein are incorporated by reference in their entirety.
Example 1 test Strain
Preparation method of metazoan
Fermenting the live bifidobacterium 207-1 with MRS culture medium at 35-37 deg.C for 24-72 hr, heat inactivating at 70-95 deg.C, centrifuging to obtain precipitate, vacuum freeze drying to obtain dried thallus, and sieving to obtain final metazoan. The metazoan is detected by each index including sensory requirements, net content, total number of lactic acid bacteria, number of thalli and coliform group, which meets the requirements of the national quality supervision and inspection and quarantine administration 75 # quantitative packaged commodity metering supervision and management method. The number of cells of Bifidobacterium breve 207-1 in the metazoan was 3X 10 11/g.
Experiment Strain origin
The bifidobacterium breve referred to in this experiment was derived from a Shang Chen-fold healthy pool of strains isolated from normal term neonatal faeces samples born at the birth Hospital of Sichuan university Hua Xifu. In particular to a convenient aseptic excrement collecting tube for collecting fresh excrement within 1-4 months after the birth of a baby. Immediately after sampling, the strain is temporarily stored at 4 ℃, the sample is sent to a laboratory at a low temperature for diluting and culturing the fecal sample, if the sample cannot be immediately operated, the sample is preserved at 4 ℃ anaerobically, the sample is cultured on the same day, then the sample is separated and purified by a plate method to obtain single strain, and the specific species of the separated strain are identified by adopting the API 50 CH and 16S rDNA sequencing of Mei Liai, numbered and then preserved in a Shang Chen times healthy own strain library. Among them, bifidobacterium breve 207-1 was deposited during the previous study because of its acid and bile salt resistance properties, and patented.
Example 2 evaluation of the efficacy of metazoan to promote fat decomposition in zebra fish
2.1 Laboratory animals
The black pigment allele mutant semitransparent Albino strain zebra fish is bred in water for breeding fish at 28 ℃ (water quality: 200mg instant sea salt is added into each 1L reverse osmosis water, conductivity is 450-550 mu S/cm, pH is 6.5-8.5, hardness is 50-100 mg/L CaCO 3), and the water is bred by the fish culture center of the company, and the use license number of experimental animals is: SYXK (Zhe) 2022-0004, the feeding management meets the requirements of international AAALAC authentication (authentication number: 001458).
Zebra fish were bred in natural pairwise manner, and zebra fish aged 2 days after fertilization (2 dpf) were used to determine the maximum detection concentration (MTC) of the sample for promoting lipolytic efficacy and their efficacy evaluation.
2.2MTC assay
2Dpf melanin allele mutant Albino strain zebra fish were randomly selected in 6-well plates, and 30 zebra fish were treated per well (experimental group). Samples were given separately in water while normal controls were set with a 3mL per well capacity. After 2 days of treatment at 28 ℃, the MTC of the sample on normal zebra fish was determined. Under the experimental conditions, the metaplasia promoting efficacy MTC is 2000 mug/mL.
2.3 Evaluation of lipolytic efficacy (phenotype)
2Dpf melanin allele mutant Albino strain zebra fish were randomly selected in 6-well plates, and 30 zebra fish were treated per well (experimental group). Samples were given in water-soluble form, respectively, with a positive control resveratrol of 11.4. Mu.g/mL (Shanghai Ala Biotechnology Co., ltd.) and a normal control group was set at a capacity of 3mL per well. After 1 day of treatment at 28 ℃, nile red dye was given in water to each experimental group. After the treatment is continued for 1 day at 28 ℃,10 zebra fishes are randomly selected from each experimental group, photographed under a fluorescence microscope, analyzed and data are collected by NIS-ELEMENTS D3.20.20 advanced image processing software, the fluorescence intensity of the zebra fish yolk sac fat is analyzed, and the effect of promoting fat decomposition of the sample is evaluated according to the statistical analysis result of the index. Statistical treatment results are expressed in mean+ -SE. Statistical analysis was performed using SPSS26.0 software, with p <0.05 indicating that the differences were statistically significant, and the experimental results are shown in table 1 and fig. 1.
Table 1. Results of sample lipolysis promoting efficacy evaluation experiment (n=10)
Note that: p <0.05, p <0.001 compared to normal control group
2.4 Evaluation of lipolytic efficacy (Gene)
Uncoupling protein 1 (ucp 1) (Gene ID: 83908) is a specific protein on the inner mitochondrial membrane. When activated, ucp1 uncouples oxidative phosphorylation of the mitochondrial respiratory chain, thereby inhibiting ATP synthesis in the body, releasing energy in the form of thermal energy, and increasing energy consumption in the body. There are studies showing that overexpression of ucp1 in white fat reduces body weight in obese mice, and activation of ucp1 increases energy output and decreases fatty acid synthesis.
And Universal RNA Extraction TL Kit C (Fingered bergamot vitamin technology Co., ltd.) is used for extracting the total RNA of each group of zebra fish in the step 1.3, and an ultraviolet-visible spectrophotometer is used for measuring the concentration and purity of the total RNA, so that the quality is qualified. 2.00. Mu.g total RNA from zebra fish samples was used to synthesize 20.0. Mu.L cDNA, and the ucp1 primer information is shown in Table 2, following the first strand cDNA synthesis kit.
TABLE 2 beta-actin and ucp1 Gene primer sequence information
The expression of the beta-actin and ucp1 genes was detected by q-PCR. The RNA relative expression of the ucp1 gene was calculated using beta-actin as an internal reference for gene expression. Statistical treatment results are expressed in mean+ -SE. Statistical analysis was performed using SPSS26.0 software, with p <0.05 indicating that the differences were statistically significant, and the results are shown in table 3.
TABLE 3 evaluation of sample lipolytic efficacy (ucp 1 Gene) experimental results (n=3)
Note that: p <0.01, p <0.001 compared to normal control group
The result shows that the metagen has the effect of promoting the lipolysis of the zebra fish, and is particularly characterized in that the fluorescence intensity of the yolk sac fat is obviously reduced compared with that of a control group, and the lipolysis effect is optimal at the action concentration of 2000 mug/mL.
At the gene level, the relative gene expression levels of ucp1 were significantly up-regulated after the inactivated metazoan treatment of 1000 μg/mL and 2000 μg/mL compared to the control group. This result suggests that the metazoan may reduce the body weight of obese mice by up-regulating the expression level of ucp 1.
Example 3 evaluation of the fat absorption Effect of metazoan on Zebra fish
3.1 Laboratory animals
Wild type AB strain zebra fish is bred in water for breeding fish at 28 ℃ (water quality: 200mg of instant sea salt is added into 1L of reverse osmosis water, conductivity is 450-550 mu S/cm, pH is 6.5-8.5, hardness is 50-100 mg/L CaCO 3), the water is bred by a fish breeding center of the company, and the use license number of experimental animals is: SYXK (Zhe) 2022-0004, the feeding management meets the requirements of international AAALAC authentication (authentication number: 001458).
Zebra fish are bred in a natural pairing mating breeding mode. Zebra fish of 5dpf in age were used for maximum detection concentration (MTC) determination of the efficacy of inhibiting fat absorption of the samples and efficacy evaluation thereof.
3.2MTC assay
The 5dpf wild type AB strain zebra fish were randomly selected in beakers, and 30 zebra fish were treated per beaker (experimental group). Samples were given in water-soluble form, and a normal control group and a model control group were simultaneously set, each cup having a capacity of 20mL. After treatment at 28 ℃ for 1 hour, all concentration groups except the normal control group are water-soluble, and pure yolk powder is fed to zebra fish to establish a food fat absorption model. After further treatment at 28℃for 1 day, the samples were assayed for MTC in model zebra fish. Under the experimental conditions, the metazoan inhibition fat absorption efficacy MTC is 2000 mug/mL.
3.3 Evaluation of fat absorption inhibition efficacy (phenotype)
The 5dpf wild type AB strain zebra fish were randomly selected in beakers, and 30 zebra fish were treated per beaker (experimental group). Samples were given in water-soluble form, respectively, with a concentration of 15.0. Mu.g/mL for the positive control orlistat (Shandong New time pharmaceutical Co., ltd.) and a capacity of 20mL per cup for the normal control group and the model control group. After treatment at 28 ℃ for 1 hour, all concentration groups except the normal control group are water-soluble, and pure yolk powder is fed to zebra fish to establish a food fat absorption model. After further treatment at 28 ℃ for 1 day, oil red O was given for bulk fat staining. After the decolorization and bleaching are finished, 10 zebra fish are randomly selected from each experimental group, photographed under an anatomic microscope, data are collected by using NIS-ELEMENTS D3.20.20 advanced image processing software, the fat staining intensity of intestinal tracts and tail blood vessels is analyzed, and the fat absorption inhibition effect of the sample is evaluated according to the statistical analysis result of the index. Statistical treatment results are expressed in mean+ -SE. Statistical analysis was performed with SPSS26.0 software, p <0.05 indicated that the differences were statistically significant. The results are shown in Table 4. The zebra fish intestinal tract and tail blood vessel fat staining is shown in figure 2.
Table 4. Evaluation of the efficacy of the samples in inhibiting fat absorption (phenotype) experimental results (n=10)
P <0.001 compared to model control group
3.4 Evaluation of fat absorption inhibition efficacy (Gene)
Adipor2 (Gene ID: 560140) encodes the adiponectin receptor AdipoR2. Adiponectin is a hormone secreted by adipocytes and increases fatty acid combustion and energy consumption. Adiponectin activates AMPK and pparα pathways, thereby stimulating fatty acid oxidation, increasing fatty acid combustion and lowering tissue cholesterol levels in the liver. AdipoR2 are full-length adiponectin receptors, mediating increased AMPK, pparα ligand activity, and adiponectin's ability to oxidize fatty acids and uptake glucose. Obesity reduces adiponectin levels and also reduces adipor levels of expression, resulting in reduced adiponectin sensitivity, reduced fatty acid burning capacity, and a vicious circle. The lepa Gene (Gene ID: 100150233) encodes the protein hormone leptin secreted by adipocytes. Leptin plays a major role in the regulation of energy homeostasis. Circulating leptin binds to leptin receptors in the brain, activating downstream signaling pathways that inhibit feeding and promote energy expenditure. Leptin levels may increase in obese conditions, thereby inhibiting food intake, while weight loss may result in decreased leptin levels, thereby increasing food intake.
The total RNA of each group of zebra fish in step 2.3 was extracted using Universal RNA Extraction TL Kit C and the total RNA concentration and purity were determined using an ultraviolet-visible spectrophotometer. 2.00. Mu.g of total RNA from the zebra fish sample was used to synthesize 20.0. Mu.L of cDNA according to the instructions of the cDNA first strand synthesis kit, and the primer information is shown in Table 5.
TABLE 5 primer sequence information for beta-actin, adimor 2 and lepa genes
The expression of the beta-actin, adimor 2 and lepa genes was detected by q-PCR, and the relative expression amounts of RNA of adipor and lepa genes were calculated using the beta-actin as an internal reference for gene expression. Statistical treatment results are expressed in mean+ -SE. Statistical analysis was performed with SPSS26.0 software, p <0.05 indicated that the differences were statistically significant. The results are shown in Table 6.
Table 6. Evaluation of fat absorption inhibition efficacy of samples (Gene) experimental results (n=3)
P <0.05, p <0.01, p <0.001 compared to model control group
The result shows that the metazoan has the effect of inhibiting the fat absorption of the zebra fish, and is particularly characterized in that compared with a model control group, the dyeing intensity of the fat of the intestinal tract and the tail blood vessel is obviously reduced, and compared with a positive medicament, the fluorescence intensity of the metazoan is lower than that of orlistat at different action concentrations, so that the metazoan has a better effect of inhibiting the fat absorption.
Compared with a model control group, the relative expression quantity of adipor genes can be obviously up-regulated after the metagen treatment at the gene level; down-regulating lepa gene relative expression quantity. This result suggests that the metazoan may inhibit fat absorption by regulating the relative expression amounts of these two genes.
Example 4 action study of metazoan to improve obesity in mice
8-Week-old male C57BL/6J mice are raised and kept at the ambient temperature of 21+/-2 ℃ and the humidity of 30-70%, and are alternately illuminated for 12 hours, and are free to drink water and take feed. After 7 days of adaptive feeding, the mice were randomly divided into 3 groups of 16 mice each. The control group (CON) was fed with normal feed and filled with normal saline; feeding high fat, high cholesterol and high fructose feed (HFHCD) and filling normal saline into the model group (HFD); feeding the inactivated bacteria group (HK 207-1) with high-fat high-cholesterol high-fructose feed and feeding the cells after stomach irrigation (feeding after 0.01g of inactivated bacteria powder is dissolved in 200ul of physiological saline); mice food intake and body weight were recorded weekly; mice were sacrificed at week 5 and blood was collected and viscera collected.
After the eyeball is sampled, standing the blood for more than 2 hours, centrifuging for 20 minutes at 2000 Xg and 4 ℃ to obtain a supernatant, centrifuging for 5 minutes again at 2000 Xg and 4 ℃ to separate serum. Liver, visceral fat (periintestinal + perirenal + perigonadal), inguinal subcutaneous fat were collected and weighed. H & E staining liver tissue; the amount of mRNA expressed in the lipogenic Gene SCD1 (Gene ID: 20249), lipolytic Gene HSL (Gene ID: 16890), involved in the fatty acid beta-oxidation Gene ACOX3 (Gene ID: 80911) was examined transcriptomically.
The weight of mice in the model group was significantly higher than that in the blank group (fig. 3) after 2 weeks of molding, and the total weight gain before and after the model group was far higher than that in the blank group, indicating that molding was successful. The weight of mice fed with metazoan was significantly lower than that of the model group after 5 weeks (fig. 4), and the total weight gain was significantly lower than that of the model group, and the results suggest that metazoan can improve obesity.
The accumulation of liver fat, subcutaneous fat and visceral fat of the mice fed with high fat is obviously higher than that of a blank group, and the intervention of metaplasia can obviously reduce the accumulation of liver fat and periintestinal and perirenal fat of the mice, so that the metaplasia has certain potential in improving subcutaneous fat accumulation, and the metaplasia can improve the problems of visceral fat accumulation, abdominal obesity and the like. Liver transcriptome data show that compared with a model group, the metagen intervention can significantly down-regulate a fat synthesis gene SCD1 and a gene ACOX3 participating in fat oxidation, and the result shows that the metagen intervention can have the effect of regulating fat metabolism by promoting fat decomposition and fat oxidation.
From the liver staining results (fig. 5), it can be seen that the model group fed with high fat causes balloon-like lesions to liver cells, and causes fatty liver to a certain extent, and intervention of metaplasia can alleviate the lesions, which indicates that metaplasia has the effect of improving fatty liver.
TABLE 7 visceral fat weight in mice
| Control group CON | Model set HFD | Probiotic 207-1 | |
| Liver fat/g | 0.916 | 1.127* | 1.013# |
| Subcutaneous fat/g | 0.330 | 0.636* | 0.530 |
| Periintestinal fat/g | 0.155 | 0.312* | 0.218# |
| Perirenal fat/g | 0.068 | 0.282* | 0.195# |
| Perigonadal fat/g | 0.386 | 0.732* | 0.669 |
P <0.05 compared to the blank group; compared to model group, #p <0.05
TABLE 8 expression level of genes involved in fat metabolism in liver
| Control group CON | Model set HFD | Probiotic 207-1 | |
| SCD1 | 1676.1 | 3999.6* | 2932.2# |
| HSL | 8.4 | 13.4* | 12.6 |
| ACOX3 | 11.2 | 13.9* | 16.3# |
P <0.05 compared to the blank group; compared to model group, #p <0.05
Although specific embodiments of the invention have been described in detail, those skilled in the art will appreciate that: many modifications and variations of details may be made to adapt to a particular situation and the invention is intended to be within the scope of the invention. The full scope of the invention is given by the appended claims together with any equivalents thereof.
Claims (10)
1. Use of a metagen or a composition comprising the metagen in the manufacture of a medicament or food for preventing and/or ameliorating a disease and/or symptom associated with increased fat in a subject;
Wherein the metazoan is prepared by fermenting and inactivating bifidobacterium breve (Bifidobacterium breve) deposited in the cantonese microbiological strain collection center under the deposit number GDMCC No.60962.
2. The use of claim 1, wherein the medicament or food is for preventing and/or ameliorating a disease and/or symptom caused by increased fat in a subject;
The disease and/or condition is selected from weight gain, obesity, fatty liver, fat accumulation (e.g., visceral fat accumulation, subcutaneous fat accumulation), abnormal lipid metabolism, or any combination thereof;
Preferably, the subcutaneous fat deposit is selected from abdominal fat deposit, arm fat deposit, leg fat deposit, or any combination thereof;
Preferably, the visceral fat accumulation is selected from the group consisting of periintestinal fat accumulation, perirenal fat accumulation, perigonadal fat accumulation, or any combination thereof;
Preferably, the obese subject has a BMI greater than 23.9kg/m 2 (e.g., a BMI greater than 25kg/m 2, greater than 26kg/m 2, greater than 27kg/m 2, greater than 28kg/m 2, greater than 29kg/m 2, greater than 30kg/m 2);
preferably, the medicament or food product is capable of promoting fat breakdown and/or inhibiting fat absorption;
preferably, the medicament or food is capable of maintaining the weight and/or BMI of the subject;
Preferably, the medicament or food is capable of reducing the weight and/or BMI of the subject;
Preferably, the medicament or foodstuff is capable of providing the subject with a healthy BMI (e.g., 18.5-23.9kg/m 2).
3. The use of claim 1 or 2, wherein the bifidobacterium breve (Bifidobacterium breve) is present in the medicament or food in the form of dead bacteria;
preferably, the medicament or food product is capable of increasing the feeling of satiety in a subject upon administration to the subject;
preferably, the medicament or food product is capable of reducing the amount of food ingested by the subject following administration to the subject;
preferably, the medicament or food product further comprises an additional active ingredient (e.g. a compound);
preferably, the additional active ingredient is capable of promoting fat breakdown and/or inhibiting fat absorption; for example, L-carnitine (L-carnitine);
Preferably, the additional active ingredient is capable of accelerating metabolism; for example, tea polyphenols, caffeine;
preferably, the additional active ingredient is a lipase inhibitor (e.g., orlistat).
4. The use of any one of claims 1-3, wherein the medicament has one or more characteristics selected from the group consisting of:
(1) The drug is targeted for gastrointestinal release or controlled release in the gastrointestinal tract;
(2) The medicament further comprises a pharmaceutically acceptable carrier;
(3) The medicament is in the form of a pill, powder, capsule, tablet (e.g., effervescent tablet), caplet, mouth-soluble granule, liquid, suppository or enema.
5. A use according to any one of claims 1 to 3, wherein the food product has one or more characteristics selected from the group consisting of:
(1) The food is a dietary supplement;
(2) The food product further comprises a prebiotic;
Preferably, the prebiotic is selected from fructooligosaccharides, galactooligosaccharides, xylooligosaccharides, isomaltooligosaccharides, soy oligosaccharides, inulin, spirulina, arthrospira, coriolus versicolor polysaccharides, nitrogen-containing polysaccharides from the group consisting of casein hydrolysates, alpha-lactalbumin, lactoferrin, or any combination thereof;
(3) The food product is selected from a solid beverage, a candy or a juice, or the food product is a dairy product (e.g. yoghurt, flavoured fermented milk, lactic acid bacteria beverage, cheese);
(4) The food is in the form of a pill, powder, capsule, tablet (e.g., effervescent tablet), film-covering agent, mouth-soluble granule, liquid.
6. The use according to any one of claims 1 to 5, having one or more features selected from the group consisting of:
(1) The subject is a mammal; preferably, the mammal is selected from the group consisting of mice, pigs, rabbits, monkeys, sheep, humans;
(2) The adding amount of the metazoan in the medicine or the food is 0.001g-0.1g;
(3) The added amount of metazoan in the medicine or food is 0.001-0.005g,0.005-0.01g,0.01-0.05g or 0.05-0.1g.
7. The use of any one of claims 1-6, wherein the composition comprises the metazoan, and a microorganism selected from the group consisting of: bacteria, fungi, or any combination thereof;
Preferably, the microorganism is a probiotic;
Preferably, the microorganism is yeast;
preferably, the yeast is selected from the group consisting of Saccharomyces cerevisiae (Saccharomyces cerevisiae), saccharomyces boulardii (Saccharomyces boulardii), kluyveromyces marxianus (Kluyveromyces marxianus), or any combination thereof;
Preferably, the bacteria are selected from the group consisting of Lactobacillus (Lactobacillus spp.), bifidobacterium (Bifidobacterium spp.), bacillus (Bacillus spp.), propionibacterium spp.), streptococcus (Streptococcus spp.), lactococcus spp.), pediococcus (Pediococcus spp.), enterococcus spp.), staphylococcus spp.
8. The use of claim 7, wherein the use has one or more features selected from the group consisting of:
(1) The bacterium of the genus lactobacillus is selected from the group consisting of: lactobacillus paracasei, lactobacillus acidophilus (Lactobacillus acidophilus), lactobacillus brevis (Lactobacillus brevis), lactobacillus jensenii (Lactobacillus jensenii), lactobacillus inertia (Lactobacillus iners), lactobacillus casei (Lactobacillus casei), lactobacillus crispatus (Lactobacillus crispatus), lactobacillus curvatus (Lactobacillus curvatus), lactobacillus delbrueckii (Lactobacillus delbrueckii), lactobacillus fermentum (Lactobacillus fermentum), lactobacillus gasseri (Lactobacillus gasseri), lactobacillus helveticus (Lactobacillus helveticus), lactobacillus johnsonii (Lactobacillus johnsonii), lactobacillus plantarum (Lactobacillus plantarum), lactobacillus reuteri (Lactobacillus reuteri), lactobacillus rhamnosus (Lactobacillus rhamnosus), lactobacillus sake (Lactobacillus sakei), lactobacillus salivarius (Lactobacillus salivarius), or any combination thereof;
(2) The bacterium of the genus bifidobacterium is selected from: bifidobacterium animalis (Bifidobacterium animalis), bifidobacterium bifidum (Bifidobacterium bifidum), bifidobacterium breve (Bifidobacterium breve), bifidobacterium infantis (Bifidobacteriuminfantis), bifidobacterium longum (Bifidobacterium longum), bifidobacterium adolescentis (Bifidobacterium adolescentis), or any combination thereof;
(3) The bacteria of the genus bacillus are selected from: bacillus subtilis (Bacillus subtilis), bacillus coagulans (Bacillus coagulans), or any combination thereof;
(4) The bacteria of the genus propionibacterium are selected from: propionibacterium scheelite (Propionibacterium shermanii), propionibacterium freudenreichii (Propionibacterium freudenreichii), propionibacterium propionicum (Propionibacterium acidipropionici), or any combination thereof;
(5) The bacteria of the streptococcus genus are selected from: streptococcus thermophilus (Streptococcus thermophilus), streptococcus salivarius (Streptococcus salivarius), or any combination thereof;
(6) The bacterium of the genus lactococcus is lactococcus lactis (Lactococcus lactis);
(7) The bacteria of the enterococcus genus are selected from: enterococcus faecalis (Enterococcus faecalis), enterococcus faecium (Enterococcus faecium), enterococcus mundtii (Enterococcus mundtii), or any combination thereof.
9. A method of regulating body weight in a subject, the method comprising: administering to the subject an effective amount of a metagen, wherein the metagen is prepared by fermenting and inactivating bifidobacterium breve (Bifidobacterium breve) deposited with the cantonese province microorganism strain deposit center under accession number GDMCC No.60962;
Preferably, the effective amount of metates is from 0.001g to 0.1g; for example, 0.001-0.005g,0.005-0.01g,0.01-0.05g,0.05-0.1g;
Preferably, the method is capable of maintaining the weight of the subject;
preferably, the method is capable of reducing the weight of the subject;
preferably, the method is capable of maintaining a BMI (e.g., 18.5-23.9kg/m 2) in the subject;
preferably, the subject is a mammal;
Preferably, the mammal is selected from the group consisting of mice, pigs, rabbits, monkeys, sheep, humans.
10. Use of a metagen, or a composition comprising the same, for the preparation of a pharmaceutical composition for inhibiting or reducing lipid absorption in the gastrointestinal tract of a subject wherein the metagen is prepared by fermentation and inactivation of bifidobacterium breve (Bifidobacterium breve) deposited at the cantonese province microorganism strain deposit under accession number GDMCC No.60962;
preferably, the pharmaceutical composition is capable of maintaining the weight of the subject;
preferably, the pharmaceutical composition is capable of reducing the weight of the subject;
Preferably, the pharmaceutical composition is capable of providing the subject with a healthy BMI (e.g., 18.5-23.9kg/m 2);
preferably, the subject is a mammal;
Preferably, the mammal is selected from the group consisting of mice, pigs, rabbits, monkeys, sheep, humans.
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