阅读说明：本技术 枸杞在调节肠道微生物中的用途 (Application of medlar in regulating intestinal microorganisms ) 是由 魏来 于 2019-04-18 设计创作，主要内容包括：本发明提供了一种枸杞在调节肠道微生物中的用途,所述用途为选择性的增加肠道中细菌的数量,或选择性的抑制肠道中细菌的数量,或选择性的增加肠道中病毒、真菌和原生动物的数量。本发明还提供枸杞和包含枸杞的组合物在制备药物中的应用,所述药物为预防和/或治疗与肠道微生物紊乱相关疾病的药物。(The invention provides application of medlar in regulating intestinal microorganisms, wherein the application is selectively increasing the number of bacteria in the intestinal tract, or selectively inhibiting the number of bacteria in the intestinal tract, or selectively increasing the number of viruses, fungi and protozoa in the intestinal tract. The invention also provides the use of lycium barbarum and of a composition comprising lycium barbarum in the manufacture of a medicament for the prevention and/or treatment of a disease associated with a microbial disorder of the intestinal tract.)

1. Use of fructus Lycii in regulating intestinal microorganism is provided.

2. The use of lycium barbarum in modulating gut microbes according to claim 1, wherein said modulating gut microbes is a selective increase or inhibition of the number of bacteria, viruses, fungi and protozoa in the gut.

3. Use of lycium barbarum according to claim 2 for modulating gut microbiota, wherein the increased number of bacteria in the gut is selected from the group consisting of: lactobacillus (Lactobacillus), Treponema (Treponema), Bacteroides (Bacteroides), Candida (Candida), butyric acid bacteria (Butyrivibrio), Campylobacter (Campylobacter), Roseburia (Roseburia), sitophilus (Victivallales), butyrate-producing bacteria (butyrate-producing bacteria), Coprococcus (Coprococcus), Libanicoccus, TLC (Hymenobacter), Parabacter (Parabaribacter), Phyciperae or a combination of two or more thereof.

4. Use of lycium barbarum in modulating gut microbiota according to claim 2, wherein the number of inhibited intestinal bacteria is selected from the group consisting of: one or a combination of two or more of Bacteroides (Bacteroides), Allophyllum (Alisiples), Prevotella (Prevotella), Streptococcus (Streptococcus), Lachnospiraceae (Lachnospiraceae), Lactobacillus (Lactobacillus), Desulfurovibrio (Desulfovibrio), Shigella (Shigella), Eubacterium (Eubacterium), Helicobacter (Helicobacter), Campylobacter (Campylobacter), and Escherichia (Escherichia).

5. Use of lycium barbarum in the modulation of gut microbes according to claim 2, wherein the increased number of viruses in the gut comprises bacteriophages.

6. Use of lycium barbarum in the modulation of gut microbes according to claim 2, characterized in that the increased number of protozoa in the gut comprises prototheca (blastocysts).

7. Use of lycium barbarum in the modulation of gut microorganisms according to claim 2, wherein the fungus in the increased number of gut comprises Trichoderma (Trichoderma).

8. The application of the medlar in preparing the medicine is characterized in that the medicine is the medicine for preventing and/or treating the diseases related to the intestinal flora disorder.

9. Use of lycium barbarum according to claim 8 in the manufacture of a medicament, wherein the disease is selected from: chronic diarrhea, constipation, obesity, food allergy, pancreatitis, liver injury, intestinal inflammation, irritable bowel syndrome, peptic ulcer, renal calculus, diabetes, rheumatoid arthritis, Behcet's disease, cardiovascular disease, cerebrovascular disease, tumor, paralysis, eye disease, multiple sclerosis, ankylosing spondylitis, Parkinson's disease, anxiety, autism, depression, chronic fatigue.

10. Use of a composition comprising lycium barbarum for modulating gut microbiota.

11. Use of a composition comprising lycium barbarum according to claim 10 for modulating gut microbiota, wherein said use is the selective increase or inhibition of the number of bacteria, viruses, fungi and protozoa in the gut.

12. The use of a composition comprising lycium barbarum in modulating gut microbiota according to claim 10, wherein the composition comprises lycium barbarum in combination with one or more than two selected from qi tonics, blood tonics, yin tonics, cold phlegm-warming and resolving herbs, blood-cooling hemostatics, blood stasis removing hemostatics, edema reliving and heat-clearing and blood-cooling herbs; the qi-tonifying medicine is selected from: one or more of radix Ginseng, radix Panacis Quinquefolii, radix Codonopsis, radix Pseudostellariae, radix astragali, rhizoma Atractylodis Macrocephalae, rhizoma Dioscoreae, semen lablab album, radix Glycyrrhizae, fructus Jujubae, radix Et caulis Acanthopanacis Senticosi, gynostemma pentaphyllum, radix Rhodiolae, fructus Hippophae, maltose, and Mel; the blood-tonifying agent is selected from: one or more of radix rehmanniae Preparata, radix Paeoniae alba, colla Corii Asini, Polygoni Multiflori radix, arillus longan, and fructus Broussonetiae; the yin-tonifying medicine is selected from: radix Glehniae, radix Adenophorae, Bulbus Lilii, radix Ophiopogonis, radix asparagi, herba Dendrobii, rhizoma Polygonati Odorati, rhizoma Polygonati, radix Changii, Ecliptae herba, fructus Ligustri Lucidi, Mori fructus, semen Sesami Niger, carapax et Plastrum Testudinis, carapax Trionycis, Tremella, nidus Collocaliae, and fish gelatin; the cold-phlegm warming and resolving medicine is selected from: one or more of rhizoma Pinelliae, rhizoma arisaematis, semen Sinapis Albae, fructus Gleditsiae Abnormalis, Inulae flos, Bulbus Fritillariae Cirrhosae, fructus Trichosanthis, caulis Bambusae in Taenia, succus Bambusae, concretio silicea Bambusae seu Schizostachyi, radix Peucedani, radix Platycodi, and semen Scaphii Lychnophori; the blood-cooling hemostatics are selected from: one or more of herba Cephalanoploris, herba seu radix Cirsii Japonici, radix Sangusorbae, flos Sophorae Immaturus, folium Platycladi, lalang grass rhizome, radix Curcumae, and radix Boehmeriae; the stasis-removing hemostatics are selected from: one or more of Notoginseng radix, radix Rubiae, pollen Typhae, Ophicalcitum, lignum Dalbergiae Odoriferae, and crinis Carbonisatus; the diuresis-inducing and edema-alleviating drug is selected from: poria, Coicis semen, Polyporus, Alismatis rhizoma, exocarpium Benincase, stigma Maydis, bottle gourd, cortex Periplocae Radicis, semen Hoveniae, herba Euphorbiae Helioscopiae, Gryllotalpa, and herba Capsellae; the heat-clearing and blood-cooling medicine is selected from: radix rehmanniae, charred radix Et rhizoma Rhei, radix scrophulariae, cortex moutan, radix Paeoniae Rubra, radix Arnebiae, cornu Bubali, and herba Rabdosiae Lophanthoidis.

13. Use of a composition comprising lycium barbarum in the manufacture of a medicament for the prevention and/or treatment of a disease associated with a disturbed intestinal flora.

14. The use of any one of claims 1 to 13, wherein the lycium barbarum is lycium barbarum or an extract of lycium barbarum.

15. The use according to claim 14, wherein the extract of lycium barbarum is extracted by a method selected from the group consisting of: solvent extraction, percolation, decoction, reflux, continuous reflux, ultrasonic extraction, supercritical fluid extraction, steam distillation, sublimation, resin adsorption separation or gel chromatography.

Technical Field

The invention belongs to the field of medicine and health care, and particularly relates to application of medlar in regulating intestinal microorganisms.

Background

The intestinal tract is an important organ for digestion, absorption and detoxification of the human body and is also the largest immune system of the human body. The human intestine includes three large segments, small intestine, large intestine and rectum, and the large intestine mainly concentrates food residue to form feces and discharges them out of the body through the rectum via anus. A huge number of microorganisms exist in the intestinal tract, wherein about 1000-1150 bacteria and about 100 trillion bacteria exist, and the number of the bacteria is close to 10 times of the number of somatic cells of a human body. Therefore, the intestinal tract is the most important 'endogenous environmental factor' of the human body. The intestinal microorganisms and metabolites thereof can regulate the health of human bodies and play an important bridge role between diet and hosts. Under normal conditions, the intestinal microorganisms are in a dynamic equilibrium ecological environment, the normal flora not only plays an irreplaceable role in digestion, immunity and virus resistance, but also the change of the intestinal microorganisms has a very close relationship with the health or diseases of the body, particularly the occurrence of some chronic diseases. The disturbance of intestinal flora impairs the barrier function of the intestinal tract and aggravates the disease by affecting the absorption of nutrients by the body. Researches have proved that the pathogenesis of various diseases of human body such as long-term diarrhea, constipation, obesity, food allergy, pancreatitis, liver injury, intestinal inflammation, irritable bowel syndrome, digestive tract ulcer, diabetes, Crohn's disease, cardiovascular diseases, tumor and the like is closely related to intestinal microorganisms. Thus, gut microbes have been identified as potential therapeutic targets for a variety of diseases.

Currently, the methods for regulating intestinal microorganisms are mainly drug, dietary intervention, probiotic, prebiotic and flora transplantation. For example, patent CN201780017713.0 provides methods of modulating gut microbiota by one or more defensins and/or GLP-1/GLP-1 analogs, such as liraglutide and mammalian and poultry alpha and beta defensins, which can cause alterations in the microbiota and metabolome composition in the gut, as well as methods of preventing or treating gut inflammation by orally administering one or more defensins. Patent CN201810364707.9 provides a composition for regulating intestinal microbial structure and proliferating acarman muciniphila, the composition comprises composite protein powder, oligosaccharide prebiotics, functional prebiotics and composite fat-soluble vitamins, the oligosaccharide prebiotics comprise short-chain inulin, fructo-oligosaccharide and resistant dextrin, the composite protein powder comprises concentrated lactalbumin, soybean protein isolate and collagen polypeptide, the functional prebiotics comprise one or more of metformin hydrochloride, tea polyphenol, anthocyanin and procyanidine, and the composite fat-soluble vitamins comprise vitamin A, vitamin E, vitamin D and vitamin K; the invention achieves the directional proliferation of the acamannia protein in caecum and ileum by the special proportion of a plurality of prebiotics, and adjusts the ratio of bacteroidetes/firmicutes in intestinal tracts.

As the life and work of modern people are accelerated and the diet is irregular, the condition of intestinal microorganism disorder of some people can be regulated by diet under most conditions, and researches show that traditional Chinese medicines and certain food with homology of medicine and food can regulate the intestinal microorganisms of human bodies or animals.

The medlar has slightly cold smell and sweet and bitter taste, and can tonify the kidney, improve the eyesight and the ears, calm the nerves, resist cold and summer heat, prolong life, supplement essence, strengthen marrow and strengthen bones. Patent CN201810937175.3 discloses a Chinese medicinal composition for treating rheumatism immune diseases and a preparation method thereof, wherein the Chinese medicinal composition comprises flatstem milkvetch root, medlar, desertliving cistanche, eucommia bark, cochinchnese asparagus root, tuckahoe, zaocys dhumnade, deerhorn glue, mulberry and borneol; the traditional Chinese medicine composition can effectively regulate intestinal microflora, enhance the immunity of the organism and enhance the repair and disease resistance of the organism. Patent CN200910217474.0 provides a Chinese medicinal colon-targeted microecological regulator prepared by mixing fructus Lycii polysaccharide extract, Bacillus bifidus and carbomer together, and encapsulating in polyacrylic resin capsule; the lycium barbarum polysaccharide is a prebiotic, the bifidobacterium is a probiotic, the prebiotic promotes the colonization and growth of the probiotic and colon-targeted dosage form, avoids the damage of the probiotic to the stomach and small intestine, promotes the growth of the human dominant bacteria bifidobacterium in vivo, and achieves the effects of adjusting the imbalance of intestinal flora and restoring the micro-ecological balance of the human body. At present, the research on specific strains regulated by medicines in the prior art is less, and in order to make up for the defect, the inventor carries out related research on specific strains for regulating intestinal tracts of Chinese wolfberry.

Disclosure of Invention

The invention provides application of medlar in regulating intestinal microorganisms.

The invention also provides application of the medlar in preparing a medicament, wherein the medicament is a medicament for preventing and/or treating diseases related to intestinal flora disorder.

The invention also provides the application of the composition containing the medlar in regulating intestinal microorganisms and the application of the composition in preparing a medicament for treating diseases related to intestinal flora disorder.

In particular, in a first aspect, the present invention provides the use of lycium barbarum in modulating gut microbes to selectively increase or inhibit the number of bacteria, fungi, viruses and protozoa in the gut. Specifically, the intestinal microorganism regulation can be used for selectively increasing the number of bacteria in the intestinal tract, selectively inhibiting the number of bacteria in the intestinal tract, selectively increasing the number of fungi and viruses in the intestinal tract, and selectively increasing the number of protozoa in the intestinal tract.

The modulating gut microbiome may be a selective increase in the number of bacteria in the gut selected from the group consisting of: lactobacillus (Lactobacillus), Treponema (Treponema), Bacteroides (Bacteroides), Candida (Candida), butyric acid vibrio (Butyrivibrio), Campylobacter (Campylobacter), Roseburia (Roseburia), sitophilus (Victivallales), butyrate producing bacteria (butyl-producing bacteria), Coprococcus (Coprococcus), Libanicoccus, TLC (Hymenobacter), Parabacter (Parabaribacter), Phyciperae or a combination of two or more thereof.

Preferably, the bacteria are selected from: one or more of Treponema, Candida, butyric vibrio, Roseburia, Gluconobacter, butyrate producing bacteria, fecal bacteria, Libanicoccus, TLC bacteria, Parabacillus bacteria, Physciera.

More preferably, the bacteria are selected from the group consisting of: two or more of Lactobacillus amylovorus, Treponema succinicides, uncultured Bacillus sp, Candidatus Melanicobacterium MEL.1, uncultured Bacillus Contigcl _1493, uncultured Bacillus CF, uncultured Bacillus focus pJB92C9, uncultured Bacillus LAB20, uncultured Bacillus Ad 143_ A19, uncultured Bacillus IN-02, Lactobacillus johnsonii, Buutyvibrio hungarii, Buutyricubrio proteococcus, Campylobacter fectus, Roseburia intemaligna, unculus faecalicus Q _025, Lactobacillus plantarum strain 4455, Lactobacillus strain 3955, Lactobacillus strain, Lactobacillus strain.

The intestinal microbes can also be regulated by selectively inhibiting the number of bacteria in the intestinal tract, wherein the bacteria are selected from the group consisting of: one or a combination of two or more of Bacteroides (Bacteroides), Allophyllum (Alisiples), Prevotella (Prevotella), Streptococcus (Streptococcus), Lachnospiraceae (Lachnospiraceae), Lactobacillus (Lactobacillus), Desulfurovibrio (Desulfovibrio), Shigella (Shigella), Eubacterium (Eubacterium), Helicobacter (Helicobacter), Campylobacter (Campylobacter), and Escherichia (Escherichia).

Preferably, the bacteria are selected from: one or more of Bacteroides, Arthrobacter, Desulfurovibrio, Shigella, Escherichia, Streptococcus, Prevotella, Eubacterium, helicobacter, and Muospira.

More preferably, the bacteria are selected from the group consisting of: bacterial genus OVatus, Alistepes shahii, Prevotella orius, Streptococcus agalactiae, Prevotella denticola, Bacillus vulgatus, Lachnospiraceae bacterium GAM79, Lactobacillus mucosae, Desufovibrio vulgare, Prevotella bivia, Shigella dysseniae, Lactobacillius agilis, unicuturedium IN-06, Prevotella sp.

The modulating gut microorganism may also be a selective increase in the number of viruses in the gut, said viruses comprising bacteriophages.

Preferably, the virus comprises unidentified phase.

The gut modulating micro-organism may also be selected to increase the number of protozoa comprising blastocysts in the gut.

Preferably, the protozoa are selected from the group consisting of: (ii) one or a combination of two or more of the following types of compounds selected from the group consisting of Blastocystis hominis, Blastocystis sp.

The modulating gut microbiome may also be a selective increase in the number of fungi in the gut, the fungi comprising Trichoderma (Trichoderma).

Preferably, the fungus comprises Trichoderma atroviride.

In a second aspect, the present invention also provides a use of lycium barbarum in the manufacture of a medicament for the prevention and/or treatment of a disease associated with a disturbed intestinal flora, preferably a disease selected from: chronic diarrhea, constipation, obesity, food allergy, pancreatitis, liver injury, intestinal inflammation including crohn's disease, irritable bowel syndrome, peptic ulcer, renal calculus, diabetes including gestational diabetes, rheumatoid arthritis, behcet's disease, cardiovascular disease, cerebrovascular disease including stroke, tumor, paralysis, eye disease, multiple sclerosis, ankylosing spondylitis, parkinson's disease, anxiety, autism, depression, chronic fatigue.

In a third aspect, the invention also provides the use of a composition comprising lycium barbarum in the regulation of intestinal microorganisms, wherein the composition comprises lycium barbarum in combination with one or more than two of qi tonics, blood tonics, yin tonics, cold phlegm-warming and resolving herbs, blood cooling hemostatics, blood stasis removing hemostatics, edema reliving drugs and heat-clearing and blood-cooling drugs.

The qi-tonifying medicine is selected from: one or more of radix Ginseng, radix Panacis Quinquefolii, radix Codonopsis, radix Pseudostellariae, radix astragali, rhizoma Atractylodis Macrocephalae, rhizoma Dioscoreae, semen lablab album, radix Glycyrrhizae, fructus Jujubae, radix Et caulis Acanthopanacis Senticosi, gynostemma pentaphyllum, radix Rhodiolae, fructus Hippophae, maltose, and Mel; preferably, the qi tonics are selected from: one or more of radix astragali, rhizoma Dioscoreae, and radix Rhodiolae; more preferably, the qi tonics are selected from: one or two of radix astragali and Ginseng radix.

The blood-tonifying agent is selected from: one or more of radix rehmanniae Preparata, radix Paeoniae alba, colla Corii Asini, Polygoni Multiflori radix, arillus longan, and fructus Broussonetiae; preferably, the hematinic agent is selected from: one or two of radix rehmanniae Preparata and radix Paeoniae alba.

The yin-tonifying medicine is selected from: radix Glehniae, radix Adenophorae, Bulbus Lilii, radix Ophiopogonis, radix asparagi, herba Dendrobii, rhizoma Polygonati Odorati, rhizoma Polygonati, radix Changii, Ecliptae herba, fructus Ligustri Lucidi, Mori fructus, semen Sesami Niger, carapax et Plastrum Testudinis, carapax Trionycis, Tremella, nidus Collocaliae, and fish gelatin; preferably, the yin-tonifying agent is selected from: one or more of radix Glehniae, Bulbus Lilii, radix Ophiopogonis, herba Dendrobii, and rhizoma Polygonati; more preferably, the yin-tonifying agent is selected from: rhizoma Polygonati.

The cold-phlegm warming and resolving medicine is selected from: one or more of rhizoma Pinelliae, rhizoma arisaematis, semen Sinapis Albae, fructus Gleditsiae Abnormalis, Inulae flos, Bulbus Fritillariae Cirrhosae, fructus Trichosanthis, caulis Bambusae in Taenia, succus Bambusae, concretio silicea Bambusae seu Schizostachyi, radix Peucedani, radix Platycodi, and semen Scaphii Lychnophori; preferably, the cold-phlegm warming and resolving medicine is selected from: one or more of rhizoma Pinelliae, rhizoma arisaematis, and radix Platycodi.

The blood-cooling hemostatics are selected from: one or more of herba Cephalanoploris, herba seu radix Cirsii Japonici, radix Sangusorbae, flos Sophorae Immaturus, folium Platycladi, lalang grass rhizome, radix Curcumae, and radix Boehmeriae; preferably, the blood-cooling hemostatics are selected from: one or more of lalang grass rhizome, radix Curcumae, and radix Sangusorbae.

The stasis-removing hemostatics are selected from: one or more of Notoginseng radix, radix Rubiae, pollen Typhae, Ophicalcitum, lignum Dalbergiae Odoriferae, and crinis Carbonisatus; preferably, the stasis-resolving hemostatics are selected from: and (4) pseudo-ginseng.

The diuresis-inducing and edema-alleviating drug is selected from: poria, Coicis semen, Polyporus, Alismatis rhizoma, exocarpium Benincase, stigma Maydis, bottle gourd, cortex Periplocae Radicis, semen Hoveniae, herba Euphorbiae Helioscopiae, Gryllotalpa, and herba Capsellae; preferably, the diuretic detumescence drug is selected from: one or more of Poria, Coicis semen, and stigma Maydis.

The heat-clearing and blood-cooling medicine is selected from: one or more of radix rehmanniae, charred radix Et rhizoma Rhei, radix scrophulariae, cortex moutan, radix Paeoniae Rubra, radix Arnebiae, cornu Bubali, and herba Rabdosiae Lophanthoidis; preferably, the heat-clearing and blood-cooling agent is selected from: one or more of radix rehmanniae, charred radix Et rhizoma Rhei, and radix scrophulariae.

The composition of the invention comprises 1-99 parts of medlar and one or more than two of qi tonics, blood tonics, yin tonics, cold phlegm warming and resolving medicines, blood cooling and bleeding stopping medicines, blood stasis removing and bleeding stopping medicines, diuresis inducing and edema diminishing medicines or heat clearing and blood cooling medicines in a ratio of 1-99 parts to 99-1 parts.

Preferably, the part ratio of the medlar to one or more than two of the drugs selected from qi-tonifying drugs, blood-tonifying drugs, yin-tonifying drugs, cold-phlegm-warming and resolving drugs, blood-cooling and bleeding-stopping drugs, blood stasis-removing and bleeding-stopping drugs, diuresis-inducing and edema-alleviating drugs or heat-clearing and blood-cooling drugs is 1-50: 50-1.

In a preferred embodiment of the invention, the composition is a combination of medlar and ginseng, and the weight parts ratio of medlar to ginseng is 1:1, 1:3 and 5:1 respectively.

In a preferred embodiment of the invention, the composition is a combination of medlar, rhizoma polygonati and radix paeoniae alba, and the weight part ratio of medlar to tuckahoe and radix rehmanniae is 1:1:1, 1:2:5 and 5:3:3 respectively.

Preferably, the composition further comprises pharmaceutically acceptable auxiliary materials, wherein the auxiliary materials are selected from the following components: a carrier, diluent, binder, lubricant, or wetting agent.

Preferably, the composition is in a dosage form selected from: tablet, capsule, pill, injection, inhalant, buccal tablet, suppository, emulsion, microemulsion, submicron emulsion, nanoparticle, gel, powder, suspension emulsion, cream, jelly, spray, etc.

Preferably, the composition may be administered in a manner selected from the group consisting of: oral administration, intestinal administration, subcutaneous injection, intramuscular injection, intravenous injection, nasal administration, transdermal administration, subconjunctival administration, intraocular administration, orbital administration, retrobulbar administration, retinal administration, choroidal administration, intrathecal injection, and the like.

In a fourth aspect, the invention also provides the use of the composition comprising lycium barbarum in modulating gut microbiota, to selectively increase or inhibit the number of bacteria, viruses, fungi and protozoa in the gut. In particular, the use may be for selectively increasing the amount of bacteria in the gut, for selectively inhibiting the amount of bacteria in the gut, and for selectively increasing the amount of viruses, protozoa and fungi in the gut.

The use of a composition comprising lycium barbarum in modulating gut microbiota may be for selectively increasing the number of bacteria in the gut selected from the group consisting of: lactobacillus (Lactobacillus), Treponema (Treponema), Bacteroides (Bacteroides), Candida (Candida), butyric acid bacteria (Butyrivibrio), Campylobacter (Campylobacter), Roseburia (Roseburia), sitophilus (Victivallales), butyrate-producing bacteria (butyrate-producing bacteria), Coprococcus (Coprococcus), Libanicoccus, TLC (Hymenobacter), Parabacter (Parabaribacter), Phyciperae or a combination of two or more thereof.

Preferably, the bacteria are selected from: one or more of Treponema, Candida, butyric vibrio, Roseburia, Gluconobacter, butyrate producing bacteria, fecal bacteria, Libanicoccus, TLC bacteria, Parabacillus bacteria, Physciera.

More preferably, the bacteria are selected from the group consisting of: two or more of Lactobacillus amylovorus, Treponema succinicides, uncultured Bacillus sp, Candidatus Melanicobacterium MEL.1, uncultured Bacillus Contigcl _1493, uncultured Bacillus CF, uncultured Bacillus focus pJB92C9, uncultured Bacillus LAB20, uncultured Bacillus Ad 143_ A19, uncultured Bacillus IN-02, Lactobacillus johnsonii, Buutyvibrio hungarii, Buutyricubrio proteococcus, Campylobacter fectus, Roseburia intemaligna, unculus faecalicus Q _025, Lactobacillus plantarum strain 4455, Lactobacillus strain 3955, Lactobacillus strain, Lactobacillus strain.

The use of a composition comprising lycium barbarum in modulating gut microbiota, optionally inhibiting the amount of bacteria in the gut selected from the group consisting of: one or a combination of two or more of Bacteroides (Bacteroides), Allophyllum (Alisiples), Prevotella (Prevotella), Streptococcus (Streptococcus), Lachnospiraceae (Lachnospiraceae), Lactobacillus (Lactobacillus), Desulfurovibrio (Desulfovibrio), Shigella (Shigella), Eubacterium (Eubacterium), Helicobacter (Helicobacter), Campylobacter (Campylobacter), and Escherichia (Escherichia).

Preferably, the bacteria are selected from: one or more of Bacteroides, Arthrobacter, Desulfurovibrio, Shigella, Escherichia, Streptococcus, Prevotella, Eubacterium, helicobacter, and Muospira.

More preferably, the bacteria are selected from the group consisting of: bacterial genus OVatus, Alistepes shahii, Prevotella orius, Streptococcus agalactiae, Prevotella denticola, Bacillus vulgatus, Lachnospiraceae bacterium GAM79, Lactobacillus mucosae, Desufovibrio vulgare, Prevotella bivia, Shigella dysseniae, Lactobacillius agilis, unicuturedium IN-06, Prevotella sp.

The use of a composition comprising lycium barbarum in modulating gut microbiota may also be used to selectively increase the number of viruses in the gut, said viruses comprising bacteriophage.

Preferably, the virus comprises unidentified phase.

The use of a composition comprising lycium barbarum in modulating gut microbiota may also be used to selectively increase the number of protozoa comprising blastocysts in the gut.

Preferably, the protozoa are selected from the group consisting of: (ii) one or a combination of two or more of the following types of compounds selected from the group consisting of Blastocystis hominis, Blastocystis sp.

The use of a composition comprising lycium barbarum in modulating gut microbiota may also be for selectively increasing the number of fungi in the gut, said fungi comprising Trichoderma (Trichoderma).

Preferably, the fungus comprises Trichoderma atroviride.

In a fifth aspect, the present invention provides the use of a composition comprising lycium barbarum in the manufacture of a medicament for the prevention and/or treatment of a disease associated with a microbial disorder of the intestinal tract, preferably a disease selected from: chronic diarrhea, constipation, obesity, food allergy, pancreatitis, liver injury, intestinal inflammation including crohn's disease, irritable bowel syndrome, peptic ulcer, renal calculus, diabetes including gestational diabetes, rheumatoid arthritis, behcet's disease, cardiovascular disease, cerebrovascular disease including stroke, tumor, paralysis, eye disease, multiple sclerosis, ankylosing spondylitis, parkinson's disease, anxiety, autism, depression, chronic fatigue.

In a sixth aspect, the present invention provides a method of modulating gut microbiota by ingesting wolfberry or a medicament comprising wolfberry in a manner selected from the group consisting of: oral administration, intestinal administration, subcutaneous injection, intramuscular injection, intravenous injection, nasal administration, transdermal administration, subconjunctival administration, intraocular administration, orbital administration, retrobulbar administration, retinal administration, choroidal administration, intrathecal injection, and the like.

The medlar comprises medlar, medlar leaves, medlar powder or medlar extract, and preferably the medlar is medlar or medlar extract.

The extraction method of the medlar extract is selected from the following steps: solvent extraction, percolation, decoction, reflux, continuous reflux, ultrasonic extraction, supercritical fluid extraction, steam distillation, sublimation, resin adsorption separation or gel chromatography.

Preferably, the extraction method is selected from: solvent extraction, decoction or resin adsorption separation.

In a seventh aspect, a method for preparing an extract of lycium barbarum comprises the steps of: (1) crushing, (2) extracting, (3) adsorbing and eluting, and (4) concentrating and drying.

Preferably, the preparation method of the medlar extract comprises the following steps:

(1) removing fruit stalks of fructus Lycii, air drying, and pulverizing to 80-300 mesh to obtain fructus Lycii powder;

(2) extracting fructus Lycii powder with solvent, filtering, and concentrating the filtrate under reduced pressure to obtain concentrated solution;

(3) adsorbing the concentrated solution by an adsorption column, eluting by purified water to remove impurities, and eluting by ethanol to obtain an eluent;

(4) and concentrating the eluent under reduced pressure, refining, concentrating under reduced pressure and drying to obtain the medlar extract.

Preferably, the medlar is crushed to 80 to 120 meshes in the step (1).

Preferably, the solvent in step (2) is selected from: n, N-dimethylformamide, acetic acid, dichloromethane, methanol, ethanol, isopropanol, tert-butanol, acetonitrile or acetone; preferably, the solvent is selected from: 40% -100% ethanol solution; more preferably, the solvent is selected from: 50% -80% ethanol solution.

Preferably, in the extraction in the step (2), the volume ratio of the medlar powder to the solvent is 1: 1-100, more preferably, the volume ratio is 1: 1-50.

Preferably, the packing of the adsorption column in step (3) is selected from: one or more than two of HPD series, ADS series, HZ series, XAD series and D series macroporous resin fillers; more preferably, the packing of the adsorption column is selected from: one or a combination of two or more of HPD100, HZ18, and D101.

Preferably, the drying manner in the step (4) is selected from: one or more of spray drying, vacuum drying, freeze drying, near infrared drying and microwave drying; more preferably, the drying mode is vacuum drying, and the drying temperature is 30-50 ℃.

Drawings

FIG. 1 altered gut microbial species of Lycium barbarum extract

Detailed Description