COMPOSITIONS AND APPLICATIONS WITH FUNCTIONS TO IMPROVE THE DIVERSITY OF PERSONALIZED INTESTINAL FLORA

Abstract

Provided is a composition functioning to improve personalized gut microbiota diversity function. The composition includes ingredients for strengthening spleen and invigorating Qi, ingredients for clearing damp and promoting the circulation of blood, and intestinal bacteria substrates. The ingredients for strengthening spleen and invigorating Qi include one or more of Panax ginseng, an extract of Panax ginseng, Panax quiquefolium, and an extract of Panax quiquefolium; the ingredients for clearing damp and promoting the circulation of blood include an ingredient for clearing damp and an ingredient for promoting the circulation of blood, where the ingredient for clearing damp includes one of or a mixture of more of Wolfiporia cocos and an extract of Wolfiporia cocos, and the ingredient for promoting the circulation of blood includes one of or a mixture of more of nattokinase, natto, and an extract of natto; the intestinal bacteria substrates include water-soluble dietary fiber, water-insoluble dietary fiber, or any combination thereof.

Claims

1. A composition functioning to improve personalized gut microbiota diversity, comprising ingredients for strengthening spleen and invigorating Qi, ingredients for clearing damp and promoting the circulation of blood, and intestinal bacteria substrates.

2. The composition functioning to improve personalized gut microbiota diversity according to claim 1, wherein the ingredients for strengthening spleen and invigorating Qi comprise one or more of Panax ginseng, an extract of Panax ginseng, Panax quiquefolium, and an extract of Panax quiquefolium.

3. The composition functioning to improve personalized gut microbiota diversity according to claim 1, wherein the ingredients for clearing damp and promoting the circulation of blood comprise an ingredient for clearing damp and an ingredient for promoting the circulation of blood, wherein the ingredient for clearing damp comprises one of or a mixture of more of Wolfiporia cocos and an extract of Wolfiporia cocos; and the ingredient for invigorating the circulation of blood comprises one of or a mixture of more of nattokinase, natto, and an extract of natto.

4. The composition functioning to improve personalized gut microbiota diversity according to claim 1, wherein the intestinal bacteria substrates comprise a water-soluble dietary fiber, a water-insoluble dietary fiber, or any combination thereof.

5. The composition functioning to improve personalized gut microbiota diversity according to claim 4, wherein the water-soluble dietary fiber comprises one or more of konjaku flour, glucomannan, crude laminarin, pectin, alginic acid, glucan, guar gum, inulin and Pericarpium citri reticulatae; or one or more of food ingredients or medicinal materials containing the above ingredients.

6. The composition functioning to improve personalized gut microbiota diversity according to claim 4, wherein the water-insoluble dietary fiber comprises one or more of cellulose, hemicellulose, and lignin.

7. The composition functioning to improve personalized gut microbiota diversity according to claim 1, further comprising one or more of Siraitia grosvenorii, an extract of Siraitia grosvenorii, almond, an extract of almond, perilla seed, and an extract of perilla seed.

8. The composition functioning to improve personalized gut microbiota diversity according to claim 1, wherein the ingredients for strengthening spleen and invigorating Qi comprise one or more of Panax ginseng, the extract of Panax ginseng, Panax quiquefolium, and the extract of Panax quiquefolium; the ingredients for clearing damp and promoting the circulation of blood comprise an ingredient for clearing damp and an ingredient for promoting the circulation of blood, wherein the ingredient for clearing damp comprises one of or a mixture of more of Wolfiporia cocos and an extract of Wolfiporia cocos; and the ingredient for promoting the circulation of blood comprises one of or a mixture of more of nattokinase, natto, and an extract of natto; a daily dose mainly consists of: TABLE-US-00023 One of or a mixture of more of Panax ginseng, the 0.001-2 g extract of Panax ginseng, Panax quiquefolium, and an extract of Panax quiquefolium One of or a mixture of more of Wolfiporia cocos and 0.001-5 g the extract of Wolfiporia cocos One of or a mixture of more of nattokinase, natto, and 500-4000 Fu the extract of natto Water-soluble dietary fiber by total weight of the 10%-70% composition Water-insoluble dietary fiber by total weight of the 10%-70% composition wherein an adding amount of the natto or the extract of natto is calculated by the fibrin degradation unit of the nattokinase contained therein.

9. The composition functioning to improve personalized gut microbiota diversity according to claim 8, wherein the daily dose mainly consists of: TABLE-US-00024 Ingredients for One of or a mixture of more of Panax 0.01-2 g strengthening ginseng and Panax quiquefolium spleen and Or, one of or a mixture of more of the 0.001-0.2 g invigorating extract of Panax ginseng and the Qi extract of Panax quiquefolium Ingredients for One of or a mixture of more of 0.001-5 g clearing damp Wolfiporia cocos and the extract of and promoting Wolfiporia cocos One of or a mixture of more of 500-4000 Fu the circulation nattokinase, natto, and the extract of of blood natto Water-soluble dietary fiber by total weight of the 10%-70% composition Water-insoluble dietary fiber by total weight of the 10%-70% composition wherein an adding amount of the natto or the extract of natto is calculated by the fibrin degradation unit of the nattokinase contained therein.

10. The composition functioning to improve personalized gut microbiota diversity according to claim 8, further comprising 0.1-3 g Siraitia grosvenorii or 0.001-0.5 g extract of Siraitia grosvenorii; or simultaneously or separately comprising 0.25-1 g) almond and/or 0.25-1 g perilla seeds.

11. The composition functioning to improve personalized gut microbiota diversity according to claim 1, wherein the water-soluble dietary fiber accounts for 20%-60% by the total dose of the formula; the water-insoluble dietary fiber accounts for 20%-60% by the total dose of the formula; calculated by the daily dose, the water-soluble dietary fiber or the water-insoluble dietary fiber has an adding amount of 1-10 g.

12. The composition functioning to improve personalized gut microbiota diversity according to claim 1, wherein calculated by the daily dose, the composition comprises the following ingredients: TABLE-US-00025 One of or a mixture of more of Panax ginseng 0.1-1 g or Panax quiquefolium or one of or a mixture of more of the extract of 0.01-0.04 g Panax ginseng or the extract of Panax quiquefolium Wolfiporia cocos 0.5-4 g Nattokinase 500-4000 Fu Guar gum 0.05-0.4 g Alginic acid 0.05-0.4 g Crude laminarin 0.05-0.4 g Pericarpium citri reticulatae 0.05-0.4 g Glucomannan 0.1-0.8 g Psyllium seed husk 0.25-2 g Siraitia grosvenorii 0.35-1.4 g.

13. A method of the preparation of a medicament, a health-care product or food functioning to improve personalized gut microbiota diversity, or in prevention, or treatment or adjunctive treatment of a gut microbiota imbalance-related disease utilizing the composition of claim 1.

14. The method according to claim 13, wherein the medicament is a medicament for prevention, or treatment or adjunctive treatment of an gut microbiota imbalance-related disease; the health-care product or food is a health-care product or food having a function of improving gut microbiota imbalance.

15. The method according to claim 14, wherein the gut microbiota imbalance comprises decreased gut microbiota diversity.

16. The method according to claim 14, wherein the gut microbiota imbalance comprises relatively strong strains and functions of dominant gut microbiota, and relatively less abundant strains and functions of gut microbiota.

17. The method according to claim 14, wherein the gut microbiota imbalance-related disease comprises metabolic diseases, immune system diseases, dermatological diseases, mental/neurogenic diseases and digestive diseases which are associated with gut microbiota imbalance, as well as a low sex hormone-related disease.

18. The method according to claim 17, wherein the metabolic dysfunction disease comprises prediabetes, type-II diabetes, obesity, cardiovascular diseases, cerebrovascular diseases, dyslipidemia, hypertension, hyperuricemia and renal dysfunction.

19. The method according to claim 17, wherein the immune system diseases comprises food/drug/pollen allergy, eczema, type-I diabetes, irritable bowel syndrome, inflammatory bowel disease, Crohn's disease, multiple sclerosis, rheumatoid, asthma and cancer.

20. The method according to claim 17, wherein the dermatological diseases comprises atopic dermatitis, psoriasis, eczema, acne, pachylosis and skin aging which are associated with gut microbiota imbalance.

21. The method according to claim 17, wherein the mental/neurogenic disease comprises depression, bipolar disorder, autism, schizophrenia, insomnia, Parkinson's disease, Alzheimer's disease and fibromyalgia.

22. The method according to claim 17, wherein the digestive system disease comprises constipation, diarrhea, fatty liver and liver cirrhosis.

23. The method according to claim 17, wherein the low sex hormone-related disease comprises developmental retardation of primary/secondary sex characters of children and adolescents, abnormality and disease associated with female physiological cycle and gestation period, osteoporosis caused by estrogen deficiency of postmenopausal female, male and female sexual hypofunction, and climacteric syndrome.

24. The method according to claim 13, wherein the medicament, health-care product or food is a medicament, health-care product or food having a function of enhancing body biodegradation to an exogenous toxic substance; the exogenous toxic substance comprises one or more of pesticides, herbicides, food additives, plastic residues, rubber residues, environmental pollutants, heavy metals, and other hazardous chemical substances.

25. The method according to claim 24, wherein the exogenous toxic substance comprises one or more of halobenzoic acid, halocyclohexane, halobenzene, caprolactam, 2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine, dioxin, aminobenzoate and xylene.

Description

BRIEF DESCRIPTION OF DRAWINGS

[0057] FIG. 1 is a Bristol Stool Chart;

[0058] FIG. 2a shows negative correlations of relative abundance between before and after administration of each bacterium (at the level of Phylum) (the left is a graphical result of 14-day dosing; the right is a graphical result of 30-day dosing);

[0059] FIG. 2b shows negative correlations of relative abundance between before and after administration of each bacterium (at the level of Class) (the left is a graphical result with 14-day dosing; the right is a graphical result with 30-day dosing);

[0060] FIG. 2c shows negative correlations of relative abundance between before and after administration of each bacterium (at the level of Order) (the left is a graphical result with 14-day dosing; the right is a graphical result with 30-day dosing);

[0061] FIG. 2d shows negative correlations of relative abundance between before and after administration of each bacterium (at the level of Family) (the left is a graphical result with 14-day dosing; the right is a graphical result with 30-day dosing);

[0062] FIG. 3 are graphical results showing an inhibitory effect of the solution provided by the examples on the relative abundance of the most dominant bacterium (at the level of Phylum), Bac_Firmicutes (the left is a graphical result with 14-day dosing; the right is a graphical result with 30-day dosing);

[0063] FIG. 4 are graphical results showing an inhibitory effect of the solution provided by the examples on the relative abundance of the second dominant bacterium (at the level of Phylum), Bac_Bacteroidetes (the left is a graphical result with 14-day dosing; the right is a graphical result with 30-day dosing);

[0064] FIG. 5 are graphical results showing an inhibitory effect of the solution provided by the examples on the relative abundance of the third dominant bacterium (at the level of Phylum), Bac_Proteobacteria (the left is a graphical result with 14-day dosing; the right is a graphical result with 30-day dosing);

[0065] FIG. 6 is a graphical result showing influences of the solution provided by the examples on the relative abundance of the less abundant bacterium (at the level of Phylum) with 14-day dosing;

[0066] FIG. 7 is a graphical result showing influences of the solution provided by the examples on the relative abundance of the less abundant bacterium (at the level of Phylum) with 30-day dosing;

[0067] FIG. 8 is a graphical result showing influences of the solution provided by the examples on a Bc_Firmicutes/Bc_Bacteroidetes ratio with 14-day dosing;

[0068] FIGS. 9a-9c are respectively graphical results showing influences of the solution provided by the examples on the relative abundance of Lachnospriraceae, Parabacteroides and Bacteroidetes with 14-/30-day dosing;

[0069] FIG. 10 is a graphical result showing related analysis on the change of the whole predicted metabolic pathways (213 types in total) with 14-/30-day dosing and the relative abundance before administration according to the solution provided by the examples;

[0070] FIG. 11 shows changes of the relative abundance of cell transformation-related genome with 14-/30-day dosing according to the solution provided by the examples;

[0071] FIG. 12 shows changes of the relative abundance of transcription-related genome with 14-/30-day dosing according to the solution provided by the examples;

[0072] FIG. 13a shows changes of the relative abundance of cytomembrane transport-related genome with 14-/30-day dosing according to the solution provided by the examples;

[0073] FIG. 13b shows changes of the relative abundance of electron transfer carriers-related genome with 14-/30-day dosing according to the solution provided by the examples;

[0074] FIG. 13c shows changes of the relative abundance of inorganic ion transport-related genome with 14-/30-day dosing according to the solution provided by the examples;

[0075] FIG. 13d shows changes of the relative abundance of pores ion channel-related genome with 14-/30-day dosing according to the solution provided by the examples;

[0076] FIG. 14 shows changes of the relative abundance of cell regeneration and repair-related genome with 14-/30-day dosing according to the solution provided by the examples;

[0077] FIG. 15 shows changes of the relative abundance of cell growth and death-related genome with 14-/30-day dosing according to the solution provided by the examples;

[0078] FIG. 16 shows changes of the relative abundance of apoptosis-related genome with 14-/30-day dosing according to the solution provided by the examples;

[0079] FIG. 17 shows changes of the relative abundance of ubiquitin system-related genome with 14-/30-day dosing according to the solution provided by the examples;

[0080] FIG. 18 shows changes of the relative abundance of glycan biosynthesis and metabolism with 14-/30-day dosing according to the solution provided by the examples;

[0081] FIG. 19 shows changes of the relative abundance of xenobiotics degradation-related genes with 14-/30-day dosing according to the solution provided by the examples;

[0082] FIGS. 20a and 20b respectively show changes of the relative abundance of a drug metabolism cytochrome p450 and a xenobiotics metabolism cytochrome p450 with 14-/30-day dosing according to the solution provided by the examples;

[0083] FIG. 21a shows changes of the relative abundance of terpenes and polyketones biosynthesis-related genes with 14-/30-day dosing according to the solution provided by the examples;

[0084] FIG. 21 shows changes of the relative abundance of type-II polyketones biosynthesis-related genes with 14-/30-day dosing according to the solution provided by the examples;

[0085] FIG. 22 shows changes of the relative abundance of cofactor and vitamin biosynthesis-related genes with 30-day dosing according to the solution provided by the examples;

[0086] FIG. 23a shows changes of the relative abundance of vitamins b1 and b2 synthesis-related genome with 30-day dosing according to the solution provided by the examples;

[0087] FIG. 23b shows changes of the relative abundance of vitamin b6 and folic acid synthesis-related genes with 30-day dosing according to the solution provided by the examples;

[0088] FIG. 23c shows changes of the relative abundance of vitamin b12 synthesis-related genes with 30-day dosing according to the solution provided by the examples;

[0089] FIG. 24 shows changes of the relative abundance of lipoic acid metabolism-related genes with 14-/30-day dosing according to the solution provided by the examples;

[0090] FIG. 25 shows changes of the relative abundance of carbohydrate metabolism-related genes with 14-/30-day dosing according to the solution provided by the examples;

[0091] FIG. 26a shows changes of the relative abundance of lipid metabolism-related genes with 14-/30-day dosing according to the solution provided by the examples;

[0092] FIG. 26b shows changes of the relative abundance of bile secretion-related genes with 14-/30-day dosing according to the solution provided by the examples;

[0093] FIG. 27 shows changes of the relative abundance of α-linolenic acid metabolism-related genes with 14-/30-day dosing according to the solution provided by the examples;

[0094] FIG. 28 shows changes of the relative abundance of amino acid metabolism-related genes with 14-/30-day dosing according to the solution provided by the examples;

[0095] FIG. 29 shows changes of the relative abundance of tryptophan-related genes with 14-/30-day dosing according to the solution provided by the examples;

[0096] FIG. 30 (the left) shows changes of the relative abundance of serotonin biosynthesis-related genes with 30-day dosing according to the solution provided by the examples;

[0097] FIG. 30 (the right) shows changes of the relative abundance of genes related to the biosynthesis of serotonin in the crowd with weak relative synthetic ability with 14-/30-day dosing according to the solution provided by the examples;

[0098] FIG. 31 shows changes of the relative abundance of lysine biosynthesis and metabolism-related genes with 30-day dosing according to the solution provided by the examples;

[0099] FIG. 32 shows changes of the relative abundance of acetic acid/propionic acid/butyric acid biosynthesis-related genes with 30-day dosing according to the solution provided by the examples;

[0100] FIG. 33a shows changes of the relative abundance of endocrine system-related genes with 14-/30-day dosing according to the solution provided by the examples;

[0101] FIG. 33b shows changes of the relative abundance of steroids hormone biosynthesis and metabolism-related genes with 14-/30-day dosing according to the solution provided by the examples;

[0102] FIG. 34a shows changes of the relative abundance of polysaccharide (LPS) biosynthesis-related genes with 14-/30-day dosing according to the solution provided by the examples;

[0103] FIG. 34b shows changes of the relative abundance of LPS biosynthetic protein-related genes with 14-/30-day dosing according to the solution provided by the examples;

[0104] FIG. 35 shows changes of the relative abundance of Pantoea gut microbiota with 14-/30-day dosing according to the solution provided by the examples;

[0105] FIG. 36 shows changes of the relative abundance of RIG-I-like receptor signal transduction-related genes with 14-/30-day dosing according to the solution provided by the examples;

[0106] FIG. 37 shows changes of the Bristol Stool Score with 14-/30-day dosing according to the solution provided by the examples;

[0107] FIG. 38 shows changes of Modified Cleveland Stool Score with 14-/30-day dosing according to the solution provided by the examples;

[0108] FIG. 39a shows changes of the serum total cholesterol before and after administration 30-day dosing according to the solution provided by the examples;

[0109] FIG. 39 shows changes of the serum low density lipoprotein cholesterol before and after administration 30-day dosing according to the solution provided by the examples;

[0110] FIG. 39 shows changes of the serum high density lipoprotein cholesterol before and after administration 30-day dosing according to the solution provided by the examples;

[0111] FIG. 40 shows changes of the serum triglyceride before and after administration 30-day dosing according to the solution provided by the examples;

[0112] FIG. 41 shows changes of fasting blood-glucose before and after administration 30-day dosing according to the solution provided by the examples;

[0113] FIG. 42 shows improvement effects on glucose tolerance test with 30-day dosing according to the solution provided by the examples;

[0114] FIG. 43 shows changes of serum uric acid before and after administration 30-day dosing according to the solution provided by the examples;

[0115] FIG. 44 shows changes of serum creatinine with 30-day dosing according to the solution provided by the examples;

[0116] FIG. 45 shows a correlation between the concentration of serum creatinine before and after 30-day dosing according to the solution provided by the examples;

[0117] FIG. 46 shows changes of serum creatinine in volunteers with low serum creatinine before and after 30-day dosing according to the solution provided by the examples;

[0118] FIG. 47 shows improvement on the estimated glomerular filtration rate before and after 30-day dosing according to the solution provided by the examples;

[0119] FIG. 48 shows improvement on the alanine aminotransferase and aspartate aminotransferase before and after 30-day dosing according to the solution provided by the examples.

DETAILED DESCRIPTION OF EMBODIMENTS

[0120] The compositions in Examples 1-7 are specified as follows: Panax ginseng is selected as a monarch drug of the compositions. Panax ginseng tastes sweet and a little bitter, and is warm and mild-natured. Panax ginseng is governed by the spleen, lung and heart meridians. Panax ginseng can reinforce vital energy, invigorate spleen for benefiting lung, promote the secretion of saliva and calm the nerves. Panax ginseng is selected as a representative drug for invigorating Qi and strengthening the spleen in the composition. Spleen governs movement and transformation, and is the foundation of acquired constitution; the nourishment of Qi and spleen makes body full of energy and blood, and full of vitality. Weak Qi and spleen lead to Weak movement and transformation, causing damp obstruction, Qi stagnation and blood stasis. Spleen prefers dryness to dampness, if the spleen is damp, movement and transformation are abnormal. Wolfiporia cocos tastes sweet and slight, is mild-natured. Wolfiporia cocos is governed by heart, lung, spleen and kidney channels, capable of clearing damp and promoting diuresis, strengthening spleen and calming heart. Wolfiporia cocos serves as the representative drug for strengthening spleen and clearing damp in the composition, and is a ministerial drug of the composition. Nattokinase is a kind of serine protease produced by Bacillus subtilis natto during soybean fermentation, found and named by a Japanese doctor, Hiroyuki Sumi. Nattokinase dissolves thrombus by direct and indirect ways. Nattokinase may stimulate vascular endothelial cells to produce a tissue-type plasminogen activator (t-PA). t-PA activates plasminogen into plasmin to dissolve fibrous proteins, thus dissolving thrombus directly. Meanwhile, prourokinase in human body is activated into urokinase; urokinase and t-PA co-activate plasminogen, thus indirectly dissolving thrombus. Therefore, the thrombolysis activity of nattokinase is about four times of plasmin. Nattokinase is selected as the representative drug for promoting the circulation of blood and removing stasis in the composition, and is another ministerial drug of the prescription. Compound types of gut microbiota substrates are combined in the composition. The substrates basically include different structures of water-soluble dietary fibers mainly derived from plants, including pectin, glucomannan, alginic acid and guar gum. Pectin is a kind of water-soluble dietary fiber which is abundant in fruits; galacturonic acid having carboxyl is connected with methyl galacturonicate whose carboxyl is esterified by methyl in a linear chain. Pericarpium citri reticulatae (total pectin is about 33%) rich in multiple types of pectin is selected in the composition (Akiko Kawabata, et al, Journal of Nutrition, 1974). Pericarpium citri reticulatae is warm-natured and governed by lung and spleen channels, and has the effects of regulating Qi and strengthening spleen, eliminating dampness to reduce phlegm. Glucomannan is a kind of water-soluble dietary fiber which is abundant in konjak plants. Glucomannan mainly consists of glucose and its diastereoisomers; β (1-4) bonds form a backbone chain, some form branched chains via β (1-3) or β (1-6) bonds. Alginic acid is a kind of water-soluble dietary fiber contained in brown seaweed, and is a linear polymer, divided into two types of β-D-mannuronic acid (M) and C-5 epimer α-L-guluronic acid (G) (both are carboxyl-carrying monosaccharides) (1-4). Crude laminarin is also called laminarin and laminaran, and mainly contains algin, fucoidan, fucose and other components, and formed by linking β(1-3)-glucan to some β(1-6)-glucosidic bonds, and is a neutral glucan. Guar gum is a kind of water-soluble dietary fiber derived from the seeds of annual leguminous plants cultivated in Pakistan and India; guar gum is a kind of polysaccharide composed of repetitive units; the backbone consists of mannose and the side chain consists of galactose. Psyllium seed husk contains about 90% dietary fiber, and is a mixture of insoluble and water-soluble dietary fibers. Psyllium seed husk contains about 18% heteropolysaccharide xylan, and is a kind of water-soluble dietary fiber. The above compound types of water-soluble dietary fibers may provide respective substrates demanded for different types of gut microbiota. The water-insoluble dietary fiber includes cellulose, hemicellulose, and lignin. Wolfiporia cocos is a kind of dry sclerotium of Poria cocos (Schw.) Wolf. Wolfiporia cocos not only has the effects of strengthening spleen and clearing damp and thus, serves as a ministerial drug of the composition, and but also contains more than 90% water-insoluble dietary fiber and thus, has adjuvant effects. Psyllium seed husk contains about 72% water-insoluble dietary fibers. The water-insoluble dietary fiber may provide a small amount of substrates for gut microbiota, what's more, may increase the water content of feces several times to hundreds of times, thus increasing the volume of excrement, beneficial to defecation. The above water-soluble and water-insoluble dietary fibers constitute the adjuvant drug of the composition. Siraitia grosvenorii is brought into spleen and large intestine channels, and serves as a conductant drug. The mogmside contained in the Siraitia grosvenorii is sweeter 300 times than sucrose, and featured by no energy, high sweetness, pure sweet taste and high safety, and is one of the most excellent natural and healthy sweetening agents. Moreover, Siraitia grosvenorii also plays the role of improving the taste of the composition.

Example 1: Composition 1

[0121]

TABLE-US-00005 Compatibility Dose Composition principle (g) Panax ginseng Monarch drug 0.25 Wolfiporia cocos Ministerial drug 1.00 Nattokinase (powder) 1000 Fu Water-soluble and Guar gum Adjuvant drug 0.20 water-insoluble Alginic acid 0.20 dietary fiber Crude laminarin 0.20 Pericarpium citri 0.20 reticulatae Glucomannan 0.40 Psyllium seed husk 1.00 Siraitia grosvenorii Conductant drug 0.70

[0122] The above components were crushed, sieved and mixed well to prepare a unit amount of the composition 1 in the present invention (namely, the amount of the following “per bag”). The composition may exert two-way regulation on the types and functions of gut microbiota, thus improving and maintaining personalized gut microbiota diversity. Moreover, the composition may keep healthy and have treatment or prevention effects on chronic diseases, in particular to metabolic diseases, immune diseases, mental/neurogenic diseases and other diseases incapable of being treated very well at present. A bag of the composition was brewed and taken once or twice per day with warm water.

Example 2: Composition 2

[0123]

TABLE-US-00006 Compatibility Dose Composition principle (g) Panax ginseng Monarch drug 0.13 Wolfiporia cocos Ministerial drug 0.50 Nattokinase (powder) 500 Fu Water-soluble and Guar gum Adjuvant drug 0.10 water-insoluble Alginic acid 0.10 dietary fiber Crude laminarin 0.10 Pericarpium citri 0.10 reticulatae Glucomannan 0.20 Psyllium seed husk 0.50 Siraitia grosvenorii Conductant drug 0.35

[0124] The formula of this example may be used as an introducing prescription, or applied to the inadaptable subjects, such as, patients accompanied with continuous abdominal distension, or stomachache after taking the composition 1. The composition may exert two-way regulation on the types and functions of gut microbiota, thus improving and maintaining personalized gut microbiota diversity. Moreover, the composition may keep healthy and have treatment or prevention effects on chronic diseases, in particular to metabolic diseases, immune diseases, mental/neurogenic diseases and other diseases incapable of being treated very well at present. A bag of the composition (namely, the components and contents as shown in the above corresponding table) was brewed and taken once or twice per day with warm water.

Example 3: Composition 3

[0125]

TABLE-US-00007 Compatibility Dose Composition principle (g) Panax ginseng Monarch drug 0.50 Wolfiporia cocos Ministerial drug 2.00 Nattokinase (powder) 2000 Fu Water-soluble and Guar gum Adjuvant drug 0.4 water-insoluble Alginic acid 0.4 dietary fiber Crude laminarin 0.4 Pericarpium citri 0.4 reticulatae Glucomannan 0.8 Psyllium seed husk 2.00 Siraitia grosvenorii Conductant drug 0.70

[0126] The formula in the example is suitable for the patient whose feces is not improved obviously or improved slowly towards the intermediate type (type 4) of the Bristol Stool Scale after taking the composition 1 in Example 1. The above components were crushed, sieved and mixed well to prepare a unit amount of the composition 3 in the present invention. The composition may exert two-way regulation on the types and functions of gut microbiota, thus improving and maintaining personalized gut microbiota diversity. Moreover, the composition may keep healthy and have treatment or prevention effects on chronic diseases in particular to metabolic diseases, immune diseases, mental/neurogenic diseases and other diseases incapable of being treated very well at present. A bag of the composition was brewed and taken once to twice per day with warm water.

Example 4: Composition 4

[0127] In this example, the total extract of Panax ginseng may be directly obtained from the extract of Panax ginseng purchased on the market, or the primary extract product of Panax ginseng.

TABLE-US-00008 Compatibility Dose Composition principle (g) Total extract of Panax ginseng Monarch drug 0.01 Wolfiporia cocos Ministerial drug 1.00 Nattokinase (powder) 1000 Fu Water-soluble and Guar gum Adjuvant drug 0.20 water-insoluble Alginic acid 0.20 dietary fiber Crude laminarin 0.20 Pericarpium citri 0.20 reticulatae Glucomannan 0.40 Psyllium seed husk 1.00 Siraitia grosvenorii Conductant drug 0.70

[0128] The above components were crushed, sieved and mixed well to prepare a unit amount of the composition 4 in the present invention. The composition 4 may replace the composition 1. The composition may exert two-way regulation on the types and functions of gut microbiota, thus improving and maintaining personalized gut microbiota diversity. Moreover, the composition may keep healthy and have treatment or prevention effects on chronic diseases in particular to metabolic diseases, immune diseases, mental/neurogenic diseases and other diseases incapable of being treated very well at present. A bag of the composition was brewed and taken once or twice per day with warm water.

Example 5: Composition 5

[0129]

TABLE-US-00009 Compatibility Dose Composition principle (g) Total extract of Panax ginseng Monarch drug 0.005 Wolfiporia cocos Ministerial drug 0.50 Nattokinase (powder) 500 Fu Water-soluble and Guar gum Adjuvant drug 0.1 water-insoluble Alginic acid 0.1 dietary fiber Crude laminarin 0.1 Pericarpium citri 0.1 reticulatae Glucomannan 0.2 Psyllium seed husk 0.5 Siraitia grosvenorii Conductant drug 0.35

[0130] The formula of this example may be used as an introducing prescription, or applied to the inadaptable patients, such as, patients accompanied with continuous abdominal distension, or stomachache after taking the composition 1 provided in Example 1 or the composition 4 provided in Example 4. The composition 5 may replace the composition 2 provided in Example 2. The composition may exert two-way regulation on the types and functions of gut microbiota, thus improving and maintaining personalized gut microbiota diversity. Moreover, the composition may keep healthy and have treatment or prevention effects on chronic diseases in particular to metabolic diseases, immune diseases, mental/neurogenic diseases and other diseases incapable of being treated very well at present. A bag of the composition was brewed and taken once or twice per day with warm water.

Example 6: Composition 6

[0131]

TABLE-US-00010 Compatibility Dose Composition principle (g) Total extract of Panax ginseng Monarch drug 0.02 Wolfiporia cocos Ministerial drug 2.00 Nattokinase (powder) 2000 Fu Water-soluble and Guar gum Adjuvant drug 0.4 water-insoluble Alginic acid 0.4 dietary fiber Crude laminarin 0.4 Pericarpium citri 0.4 reticulatae Glucomannan 0.8 Psyllium seed husk 2 Siraitia grosvenorii Conductant drug 0.70

[0132] The formula in the example is suitable for the patient whose feces is not improved obviously or improved slowly towards the intermediate type (type 4) of the Bristol Stool Scale after taking the composition 4 provided in Example 4. The composition 6 may replace the composition 3 provided in Example 3. The above components were crushed, sieved and mixed well to prepare a unit amount of the composition 6 in the present invention. The composition may exert two-way regulation on the types and functions of gut microbiota, thus improving and maintaining personalized gut microbiota diversity. Moreover, the composition may keep healthy and have treatment or prevention effects on chronic diseases in particular to metabolic diseases, immune diseases, mental/neurogenic diseases and other diseases incapable of being treated very well at present. A bag of the composition was brewed and taken once to twice per day with warm water.

Example 7: Composition 7

[0133] The composition was specified below: almond (0.25-1 g) and perilla seed (0.25-1 g) were added to the composition as an adjuvant drug. The composition 7 is suitable for the patient suffering gut microbiota imbalance and diagnosed with constipation due to intestinal dryness based on traditional Chinese medicine (TCM). The composition 7 may be used flexibly according to TCM diagnosis. The almond dietary fiber has a content greater than 10% and the abundant unsaturated fatty acids therein has the effect of lubricating the intestines. Perilla seed is rich in unsaturated fatty acids (>50%) and abundant essential amino acids. That is, perilla seed may provide substrates for gut microbiota, and also have the effect of lubricating the intestines and relaxing the bowels for constipation due to intestinal dryness.

[0134] The above components were crushed, sieved and mixed well to prepare a unit amount of the composition 7 in the present invention. The composition 7 is suitable for constipation patients. The composition may exert two-way regulation on the types and functions of gut microbiota, thus improving and maintaining personalized gut microbiota diversity. Moreover, the composition may keep healthy and have treatment or prevention effects on chronic diseases in particular to metabolic diseases, immune diseases, mental/neurogenic diseases and other diseases incapable of being treated very well at present. A bag of the composition was brewed and taken once or twice per day with warm water.

[0135] Ingredients for strengthening spleen and invigorating Qi include but not limited to a crude drug or extract of Panax ginseng and/or Panax quiquefolium.

[0136] The ingredient for clearing damp includes but not limited to a crude drug or extract of Wolfiporia cocos.

[0137] The ingredient for promoting the circulation of blood includes but not limited to a crude drug or extract of nattokinase or natto.

[0138] The water-soluble dietary fiber includes but not limited to one or more of glucomannan, pectin, alginic acid, β-glucan and inulin. Food ingredients or medicinal materials, or the like capable of extracting the above these components are certainly available.

[0139] The water-insoluble dietary fiber includes but not limited to one or more of cellulose, hemicellulose, and lignin.

[0140] In the daily dose (weight) of the composition, the water-soluble dietary fiber and the water-insoluble dietary fiber are calculated by total weight percentage of the composition, including 0.01-2 g crude drug of Panax ginseng and Panax quiquefolium, or 0.001-0.2 g extract of Panax ginseng and Panax quiquefolium, 0.1-5 g crude drug of Wolfiporia cocos, or 0.001-2 g extract of Wolfiporia cocos, 10-50 g natto powder, or 500-4000 Fu nattokinase; 0.1-3 g crude drug of Siraitia grosvenorii, or 0.001-0.2 g extract of Siraitia grosvenorii. The water-soluble dietary fiber accounts for 10%-70% by the total dose of the formula; the water-insoluble dietary fiber accounts for 10%-70% by the total dose of the formula.

[0141] The present invention is achieved by the following technical solutions: the technical solutions of the present invention are proved from four levels of molecule (gene analysis of intestinal bacteria), function (functional genomes analysis), system phenotype (Bristol Stool Scale), and some representative laboratory detection indexes, including blood lipid (total cholesterol, triglyceride, low density cholesterol and high density cholesterol), blood glucose (fasting blood-glucose, glucose tolerance test), serum uric acid, renal function indexes (serum creatinine and estimated glomerular filtration rate), and liver function indexes (alanine aminotransferase and serum aspartate aminotransferase). The composition may improve and maintain the personalized gut microbiota diversity via two-way regulation on gut microbiota, thus preventing or treating various diseases associated with gut microbiota imbalance.

[0142] The molecular level analysis was performed by OTU clustering and species annotation. Vsearchv2.4.4 was used for (OTU) analysis; the sequence was subjected to repetitive sequence removal (--derep_fulllength), clustering (--cluster_fast,-id 0.97) and chimera removal (--uchime_ref) (Rognes2016), then clustered into OTUs according to 97% similarity by default. Default parameters were used to select an OTU representative sequence; and the representative sequence was subjected to species annotation via VSEARCH based on SILVA128 database (Quastet al. 2013) to generate an OTU list, thus obtaining the community composition in each sample at the level of Phylum, Class, Order, Family, Genus and Species, as well as the abundance and classification of all the OTUs in each sample. For the quality control of the raw sequence data, the data size of the tags and clean tags was firstly judged whether of satisfying the sequencing requirements; generally, when the data size of the tags was up to 30,000 reads above, the sequencing requirements were satisfied. Reads of the mean clean tags of the 16 s sample in this test were 107670.08, completely capable of satisfying the sequencing requirements. OTUs whose content was lower than 0.001% of the total sequences in the sample were not taken in this experiment due to the current detection sensitivity.

[0143] For the functional genome analysis, the number of Species and Genus of the raw 16s sequencing data was standardized. A comparatively mature tool PICRUSt (PICRUSt Nature Biotechnology, 1-10. 8 2013) which is developed at the earliest and used for predicting microflora functions based on 16S rRNA gene sequence was then utilized to obtain the predictive functions of the genome.

[0144] As for the system phenotype analysis, Bristol Stool Chart, as shown in FIG. 1, was utilized as an integrated index of gut microbiota diversity for analysis to obtain Bristol Stool Score. The judgment method is as follows: the point of type 4 (normal faeces) is 1, the point of types 3 and 5 is 2, the point of types 2 and 6 is 4, the point of types 1 and 7 is 6. The higher the point is, the more abnormal the faeces is. Bristol Stool Scale is the best detection index to reflect the normality of the gut microbiota microecosystem in the level of body phenotype (Falony et al. Science 2016). The objective of the present invention is to prove that the composition may reconstruct the structure of gut microbiota via two-way regulation, thus promoting the Bristol Stool Score to transform towards the intermediate phenotype (type 4). That is, constipation may be eliminated and diarrhea may be improved instead of simply improving constipation or diarrhea.

[0145] Modified Cleveland Stool Score, as an auxiliary index of defecation, is also taken in the present invention. The method may be used to achieve better comprehensive analysis on the improvement effects on constipation based on the point of Bristol Stool Scale plus indexes listed in the two tables.

TABLE-US-00011 Point 0 Point 1 Point 2 Point 3 Point 4 Defecation times More than 3 Twice/week Once/week Once Once times/week below/week below/month Difficult defecation No Accidental* Sometimes* Often* Always* Feeling of residual feces No Accidental Sometimes Often Always Stomachache No Accidental Sometimes Often Always Defecation time 5 min below 5-9 min 10-19 min 20-29 min 30 min above Auxiliary defecation No Laxative Enema Desire to defecate, but no 0 1-3 4-6  7-9 More than 10 defecation Times/24 h times History of constipation 0 1-5 6-10 11-20 More than 21 (year) years *Accidental: once below/month; sometimes: once/more than one month-once below/week; often: once/more than one week-once below/day; always: more than once/day

[0146] The administration method, administration time, detection method and statistical treatment are concluded and specified as follows:

TABLE-US-00012 Sample size Detection/ Measurement (Male/ Medicament Administration Measurement Analysis Statistical index Female) Age taken* time (d) method method method 16s RNA 30 (20/10) 26- Compositions 14 16s RNA Gut Pearson sequencing 74 1-7 were sequencing microbiota correlation analysis of regulated analysis of types coefficient microorganism based on microorganism were was taken TCM classified to the diagnosis and according correlation, administration to the and non- reaction analysis correlation on the was excluded Operational by paired T Taxonomic test; paired Units T test was 30 (20/10) 26- 30 PICRUSt used for 74 analysis intergroup of 16S control rRNA gene sequence Bristol 28 (19/9) 26- 14 Self-observe Analysis was Paired T test Stool Scale 74 and report performed was used for 24 (17/7) 26- 30 according the difference 74 to the before and following after types of administration points: of intergroup Type control 4 = 1; types 1, 7 = 6; types 2, 6 = 4; types 3, 5 = 2 Modified 28 (19/9) 26- 14 Self-observe Quantitative Paired T Cleveland 74 and report analysis was test was Stool Scale 24 (17/7) 26- 30 performed used for the 74 on the basis difference of Bristol before and Stool Scale after and other administration defecation symptoms (the specific method is referring to the description in this text) *Administration method and time are specified as follows: 1) the composition 1 or 4 was taken first (in this example, the subsequent test data was obtained on the condition that the composition 1 was mixed with 250-300 ml warm water and taken twice per day as the starting formula). After taking the composition, some of patients would suffer abdominal distension and even stomachache, and the symptoms of abdominal distension and stomachache would be improved or removed within two or three days generally, and then, the composition may be continuously taken. 2) If the reaction of abdominal distension and even stomachache last a week around, the composition 2 or 5 was used for replacement (in this example, the subsequent test data was obtained on the condition that the composition 2 was taken as the adjustment formula). After the patient adapted to the composition one week later, if the condition of the feces (Bristol Stool Scale) was good, the composition 2 or 5 may serve as the maintenance prescription. If the condition of feces (Bristol Stool Scale) had no obvious response, the composition 1 or 4 was taken again once the abdominal distension or stomachache was improved or removed. 3) If the condition of feces (Bristol Stool Scale) had no obvious response with one week dosing of the composition 1 or 4, the composition 3 or 6 was used (in this example, the subsequent test data was obtained on the condition that the composition 3 was taken as the adjustment formula). If the condition of feces (Bristol Stool Scale) had good response, the composition 1 or 4 was taken again as the maintenance prescription .4) The patients accompanied with constipation started to take the composition 7. When the constipation was improved after administration, the composition 1 or 4 was taken as the maintenance prescription.

[0147] Moreover, it should be noted that in the table above, the subjects administered for 14 days and the subjects administered for 30 days were from the same group of patients. Feces of these subjects were tested twice to confirm the intervention effect of the composition on the subacute (14 days) and long-term (30 days) of gut microbiota. Meanwhile, repeatability of the drug effect was also verified by the comparison of the two test results.

[0148] The composition has good two-way regulation effect on Phylum, Class, Order, and Family. The so-called two-way regulation effect mainly refers that the composition may selectively enhance the relatively less abundant strain and their function. The two-way regulation effect is reflected in that the lower the relative abundance of the bacteria, or functional genomes is before administration, the higher the relative abundance of the bacteria, or functional genomes is after administration. The increase of the relatively less abundant intestinal bacteria or functional genomes proportionally lower the ratio of dominant bacteria or functional genomes, capable of strengthening and maintaining the microecological balance of gut microbiota. It will be abbreviated for two-way regulation in the following description of the present invention, and will be not repeated any more.

[0149] FIGS. 2a-2d respectively show correlation diagrams of relative abundance of bacteria before and after administration at the level of Phylum, Class, Order, and Family; (X-coordinate is the relative abundance before administration; Y-coordinate is the change rate of the abundance after administration, namely, relative abundance after administration/relative abundance before administration, for example, “1” indicates no change of the relative abundance after administration; “>1” indicates the increase of the relative abundance after administration; “<1” indicates the decrease of the relative abundance after administration; the dark spot represents the mean value of each bacterium at the level of Phylum, Class, Order, and Family). The left figure shows a correlation diagram with 14-day dosing. The right picture shows a correlation diagram with 30-day dosing.

[0150] As shown in FIG. 2a, at the level of Phylum, the lower abundance the bacterium is, the higher increment is observed after administration. with 14-day dosing, it has appeared an obvious negative correlation (the left figure of FIG. 2a), and there are remarkable statistical significances; with 30-day dosing (the right picture of FIG. 2a), the significant statistic differences are further increased. At the levels of Class (FIG. 2b), Order (FIG. 2c), and Family (FIG. 2d), there are obvious negative correlations with both 14-day (corresponding to the left figure) and 30-day (corresponding to the right picture) later after administration; and there are remarkable statistical significances. The above results indicate that the composition has good two-way regulation at the levels of Phylum, Class, Order and Family, and may inhibit the relative abundance of dominant bacteria and enhance the less abundant bacteria, thereby improving the functional balance and diversity of gut microbiota.

[0151] The composition has an inhibitory effect on the most dominant bacterium at the level of Phylum, Bac_Firmicutes. As shown in FIG. 3 (Y-coordinate is relative abundance; the transverse line in the box plot represents a median; X represents a mean value; straight lines at both ends represent a scope of 75%. Coordinates or charts in the subsequent FIG. 4, FIG. 5, FIG. 8, FIG. 9a, FIG. 9b, FIG. 9c, FIG. 12, FIG. 13b, FIG. 13c, FIG. 13d, FIG. 16, FIG. 17, FIG. 18, FIG. 20a, FIG. 20b, FIG. 21b, FIG. 24, FIG. 26b, FIG. 27, FIG. 29, FIG. 31, FIG. 33b, FIG. 34a, FIG. 34b, FIG. 35, and FIG. 36 have the meanings the same as those in FIG. 3). With 14-day dosing, the relative abundance of Bac_Firmicutes decreases 14.5%, and there are remarkable statistical significances. with 30-day dosing, the relative abundance of Bac_Firmicutes continuously decreases 15% above, and statistical significances are greater than that of the 14-day administration. The above result shows the effectiveness and long-term intervention effect of the composition. Obesity patients have increased Bac_Firmicutes, and the most effective bariatric surgery can decrease the abundance of Bac_Firmicutes (Muscogiuri et al. 2019; Ejtahed et al. 2018). It indicates that the composition may improve the body weight of patients, the frequently accompanied metabolic syndromes, type 2 diabetes (type II diabetes), fatty liver and the like by reducing the relative abundance of Bac_Firmicutes without highly-invasive surgery. The current researches believe that Bac_Firmicutes can ferment the dietary fiber incapable of being digested by human, thus providing extract energy sources for human being. This is one of the important contributions to help people get through famine in the hungry age. However, in the satiation/overfeeding age, such an action causes the side effect of overnutrition.

[0152] The composition significantly improves the abundance of the second dominant bacterium at the level of Phylum, Bac_Bacteroidetes. As shown in FIG. 4, the relative abundance of Bac_Bacteroidetes increases 13.8% with 14-day dosing. With 30-day dosing, the relative abundance increases to 15%, and there are remarkable statistical significances. The above result proves the effectiveness and long-term intervention effect of the composition. The relative abundance of Bac_Bacteroidetes decreases in obesity patients. The composition is expected to improve the body weight of patients, as well as frequently accompanied metabolic syndromes, or type 2 diabetes, fatty liver and the like by improving the relative abundance of Bac_Bacteroidetes (Muscogiuri et al. 2019). Moreover, Bac_Bacteroidetes in the patients with inflammatory bowel disease or Crohn's disease decreases significantly, which is one of the reasons to cause the imbalance of gut microbiota microecosystem (Presti at al. 2019). The composition may improve the abundance of Bac_Bacteroidetes, and used for a medicament or a health-care product or food, and may be expected to treat and prevent the chronic inflammatory bowel diseases caused by immunologic dysfunction.

[0153] The composition significantly improves the abundance of the third dominant bacterium at the level of Phylum, Bac_Proteobacteria. As shown in FIG. 5, the relative abundance of Bac_Bacteroidetes increases 23.9% with 14-day dosing. With 30-day dosing, the relative abundance increases 41% above, and there are remarkable statistical significances. The above result proves the effectiveness and long-term intervention effect of the composition.

[0154] The composition may improve the abundance of other less abundant bacteria at the level of Phylum. As shown in FIG. 6 (X-coordinate is relative abundance). For most of the less abundant bacteria at the level of Phylum above the detection limit, the relative abundance is improved with 14-day dosing, including 214.15% Bac_Actinobacteria, 276.83% Bac_Fusobacteria, 264.62% Bac_Verrucomicrobia, 169.6% Bac_Synergistetes, 154.25% Bac_Epsilonbacteraeota, 135.36% Bac_Patescibacteria, and 140.67% Bac_Lentisphaerae. In the above less abundant bacteria at the level of Phylum, the relative abundance of Bac_Actinobacteria and Bac_Fusobacteria may help enhancing immunity or increasing the therapeutic effects of anti-cancer drugs (Helmink et al. Nature Medicine 2019). The composition may enhance immunity or increase the perceptibility of the host human body to anti-cancer drugs by enhancing these less abundant bacteria at the level of Phylum.

[0155] As shown in FIG. 7 (X-coordinate is relative abundance). with 30-day dosing, the same trend is kept: 152.14% Bac_Actinobacteria, 271.65% Bac_Fusobacteria, 251.06% Bac_Verrucomicrobia, 131.05% Bac_Tenericutes and 138.46% Bac_Synergistetes. The above results prove the effectiveness and long-term intervention effect of the composition on the less abundant bacteria at the level of Phylum.

[0156] To sum up, the composition may inhibit the relative abundance of dominant bacteria and enhance the relative abundance of the less abundant bacteria (or relatively less abundant dominant bacteria) at the level of Phylum, and shows good two-way regulation. The enhancement of the less abundant bacteria at the level of Phylum indicates that the composition may help the reproduction and maintenance of low-abundance bacteria, thus helping improving and maintaining the diversity of gut microbiota, and keeping the health condition of the gut microbiota microecosystem.

[0157] As shown in FIG. 8 (Y-coordinate represents a Bac_Bacteroidetes/Bac_Firmicutes ratio), the composition improves the Bac_Bacteroidetes/Bac_Firmicutes ratio. With 14-day dosing, the composition increases the median of the Bac_Bacteroidetes/Bac_Firmicutes ratio by 5%. With 30-day dosing, the median even increases to 10%, and there are remarkable statistical significances. The above result proves the effectiveness and long-term intervention effect of the composition. The increase of the Bac_Bacteroidetes/Bac_Firmicutes ratio may improve the metabolic functions of the host, and particularly have useful effects on obesity and diabetes, which have been proved by multiple researches and clinical observations (Qin J. at al., Nature 2010; Karlsson F H, Nature 2013). The composition may improve the metabolic diseases by adjusting the Bac_Bacteroidetes/Bac_Firmicutes ratio.

[0158] Gut-brain axis is an existing concept. The research progress on gut microbiota brings new contents for such a concept. For example, autism is always accompanied with digestive tract symptoms such as, constipation and partial eclipse and thus, has been concerned extensively in the correlation with gut microbiota for the past few years. The latest shocking discovery has proved that the decrease of several specific bacterial genus, including Bacteroides and Parabacteroides, and the increase of Lachnospriraceae are the reasons (causative) to cause abnormal behaviors of autism (Sharon et al. Cell 2019). The composition may significantly decrease the relative abundance of Lachnospriraceae (FIG. 9a), and simultaneously increase the relative abundance of Parabacteroides (FIG. 9b) and Bacteroides (FIG. 9c). It indicates that the composition is expected to improve the symptoms of autism from the cause of disease. The composition is used for a medicament or a health-care product or food, and may have treatment and prevention effects on autism and other diseases caused by gut-brain axis dysfunction.

[0159] Researches show that compare to the composition of bacteria, there is always a smaller inter-individual functional variation, which may reflect the condition of the gut microbiota microecosystem better. The present invention further specifies the effects of the composition from the functional level by analyzing the functional genomes of gut microbiota. FIG. 10 (X-coordinate is the relative abundance before administration, and Y-coordinate the change rate of the relative abundance after administration; the filled dots in the figure show mean values of metabolic pathways) shows the related analysis results of the changes of the general functional metabolic pathways (213 pathways in total) after administration (the left figure shows the result with 14-day dosing, and the right picture shows the result with 30-day dosing) and the relative abundance before administration; the dotted line in the figure represents a linear trend. As shown in the figure, the composition of the present invention shows excellent two-way regulation effects; the correlation coefficient is −0.9 around, and there is a highly significant negative correlation (p=0.000). Such a result proves that the composition has two-way regulation on the overall metabolic pathways, thus showing its usefulness in the aspects of improving, strengthening and maintaining the functional balance and diversity of gut microbiota from the overall level.

[0160] The present invention further performs in-depth studies on the usefulness of the composition from the following four aspects. Firstly, from the angle of core function of gut microbiota, namely, maintaining self-survival and reproduction by bacteria, FIGS. 11-18 indicate the acceleration of the composition on self-viability of gut microbiota; secondly, FIGS. 19-20 indicate that the composition may enhance the catabolism of gut microbiota to pollen hazardous substances, thus assisting or promoting the health of the host human body; thirdly, FIGS. 21-33b indicate that the composition may promote the gut microbiota to increase the metabolites beneficial to the host human body; finally, FIGS. 34a-38 indicate that the composition may adjust the metabolic genomes of gut microbiota, thus promoting the immune metabolism functions.

[0161] As shown in FIG. 11 (X-coordinate is the relative abundance before administration, and Y-coordinate is the change rate of the relative abundance after administration; the filled dots in the figure show mean values of the relative abundance of related genome; the dotted line represents a linear trend), the cellular process summarizes the basic survival functions of gut microbiota, including genetic transcription, cell signal transduction, function and metabolism of mitochondria, and the like. There is certain negative correlation with 14-day dosing (left figure), and the correlation is more obvious with 30-day dosing (right picture), and there are remarkable statistical significances. The dotted line in the figure represents an exponential trend. The composition has a very strong acceleration effect on the least abundant compare to pre-administration regardless of 14- or 30-day dosing. It indicates that the composition has two-way regulation on the cellular process.

[0162] FIG. 12 (Y-coordinate represents the relative abundance) indicates that the composition has acceleration on the cell nucleus gene transcription, a subordinate concept of the cellular process. with 14-day dosing (left figure), there is an accelerating trend to the relative abundance of the transcription related proteins gene group; and with 30-day dosing, such kind of acceleration is up to remarkable statistical significance, thus indicating the effectiveness of the composition, in particular to long-term administration.

[0163] FIGS. 13a-13d (Y-coordinate of FIG. 13a represents the change rate of the relative abundance before and after administration; X-coordinate represents the relative abundance before administration; the dotted line represents a linear trend. Y-coordinates of FIG. 13b-13d represent the relative abundance) indicate the acceleration of the composition on the cytomembrane information transport function, a subordinate concept of the cellular process. The composition has a very strong enhancement effect on the least abundant cytomembrane information transport function genes (Membrane Transport Gene Group) by both 14- and 30-day dosing. It indicates that the composition has two-way regulation on the cytomembrane information transport function. Relevant analysis indicates that the composition has two-way regulation on the cytomembrane information transport function, which is mainly reflected in that the relatively less abundant electron transfer carriers genome, inorganic ion transport genome and pores ion channels genome are enhanced very well. A trend and a statistical significance were observed in groups with 14- and 30-day dosing, respectively. Such an effect may strengthen the cell information transport of less abundant bacteria or flora to enhance their survival and reproduction capacity.

[0164] The cellular process includes repair and replication functions of DNA. As shown in FIG. 14 (X-coordinate is the relative abundance before administration, and Y-coordinate is the change rate of the relative abundance after administration; the filled dots in the figure show mean values of the relative abundance of related genome; the dotted line represents an exponential trend). Even though the statistical correlation analysis only shows a weak negative correlation, it can be seen from the figure that the relative abundance of the non-homologous end-joining (with the least abundance) increases by 60% after 14 and 30 days administration. The result indicates the effectiveness of the composition on the less abundant functional genome. Non-homologous end-joining is a kind of special DNA double-strand break repair mechanism that eukaryotic cells link two DNA broken ends with each other independent of DNA homology. The results show that the composition may accelerate eucaryon, also may including intestinal bacteria to use the non-homologous end-joining repair mechanism for DNA repairing and regeneration.

[0165] As shown in FIG. 15 (X-coordinate is the relative abundance before administration, and Y-coordinate is the change rate of the relative abundance after administration; the filled dots in the figure show mean values of the relative abundance of related genome; the dotted line represents a linear trend), the composition also shows a good negative correlation to the life-maintaining functional genome (cell growth and death-related genome) of gut microbiota, and has two-way regulation effects.

[0166] The cellular process includes cell apoptosis and protein degradation through Ubiquitin system. As shown in FIG. 16 (Y-coordinate represents relative abundance), the composition of the present invention may accelerate the process of cell apoptosis. Apoptosis is a process of programmed cell death to maintain the stability of internal environment. Impairment of apoptosis will cause lots of undesirable consequences, the typical one is abnormal cell proliferation, for example, cancer. The acceleration of the composition on cell apoptosis may maintain the normal turnover of cells.

[0167] Ubiquitin system is another cell protein degradation chain reaction. Ubiquitin system participates in most of the short-period protein degradation, and participates in lots of cell life processes by regulating the metabolism of intracellular proteins. FIG. 17 (Y-coordinate shows the relative abundance) indicates that the composition may improve the ubiquitin system-related genome with 14-day dosing. It indicates that the composition of the present invention has a functional acceleration trend to the ubiquitin system, and with 30-day dosing, the acceleration effect is further enhanced and has remarkable statistic differences compared with that before administration. The above result indicates a long-term intervention effect of the composition.

[0168] Peptidoglycan is an important component of bacterial cell wall. The composition shows certain two-way regulation on Glycan Biosynthesis. As shown in FIG. 18 (Y-coordinate shows the relative abundance), with 14- and 30-day dosing, the relative abundance of glycan biosynthesis-related genome is increased; after taking the composition of the present invention, the glycan biosynthesis shows an increase trend.

[0169] Xenobiotics biodegradation is an important function to gut microbiota. Xenobiotics include medicaments, pesticides, plastics or rubber residues, environmental pollutants, food additives, and the like; most of them are harmful to human health. As shown in FIG. 19 (X-coordinate is the relative abundance before administration, and Y-coordinate is the change rate of the relative abundance after administration; the filled dots in the figure show mean values of the relative abundance of related genome; the dotted line represents an exponential trend), the composition may bidirectionally adjust the biodegradation of gut microbiota to xenobiotics. Statistics show that there are significant negative correlations with 14- or 30-day dosing. The fine dotted line shows the acceleration of the composition on less abundant functional genome. Such kind of selective acceleration is of significance to human health.

[0170] The table below summarizes the acceleration effects of the composition on some important functional genomes of xenobiotics biodegradation. These xenobiotics include DDT raw materials, the level-I cancerogenic substance, Dioxin, and atrazine, the herbicide applied most widely in the world, and the like.

TABLE-US-00013 Name of the Increment rate biodegradable 14-day 30-day compound Effect of the compound dosing dosing Fluorobenzoate Pesticide or medical intermediate 229.1% 202.8% Chlorocyclohexane Pesticide, rubber antiscorching agent, 161.8% 122.8% or medical intermediate Chlorobenzene Synthetic raw material of DDT; solvent 161.8% 122.8% of ethyecellulose and lots of resins, and other intermediates of benzene series Caprolactam Raw material of nylon plastic 285.2% 198.2% Styrene Important monomer of synthetic resins, 135.8% 122.4% ion exchange resins and synthetic rubbers and the like; styrene has been classified as category-2B carcinogen by WHO Atrazine The herbicide applied most widely in the 167.5% 120.6% world. Atrazine endangers mammal via endocrine disruption, genotoxicity, reproductive toxicity and the like. Atrazine has been listed a possible cancerogenic substance by Environmental Protection Agency (EPA) Dioxin Dioxin is a kind of colourless, odourless, 135.1% 116.5% and highly toxic liposoluble substance. Dioxin is highly toxic and exists in the air, soil and water with fine particles. Dioxin has been listed the level-I cancerogenic substance by International Agency for Research on Cancer. Aminobenzoate The purest aromatic aminocarboxylic acid 133.1% .sup. 112% Xylene Xylene is widely applied in the industries 127.2% 111.9% such as, coatings, resins, dyestuff and printing ink as a solvent. Xylene has been classified as category 3 carcinogen by WHO Note: in the table above, the calculation method of the increment rate of each biodegradation-related genome is as follows: [(relative abundance of the genome with 14- or 30-day dosing/relative abundance of the genome before administration) × 100].

[0171] FIGS. 20a-20b (Y-coordinate represents the relative abundance) indicate that the composition has acceleration on a cytochrome p450 (Cyp450). Cyp450 can reduce or eliminate the bioactivity of xenobiotics, thus promoting them to be discharged from human body. From the analysis on the functional genomes of Cyp450 with the functions of Drug Metabolism (FIG. 20a) and Xenobiotics Metabolism (FIG. 20b), it can be seen that there is an accelerating trend with 14-day dosing, and the acceleration effect has statistical significances after 30 days administration. Increased Cyp450 function may be the major mechanism to accelerate the biodegradation of the above xenobiotics, including drugs, pesticides, environmental pollutants, and food additives, and the like.

[0172] FIG. 21a (X-coordinate is the relative abundance before administration; Y-coordinate is the relative abundance after administration; the dotted line represents an exponential trend) and FIG. 21b (Y-coordinate is the relative abundance) show that the composition has two-way regulation on the biosynthesis of polyketides and terpenoids. The decrease of the correlation coefficient with 30-day dosing is caused by the increase of the variation coefficient due to the sharp increase (>1100%) of the type II polyketide products. Polyketides are a category of secondary metabolites produced by bacteria, fungi, plants and animals. Due to its important bioactivity, polyketides can serve as antibiotics (e.g., erythromycin), antifungal agents (e.g., amphotericin), anti-cancer drugs (e.g., doxorubicin), immunosuppressants (e.g., rapamycin), anti-parasitic agents, and the like. Terpenoids are generic terms of a series of terpenoid compounds; the total number of the existing terpenoid compounds has exceeded 22,000 currently. Lots of terpenoid compounds have important physiological activity, and are a comparatively important category of compounds in Chinese herbal medicines, for example, tanshinones compounds, triptolide, stevioside, and rographolide, and the like. Moreover, there are further Yuanhuacin, Schisantherin and other diterpenoids ingredients with antitumor activity. These products not only have protective effects on gut microbiota, but also may provide bioactive ingredients beneficial to the host human body. What's more, as shown in the dotted line of FIG. 21a, the composition has a selective enhancement trend to less abundant genetic groups, and may promote the synthesis of the relatively scarce polyketides and terpenoids.

[0173] As shown in FIG. 22 (X-coordinate is the relative abundance before administration, and Y-coordinate is the change rate of the relative abundance after administration; the filled dots in the figure show mean values of the relative abundance of related genome; the dotted line represents an exponential trend), the composition has two-way regulation on cofactors and vitamins, and has stronger acceleration to the less abundant genetic groups. The composition is expected to promote and maintain the physiological functions of the host human body by adjusting the relatively scarce cofactors and vitamins.

[0174] As shown in FIGS. 23a-23c (x-coordinate is the relative abundance before administration, and Y-coordinate is the relative abundance after administration; the dotted line represents a linear trend), the composition has good two-way regulation on the vitamins B synthesis-related functional genomes, including vitamins B1 (left figure of FIG. 23a), B2 (right figure of FIG. 23a), B6 (left figure of FIG. 23b), folic acid (B9) (right figure of FIG. 23b), and B12 (FIG. 23c). Vitamins B need to be cooperated with each other to work. Therefore, the overall improvement of the composition on the relatively less abundant functional genomes is of important meaning to maintain and improve the physiological functions of the overall vitamins B.

[0175] FIG. 24 (Y-coordinate is the relative abundance of the lipoic acid metabolism-related genome) shows that the composition has acceleration on the cofactor lipoic acid. with 14-day dosing, the composition shows an improvement trend, and with 30-day dosing, there are remarkable statistical significances. Lipoic acid has a strong antioxidation and can relieve the risk to fatty liver and hyperlipidemia, as well as the toxicity of heavy metals on other cofactors.

[0176] As shown in FIG. 25 (X-coordinate is the relative abundance before administration, and Y-coordinate shows a change of the relative abundance after administration; the filled dots in the figure show mean values of the relative abundance of related genome; the dotted line represents an exponential trend), the composition has two-way regulation on the carbohydrate metabolism-related functional genomes (Carbohydrate Metabolism Gene Group) and shows an enhancing effect on the less abundant functional groups.

[0177] As shown in FIG. 26a (X-coordinate is the relative abundance before administration, and Y-coordinate is the change rate of the relative abundance after administration; the filled dots in the figure show mean values of the relative abundance of related genome; the dotted line represents an exponential trend), the composition has two-way regulation on the lipid metabolism. Statistical analysis indicates that there is a trend of negative correlation with 14- or with 30-day dosing. As shown in the trend represented by the dotted line, the composition has a very strong acceleration on some extremely less abundant functional genomes. Lipid includes important components (phospholipid) of cytomembrane, important physiological regulation substances (including lipid-soluble vitamins), and important intermediates of biological metabolism, and the like, which provides important material basis for vital activity. As shown in the box plot (26b), the regulation effect of the composition on tissue metabolism may be partially achieved by increasing the bile secretion.

[0178] As shown in FIG. 27 (Y-coordinate represents the relative abundance), the composition significantly improves the abundance of the linolenic acid synthesis and metabolism functional genomes (Linolenic Acid Metabolism). With 14-day administration, there is an enhancement trend, and with 30-day dosing, there are remarkable statistic differences, indicating the long-term effectiveness of the composition. Linolenic acid is a kind of ω-3-series polyenoic fatty acid, and is an important component to constitute human tissue cells, and can be synthesized, metabolized and transformed into DHA and EPA essential to human body. Linolenic acid cannot be synthesized in human body, and one of the sources is gut microbiota synthesis. The shortage of linolenic acid in human body will cause lipid metabolism disorders, resulting in immunity decrease, amnesia, fatigue, hypopsia, cardiovascular and cerebrovascular diseases, and the like. Moreover, linolenic acid is also an important cosmetic.

[0179] As shown in FIG. 28 (X-coordinate is the relative abundance before administration, and Y-coordinate is the change rate of the relative abundance after administration; the filled dots in the figure show mean values of the relative abundance of related genome; the dotted line represents an exponential trend), the technical solution of the present invention has significant two-way regulation on the functional genomes associated with amino acid synthesis and metabolism. The composition has a stronger effect on the less abundant functional genomes associated with amino acid synthesis and metabolism with 14- and 30-day dosing.

[0180] As shown in FIG. 29 (Y-coordinate is the relative abundance), the composition has certain acceleration on the relative abundance of the functional genomes associated with tryptophan metabolism. Tryptophan is a kind of precursor to neurotransmitter, serotonin. Because serotonin cannot pass through blood brain barrier by itself, peripheral blood has to be utilized such that serotonin enters the intracerebral precursor synthesis. The shortage of serotonin will cause the shortage of intracerebral serotonin. Brain serotonin is a key neurotransmitter to maintain the internal drive (appetite, sleep and sex) and emotion. The decrease of serotonin level is the major reason to cause down in spirits, depression, and manic-depressive psychosis, and may be closely related to chronic fatigue diseases, and fibromyalgia, and the like.

[0181] Besides the precursor as shown in FIG. 29, the composition has certain two-way regulation on related functional genomes to serotonin (5-HT). As shown in FIG. 30, X-coordinate of the left figure shows the relative abundance of the genetic group associated with serotonin biosynthesis before administration; Y-coordinate shows a change rate of the relative abundance after administration; the dotted line shows a linear trend. X-coordinate of the right figure shows changes of the relative abundance of the group before administration and the group with 30-day dosing, and Y-coordinate shows the relative abundance. Each line in the right figure represents a change of the relative abundance of each patient before and after administration; Pre represents the relative abundance before administration; and the right shows the increase of the relative abundance after administration. It can be seen from the table on the right of FIG. 30 that for the patient with lower relative abundance before administration (relative index is ≤16), the relative abundance is significantly improved after administration (the right of FIG. 30). Serotonin cannot pass through blood brain barrier by itself; the serotonin synthesized by gut microbiota mainly acts on end visceral organs, in particular to digestive system. Currently, the existing serotonin is related to the control of gastrointestinal peristalsis, sensitivity and secretion, and may adjust the functions of the gastrointestinal and digestive system.

[0182] Lysine is one of the essential amino acids to human and mammal, cannot be synthesized by the body itself and has to be supplemented from the outside. Gut microbiota has the genes to synthesize lysine. As shown in FIG. 31 (Y-coordinate is the relative abundance), the composition may increase the relative abundance of the functional genomes associated with lysine metabolism with 14 or 30-day dosing. Lysine is easily broken and short and thus, is called the first limiting amino acid. Lysine has important nutritional significances in the aspects of human growth and development, enhancement of body immunity, antiviral action, promotion of fat oxidation, and relief of anxiety, and the like.

[0183] As shown in FIG. 32 (X-coordinate is the relative abundance before administration, and Y-coordinate is the change rate of the relative abundance with 30-day dosing; the dotted line represents a linear trend), with 30-day dosing, the composition has two-way regulation on the functional genomes associated with short-chain fatty acid synthesis and metabolism. Short-chain fatty acids mainly include acetic acid, propionic acid and butyric acid. The composition has two-way regulation on the functional genomes associated with acetic acid and butyric acid synthesis and metabolism. The composition also has certain two-way regulation on the functional genomes associated with propionic acid synthesis and metabolism. Acetic acid is the most effective agonist to the receptor GPR43, and can promote the ileum endocrine cells, L cells to secrete glucagon-like peptide-1 (GLP-1), control inflammatory response and the like, and has multiple aspects of physiological activity. It should be emphasized that EC50 of acetic acid to GPR43 is 250 μM to 500 μM, while the mean concentration scope of acetic acid in colon cavity is 10-100 mM; calculated by the mean concentration of acetic acid, GPR43 and ligand should be always saturated. However, as shown in FIG. 32, for the individual whose relative abundance is close to 0, colon has a thick mucus layer; therefore, the continuous mucus flow and creep result in a concentration gradient of acetic acid; the acetic acid concentration in these subjects is not enough to activate the GPR43 receptor. This is the important physiological significance for the composition to enhance the relatively less abundant functional genomes. Butyric acid mainly includes the following major functions, namely, providing energy for colonic epithelial cells, inhibiting histone deacetylase (HDACs), anti-inflammatory or immune modulating function (Makki K et al., Cell Host Microbe. 2018; Koh A et al., Cell, 2016). The composition is of important meaning to solve the butyric acid shortage of these people with low relative abundance.

[0184] As shown in FIG. 33a (X-coordinate is the relative abundance before administration, and Y-coordinate is the change of the relative abundance after administration; the filled dots in the figure show mean values of the relative abundance of related genome; the dotted line represents an exponential trend), the composition has two-way regulation on the internal secretion functional genomes. There are remarkable statistical significances with 14- and 30-day dosing, in particular to the extremely less abundant melanogenesis-related functional genomes, and the relative abundance increases to 1.6-1.7 times. Melanin in skin can absorb ultraviolet ray to prevent it from penetrating into the deep part of skin and from damaging tissue cells, thus achieving a protective effect.

[0185] FIG. 33b (Y-coordinate represents the relative abundance) indicates that the composition has acceleration on biosynthesis of steroid hormones. Steroid hormones are approximately divided into five types: glucocorticoid, mineralocorticoid, as well as estrogen, progestogen and androgen of sex hormones. Glucocorticoid and mineralocorticoid relate to wide physiological systems such as, inflammation control, carbohydrate metabolism, protein metabolism, blood electrolyte level and immunoreaction. Low sex hormone will cause developmental retardation of primary/secondary sex characters of children and adolescents, abnormality of female physiological cycle and gestation period, osteoporosis caused by postmenopausal female, male and female sexual hypofunction, and climacteric syndrome, and other associated diseases.

[0186] Gut microbiota plays a decisive role to the maturity of the host human body immune system and function maintenance. As foreign bodies, gut microbiota needs to be monitored by immune system; but as a mutualistic group, gut microbiota cannot be attacked by human immune cells. Such kind of balance actually plays the role of training body's immune system to recognize harmful and innocuous exogenous substances. Gut microbiota are vividly compared to the accelerator and brake to control the host, the body's immune system by Justin L. Sonnenberg, a professor of Stanford University. At present, the most important problem is hypofunction of the brake, the light one suffers food or pollen allergy, for the serious one, immune cells will attack tissues of the body. Lipopolysaccharide (LPS) plays a crucial role to the accelerator and brake during the interaction between gut microbiota and the host body's immune system. LPS acts on the pattern recognition receptor of Toll-like receptors (TLRs). LPS promotes the development and maturity of the host body's immune system by the TLR4 receptor existing in target cells and plays the role similar to an accelerator. Meanwhile, LPS possessed by gut microbiota also plays a crucial role in adjusting the brake functions of immune system. Such a function is mainly achieved by activating the regulatory T cells to control the activity of immune system (Belkaid Y et al., Cell 2014; Tokuhara D et al., Allergology Int. 2019). The decrease of regulatory functions will cause immunologic dysfunction, and is closely related to the attack of various allergic diseases, such as food/drug/pollen body allergy, eczema; and autoimmune diseases, such as type-I diabetes, irritable bowel syndrome, inflammatory bowel disease, Crohn's disease, multiple sclerosis, rheumatoid, asthma and cancer. FIGS. 34a and 34b (Y-coordinate represents the relative abundance) indicate that the composition may significantly improve the relative abundance of LPS Biosynthesis Gene Group, and the relative abundance of functional genomes associated with LPS Biosynthesis Proteins, and may help adjusting the immunity of the host human body within the normal range.

[0187] FIG. 35 (Y-coordinate represents the relative abundance) indicates that the composition has acceleration on the extremely less abundant bacterium Pantoea (at the level of Genus). Currently, Pantoea lipopolysaccharide is orally taken or applied on skin, which may activate macrophage in vivo to have good effects on various diseases, including hyperlipidemia, diabetes, and atropine dermatitis (Nakata K et al., Food Sci Nutr. 2014). The composition has acceleration on Pantoea to further show the regulating effect thereof on immunity, and usefulness to immune diseases.

[0188] Natural immune system is an important line of defense for human body to resist pathogen invasion. Innate immunity further has RIG-I like Receptors (RLRs) besides the above pattern recognition receptor of Toll-like Receptors (TLRs). RIG-I belongs to RLRs. Interferon is triggered for expression after detecting the 5′-triphosphoric acid double-stranded RNA (5′ppp-dsRNA) in cells derived from virus, thus inhibiting the virus infection. FIG. 36 (Y-coordinate represents the relative abundance) shows the effect of the composition on RLRs. The composition shows an improvement trend to functional genomes associated with RLRs activity with 14-day dosing, and with 30-day dosing, there are remarkable statistical significances, indicating the long-term intervention effect of the composition.

[0189] Bristol Stool Score is utilized in this present invention as an integrated index of gut microbiota diversity to analyze the effect of the composition from the system level. It can be seen from observation in human body that the composition has significant two-way regulation. As shown in FIG. 37 (Y-coordinate shows the change of the Bristol Stool Score), the types of the Bristol Stool indicate that the composition may promote the faeces to converge towards type 4. with 14-day dosing, the composition shows an improvement trend, and with 30-day dosing, there are remarkable statistical significances. The composition is proved to improve and maintain the gut microbiota diversity and have a long-term intervention effect from the phenotype level. As a kind of physical symptom, defecation also shows that the composition has two-way improvement effects on the symptoms of feces, including constipation or diarrhea.

[0190] The Cleveland Stool Score improved on the basis of the Bristol Stool Score also shows obvious improvement effects. As shown in FIG. 38 (Y-coordinate shows the change of the Modified Cleveland Stool Score), there are remarkable significant statistic differences with 14-day dosing, and with 30-day dosing, the significant therapeutic effect is persistent. The composition is further proved to improve and maintain the gut microbiota diversity and have a long-term intervention effect from the phenotype level.

[0191] To further prove the improvement effect of the composition on body functions, representative laboratory detection indexes directed to some volunteers suffering from hyperglycemia, dyslipidemia or high serum uric acid were detected. These indexes include blood lipid (serum total cholesterol, serum triglyceride, serum low density lipoprotein cholesterol, serum high density lipoprotein cholesterol), blood glucose (fasting blood-glucose and glucose tolerance test), serum uric acid, renal function indexes (serum creatinine, estimated glomerular filtration rate), and liver function indexes (serum alanine aminotransferase and serum aspartate aminotransferase).

[0192] The administration method was the same as that for the volunteers with gut microbiota detection. Administration method is briefly specified as follows: 1) the composition 1 or 4 was taken first (in this example, the subsequent test data was obtained on the condition that the composition 1 was mixed with 250-300 ml warm water and taken twice per day as the starting formula). After taking the composition, some of patients would suffer abdominal distension and even stomachache, and the symptoms of abdominal distension and stomachache would be improved or removed within two or three days generally, and then, the composition may be continuously taken. 2) If the reaction of abdominal distension and even stomachache last a week around, the composition 2 or 5 was used for replacement (in this example, the subsequent test data was obtained on the condition that the composition 2 was taken as the adjustment formula). After the patient adapted to the composition one week later, if the condition of the feces (Bristol Stool Scale) was good, the composition 2 or 5 may serve as the maintenance prescription. If the condition of feces (Bristol Stool Scale) had no obvious response, the composition 1 or 4 was taken again once the abdominal distension or stomachache was improved or removed. 3) If the condition of feces (Bristol Stool Scale) had no obvious response one week later after taking the composition 1 or 4, the composition 3 or 6 was used (in this example, the subsequent test data was obtained on the condition that the composition 3 was taken as the adjustment formula). If the condition of feces (Bristol Stool Scale) had good response, the composition 1 or 4 was taken again as the maintenance prescription. 4) The patients accompanied with constipation started to take the composition 7. When the constipation was improved after administration, the composition 1 or 4 was taken as the maintenance prescription. The administration time is one month; other indexes were detected with 30-day dosing except the glucose tolerance test was performed once respectively with 14- and 30-day dosing.

[0193] Statistical treatment: Pearson correlation coefficient was taken to the correlation, and non-correlation was excluded by paired T test. As for the intergroup control, paired T test was used to compare the change before and after administration (p<0.05 shows significant differences).

[0194] <Improvement Effect on Dyslipidemia>

[0195] Test Method:

[0196] The volunteers were divided into a normal group and an abnormal group according to the Third Report of the National Cholesterol Education Program (NCEP), NIH Publication No. 02-5215. The volunteers received blood examination before administration and with 30-day dosing. The volunteers were forbidden to take any food except drinking water after 21:00 the previous night of the examination. Serum cholesterol was subjected to conventional determination via a cholesterol oxidase method, and triglyceride was subjected to conventional determination via a GPO-PAP enzyme method in a hospital laboratory.

[0197] Test indexes of the normal and abnormal blood are shown in the table below respectively:

TABLE-US-00014 Blood index Normal group Abnormal group Total cholesterol (TC) <5.172 mmol/L ≥5.172 mmol/L Low density lipoprotein <2.586 mmol/L ≥2.586 mmol/L cholesterol (LDL-C) High density lipoprotein ≥1.03 mmol/L <1.03 mmol/L cholesterol (LDL-C) Triglyceride (TG) <1.69 mmol/L ≥1.69 mmol/L

[0198] <Effect on Serum Total Cholesterol>

[0199] Table for basic information of the 30 volunteers (16 in the normal group and 14 in the abnormal group) and data change before and after administration

TABLE-US-00015 Serum total cholesterol (mmol/L) Normal group Abnormal group Before After Before After Name Age Gender administration administration Name Age Gender administration administration WXF 36 Male 4.07 3.87 DYF 55 Female 5.79 5.03 LWY 58 Female 4.35 6.80 ZYZ 40 Male 7.31 5.95 NJY 48 Male 5.14 3.16 ZHY 57 Female 6.07 4.11 WQL 61 Female 5.11 4.04 JZX 71 Female 6.44 4.15 WX 46 Male 3.83 3.71 CJY 44 Male 5.72 4.88 ZGC 53 Male 4.76 4.70 YWJ 67 Male 5.74 5.29 ZTH 20 Male 3.72 3.10 WHZ 53 Female 6.55 6.16 XDZ 25 Male 4.91 4.11 XMJ 57 Female 6.73 6.6 YHQ 46 Male 4.62 6.10 ZZM 51 Male 5.86 5.54 HCL 62 Male 3.31 3.19 LZZ 58 Male 5.79 5.01 XJF 58 Female 3.54 4.28 ZHX 41 Male 5.41 5.43 CXF 47 Male 4.01 4.03 WXY 41 Male 9.64 9.33 SJF 46 Male 5.03 4.53 WNL 62 Male 5.51 5.61 LMS 57 Male 3.61 3.03 LFG 73 Female 5.66 5.87 ZBK 22 Male 4.83 4.53 CLZ 38 Female 5.07 4.48

[0200] FIG. 39a shows the effect of the composition on the total cholesterol. Y-coordinate represents the concentration of serum total cholesterol. The left figures show the effect of the composition on the abnormal total cholesterol group. The composition may obviously decrease the concentration of the serum total cholesterol, and there is a significant statistic difference (p=0.0058). The right figure shows no obvious effect of the composition on the normal total cholesterol group. The abnormal elevation of serum cholesterol is closely associated with arteriosclerosis, heart disease, stroke and other types of cardiovascular and cerebrovascular diseases (Stamler, J. et al. JAMA, 1986; Keys A. et al. Am. J. Epidemiol. 1986). Meanwhile, cholesterol is an important raw material to synthesize physiological activators such as, adrenal cortical hormone, sex hormone and other important hormones, bile acid and vitamin D demanded by fat digestion and absorption, and also an important component to constitute cytomembrane, and is an important physiological activator to maintain viscera and tissue functions of human body. The action characteristic of the composition is to specifically decrease the abnormally elevated total cholesterol, but not influence the cholesterol concentration at the normal physiological level.

[0201] <Effect on Low Density Lipoprotein Cholesterol and High Density Lipoprotein Cholesterol>

[0202] Serum total cholesterol is the sum of cholesterol contained in lipoprotein of blood, and mainly consists of low density lipoprotein cholesterol and high density lipoprotein cholesterol. The therapeutic effects of 30 volunteers (12 in the normal low density lipoprotein cholesterol group and 18 in the abnormal low density lipoprotein cholesterol group) were observed in this present invention. Table for basic information of the volunteers and data change before and after administration

TABLE-US-00016 Low density lipoprotein cholesterol (mmol/L) Normal group Abnormal group Before After Before After Name Age Gender administration administration Name Age Gender administration administration WXF 36 Male 2.47 2.32 DYF 55 Female 2.88 2.76 WQL 61 Female 2.72 1.98 NJY 48 Male 3.48 1.96 WX 46 Male 2.57 2.04 ZGC 53 Male 2.88 2.74 ZGC 53 Male 2.88 2.74 ZHY 57 Female 3.24 2.05 ZTH 20 Male 2.36 1.74 YHQ 46 Male 3.94 3.57 ZYZ 40 Male 1.72 2.07 JZX 71 Female 3.57 1.59 XDZ 25 Male 2.55 2.08 CJY 44 Male 3.32 2.90 HCL 62 Male 1.83 1.82 WNL 62 Male 4.26 3.61 XJF 58 Female 1.65 2.17 LFG 73 Female 3.59 3.48 CXF 47 Male 2.09 2.13 ZHX 41 Male 3.65 3.66 LMS 57 Male 2.31 1.6 YWJ 67 Male 3.29 2.77 CLZ 38 Female 2.33 1.85 WHZ 53 Female 3.70 3.91 XMJ 57 Female 4.53 3.57 ZZM 51 Male 3.22 3.35 SJF 46 Male 3.10 2.91 LZZ 58 Male 4.32 3.18 WXY 41 Male 5.60 6.11 ZBK 22 Male 2.99 2.62

[0203] FIG. 39b shows the effect of the composition on the low density lipoprotein cholesterol. Y-coordinate represents the concentration of serum low density lipoprotein cholesterol. The left figure shows the effect of the composition on the abnormal group. The composition may obviously decrease the concentration of the serum low density lipoprotein cholesterol, and there is a significant statistic difference (p=0.005). The right figure shows the effect of the composition on normal group. The composition also has a decrease trend on the serum low density lipoprotein cholesterol in the normal group (p=0.064).

[0204] The above result indicates that the composition has a good effect of decreasing the low density lipoprotein cholesterol. Low density lipoprotein binds to cholesterol to transport cholesterol into peripheral tissue cells. Too much low density lipoprotein in blood will form residual particles to be accumulated within the blood vessel wall under blood vessel endothelium. This is the critical first step in the formation of coronary atherosclerosis, which breaks the integrity of endothelial barrier, activates proinflammatory cytokines and chemokines, promotes the generation of reactive oxygen (ROS) (Weber, C. et al. Nat. Med. 2011), finally leading to serious diseases endangering life, such as, angina pectoris, heart stroke and cerebral stroke. Therefore, low density lipoprotein cholesterol is generally called harmful cholesterol. The composition of the present invention may significantly decrease the excessive low density lipoprotein cholesterol, and is of important meaning in preventing the occurrence of cardiovascular and cerebrovascular diseases, and their progress.

[0205] FIG. 39c shows the effect of the composition of the present invention on the high density lipoprotein cholesterol. The composition has no impact on the volunteer with a normal level of high density lipoprotein cholesterol. However, even though there is no statistical significance, a part of patients with low level of high density lipoprotein cholesterol are improved greatly.

[0206] Currently, the common clinical antilipemic agents mainly include HMG-CoA reductase inhibitors (statins drugs), cation exchange resin preparations, and cholesterol transferase inhibitors of small intestines. These therapeutics not only have the side effects of dissolving striated muscle, impairment of liver and renal functions, but also will affect the physiological functions of cholesterol with excessive amount. The composition consists of medicine-food homologous food, and has a very small possibility of side effect, and may obviously decrease the low density lipoprotein cholesterol (harmful cholesterol), specifically improve hypercholesteremia, free of affecting the physiological level of cholesterol and thus, is of great clinical significance.

[0207] <Effect on Triglyceride>

[0208] Triglyceride was tested in this present invention. Table for basic information of the 30 volunteers (9 in the normal group and 21 in the abnormal group) and data change before and after administration

TABLE-US-00017 Triglyceride (mmol/L) Normal group Abnormal group Before After Before After Name Age Gender administration administration Name Age Gender administration administration XDZ 25 Male 1.66 1.56 WXF 36 Male 1.82 1.56 ZHY 57 Female 1.20 0.85 DYF 55 Female 2.44 0.87 HCL 62 Male 0.98 0.95 LWY 58 Female 2.18 1.33 YWJ 67 Male 1.18 1.40 NJY 48 Male 2.25 1.35 XJF 58 Female 1.39 1.21 WQL 61 Female 1.82 2.06 WHZ 53 Female 1.58 1.76 WX 46 Male 3.28 2.43 LZZ 58 Male 1.02 1.60 ZGC 53 Male 2.10 2.39 LMS 57 Male 0.96 0.76 ZTH 20 Male 2.07 1.77 CLZ 38 Female 1.18 1.02 ZYZ 40 Male 8.94 4.21 YHQ 46 Male 3.63 1.43 JZX 71 Female 3.06 3.36 CJY 44 Male 3.07 1.78 WNL 62 Male 1.85 1.45 LFG 73 Female 1.72 1.61 ZHX 41 Male 2.56 2.42 CXF 47 Male 2.91 1.30 XMJ 57 Female 2.45 3.41 ZZM 51 Male 3.10 2.11 SJF 46 Male 1.74 1.45 ZBK 22 Male 2.33 1.46 WXY 41 Male 3.80 1.14

[0209] FIG. 40 shows the effect of the composition on triglyceride. Y-coordinate represents the concentration of serum triglyceride. The left figure shows the effect of the composition on the abnormal serum triglyceride group. The composition may obviously decrease the concentration of the abnormally elevated serum triglyceride, and there are significant statistic differences (p=0.0044). The right figure shows no obvious effect of the composition on the normal serum triglyceride group. The abnormal elevation of the triglyceride level is an independent risk factor to the atherosclerosis and cardiovascular and cerebrovascular diseases (Sandesara P. B., Endocr. Rev. 2019). However, the physiological level of triglyceride plays a crucial role in the aspect of energy metabolism. The composition may selectively decrease the abnormally elevated concentration of triglyceride, but is free of affecting the normal physiological level, may effectively prevent or control the occurrence and progress of ischemic heart diseases, myocardial infarction, heart failure, cerebral stroke and the like.

[0210] <Improvement Effect on Fasting Blood-Glucose>

[0211] Test Method

[0212] Prediabetes volunteers or volunteers in the early stage of diabetes (fasting blood-glucose (FBG)>5.56 to <7.5 mmol/L) were selected as an abnormal FBG group and volunteers with FBG≤5.56 mmol/L were selected as a normal group based on the standards of American Diabetes Association (ADA). The volunteers received blood examination before administration and with 30-day dosing. The volunteers were forbidden to take any food except drinking water after 21:00 the previous night of the examination. The FBG was determined by a glucose oxidase-peroxidase coupling method in a hospital laboratory. Table for basic information of the 32 volunteers (13 in the normal group and 19 in the abnormal group) and changes of the FBG values before and after administration

TABLE-US-00018 FBG (mmol/L) Normal group Abnormal group Before After Before After Name Age Gender administration administration Name Age Gender administration administration DYF 55 Female 5.06 5.10 WXF 36 Male 5.65 5.55 ZTH 20 Male 4.92 4.77 LWY 58 Female 7.40 5.53 XDZ 25 Male 4.70 4.69 NJY 48 Male 5.63 4.78 ZHY 57 Female 5.15 5.35 WQL 61 Female 5.68 5.41 JZX 71 Female 5.42 5.17 WX 46 Male 6.10 5.30 SJB 56 Male 5.20 5.28 ZGC 53 Male 5.76 6.53 CXF 47 Male 3.94 5.10 ZYZ 40 Male 5.59 5.54 ZZM 51 Male 5.23 5.03 YHQ 46 Male 5.90 4.84 ZBK 22 Male 5.11 4.16 WNL 62 Male 5.81 5.49 WXY 41 Male 4.68 5.20 ZHX 41 Male 5.96 5.65 CYJ 44 Male 5.52 5.60 HCL 62 Male 6.06 6.03 XJF 58 Female 5.41 6.05 YWJ 67 Male 7.20 5.62 SDLF 46 Male 5.17 5.11 XHJ 57 Female 5.91 6.07 LZZ 58 Male 5.59 5.93 LMS 57 Male 5.99 5.56 XGY 74 Male 5.99 5.19 LNL 74 Male 6.91 6.14 WQF 60 Male 6.85 5.76 LJH 47 Male 6.36 6.26

[0213] FIG. 41 shows the effect of the composition on FBG. Y-coordinate represents the blood glucose concentration. The left figure shows that the composition may obviously decrease the concentration of the blood glucose for the abnormal blood glucose group, and there are significant statistic differences (p=0.0048). The right figure shows no obvious effect of the composition on the normal blood glucose group.

[0214] The present invention further utilizes glucose tolerance tests to observe the improvement effect of the composition on the insulin resistance of the 8 prediabetes or diabetes volunteers. The volunteers received blood examination before administration and with 14- and 30-day dosing. The volunteers were forbidden to take any food except drinking water after 21:00 the previous night of the examination. In the next morning, venous blood was respectively drawn at 0 min (before taking glucose), 30 min, 1 h and 2 h later after orally taking 75 g glucose solution, thus determining the blood glucose level. FIG. 42 (left) shows the effect on the glucose tolerance test with 14- and 30-day dosing. It can be seen from the figure that the composition has an inhibitory effect on the blood glucose elevation after orally taking the glucose solution, and the inhibitory effect is more obvious with 30-day dosing, indicating the long-term therapeutic effect of the composition. FIG. 42 (right) shows statistical analysis at two time points of 30 min and 1 h of the glucose tolerance test. There are significant statistic differences to the two time points of 30 min (p=0.044) and 1 h (p=0.019) with 30-day dosing. The result indicates that the composition of the present invention may improve the insulin resistance and enhance the sensibility of the body tissue cells to insulin. Insulin resistance always appears before the attack of diabetes firstly. To improve the sensibility of tissues and organs to insulin may prevent the occurrence of diabetes. After the attack of diabetes, because there is only symptomatic treatment, diabetes patients not only need to take medicine during the lifetime, but also ultimately suffer serious complications such as, cardiovascular and cerebrovascular diseases, chronic impairment of renal function, and nerve injury of nerve endings. The composition has an improvement effect on insulin resistance and may prevent the attack and progress of diabetes.

[0215] <Improvement Effect on High Uric Acid in Serum>

[0216] Test Method

[0217] Volunteers with serum uric acid ≥420 mol/L (male) and ≥360 mol/L (female) served as an abnormal serum uric acid group, and volunteers with serum uric acid lower than the level served as a normal serum uric acid group (Liu A D et al, J Atheroscler. Theromb. 2013). The table below shows the basic information of the 28 volunteers (15 in the normal serum uric acid group and 13 in the abnormal serum uric acid group) and changes of the serum uric acid values before and after administration. The volunteers received blood examination before administration and with 30-day dosing. The volunteers were forbidden to take any food except drinking water after 21:00 the previous night of the examination. Serum uric acid was determined by coupled-enzyme assay.

TABLE-US-00019 Uric acid (umol/L) Normal group Abnormal group Before After Before After Name Age Gender administration administration Name Age Gender administration administration DYF 55 Female 359 316 WQL 61 Female 380 353 WX 46 Male 363 387 ZGC 53 Male 520 498 ZHY 57 Female 251 249 ZTH 20 Male 584 533 YHQ 46 Male 261 310 ZYZ 40 Male 456 456 JZX 71 Female 249 211 XDZ 25 Male 673 614 LFG 73 Female 296 286 CJY 44 Male 507 454 CZH 61 Male 319 421 WNL 62 Male 482 517 SJB 56 Male 262 247 ZHX 41 Male 526 469 XMJ 57 Female 318 305 HCL 62 Male 430 399 SJF 46 Male 345 352 YWJ 67 Male 515 476 LZZ 58 Male 378 333 XJF 58 Female 424 375 LMS 57 Male 390 390 ZZM 51 Male 449 373 WXY 41 Male 352 369 ZBK 22 Male 519 496 BJL 41 Male 352 332 WSM 61 Male 402 401

[0218] FIG. 43 shows the effect of the composition on serum uric acid. Y-coordinate represents the concentration of serum uric acid. The right figure shows that the composition may obviously decrease the concentration of the blood glucose for the abnormal serum uric acid group, and there are significant statistic differences (p=0.001). The left figure shows no obvious effect of the composition on the normal serum uric acid group.

[0219] Traditionally, the diseases associated with high-level serum uric acid mainly include symptomatic high-uric acid diseases caused by uric acid crystal, such as gout, acute and chronic arthritis, uric acid-derived kidney stones, acute or chronic renal damage, and the like. In recent years, lots of epidemiological, clinical and experimental studies have indicated that the asymptomatic high-uric acid patients among the crowd have a higher proportion, and the asymptomatic high-uric acid is associated with the pathogenesis of cardiovascular and cerebrovascular diseases, central nervous disorders, diseases of immune and renal systems, erectile dysfunction of disordered sex activity, and sexual apathy and other multiple systemic diseases. The extent of harm on human health caused by these effects of soluble high uric acid is much larger than gout; therefore, high uric acid has been highly concerned in medical and science fields. Hyperuricemia has huge potential risk to human body, but uric acid is an important physiological activator and is of great significance to human health. Uric acid is a kind of powerful ROS antioxidant and peroxynitrite scavenger. Uric acid can scavenge free radicals and chelate metal ions (Frei B, et al., PNAS 1988; Glantzounis G K, et al. Curr Pharm Des 2005; Sautin Y Y, Johnson R J. Nucleosides Nucleotides Nucl Acids 2008). Half of plasma oxidation resistance of human body is from uric acid, and such kind of function is stronger than that of folic acid (Yeum K J, et al., 2004). The physiological level of uric acid may play a protective effect on the integrity of blood vessel endothelium, and is also an important medium to human type-II immunoreaction and plays a crucial role in response to the protective antibody of vaccines (Kool M, et al. J Exp Med 2008; Kool M, et al. Immunity 2011).

[0220] The composition may not affect the normal physiological level of uric acid while controlling hyperuricemia, and is of great significance in maintaining the physiological level of uric acid, and preventing or treating diseases associated with high uric acid.

[0221] <Improvement Effect on Renal Functions>

[0222] Test Method

[0223] Serum creatinine and glomerular filtration rate are the basic methods to determine liver functions. The present invention utilized the detection of serum creatinine level and estimated glomerular filtration rate to prove the improvement effect of the composition on renal functions. The volunteers received blood examination before administration and with 30-day dosing. The volunteers were forbidden to take any food except drinking water after 21:00 the previous night of the examination. In the next morning, venous blood was drawn to conventionally determine the serum creatinine level by a creatinine enzyme method. The table below shows the basic information of the 23 volunteers and changes of the serum creatinine level before and after administration.

TABLE-US-00020 Creatinine (□mol/L) Name Age Gender Before administration After administration WQL 61 Female 47 53 DYF 55 Female 50 54 XMJ 57 Female 53 58 LFG 73 Female 60 55 YHQ 46 Male 62 59 JZX 71 Female 62 61 BJL 41 Male 62 65 CZH 61 Male 64 70 YWJ 67 Male 66 54 ZHY 57 Female 67 65 ZTH 20 Male 74 67 SJB 56 Male 74 59 WXY 41 Male 74 66 WNL 62 Male 76 75 SJF 46 Male 76 74 HCL 62 Male 79 67 ZBK 22 Male 81 66 ZYZ 40 Male 86 75 CJY 44 Male 87 79 WXF 36 Male 89 82 YZP 51 Male 92 77 ZGC 53 Male 96 89 WSM 61 Male 129 106

[0224] FIG. 44 shows correlation analysis on the serum creatinine level before administration and concentration change of serum creatinine after administration Y-coordinate represents the concentration of serum creatinine. The composition may obviously decrease the serum creatinine, and there are significant statistic differences (p=0.0014). Serum creatinine is one of the best indexes to reflect glomerular filtration function. The decrease of the composition on the concentration of serum creatinine reflects the protective effect of the composition on renal functions. Hyperuricemia, hyperglycemia and dyslipidemia will cause impairment of renal function. The protective effect of the composition on renal functions may be an integrated reaction to improve hyperuricemia, hyperglycemia and dyslipidemia.

[0225] FIG. 45 shows correlation analysis on the change rate of serum creatinine after administration with the serum creatinine level before administration. Y-coordinate represents the change rate of serum creatinine concentration after administration; X-coordinate represents the serum creatinine level before administration; the filled dots in the figure show detection data of each patient; the curve shows a linear trend. The decrease degree of the composition on the serum creatinine level is strongly correlated to the serum creatinine level before administration (Correl R=−0.59367); there are significant statistic differences (p=0.000544). The result indicates that the composition may have a stronger ability to promote creatinine to be discharged from the kidney for the volunteer with a higher creatinine level before administration. Such kind of action form is unique and may be related to the two-way regulation thereof on gut microbiota.

[0226] FIG. 46 shows effects of the composition on a part of volunteers with low serum creatinine level (less than 60 mol/L) before administration. The composition may increase the serum creatinine of these volunteers on the contrary, and there are significant statistic differences (p=0.013). Basic serum creatinine is not only an optimal test index for renal function, but also can reflect the basic metabolism of muscle. Low level of creatinine is mainly reflected in consenescence conditions such as, muscle recession, emaciation and liver function damage. The action may be from the enhancement of the composition, and the two-way regulation on gut microbiota. Such an action characteristic shows the adjustment characteristics of the composition on human physiological functions more.

[0227] Effect on the Estimated Glomerular Filtration Rate (eGFR)

[0228] Estimation Method

[0229] eGFR was calculated by the China's improved approach based on the measured value of the above serum creatinine. Volunteers with eGFR<90 mi/L served as an abnormal glomerular filtration rate group. The table below shows basic information of the volunteers and data change after administration.

TABLE-US-00021 Estimated glomerular filtration rate (eGFR) (ml/min) Normal group Abnormal group Before After After After Name Age Gender administration administration Name Age Gender administration administration DYF 55 Female 105.0 102.3 ZGC 53 Male 77.4 84.9 WQL 61 Female 102.7 98.7 ZHY 57 Female 87.6 90.9 WXF 36 Male 95.6 105.6 JZX 71 Female 87.4 88.0 WXY 41 Male 108.5 122.6 CJY 44 Male 87.9 97.8 ZTH 20 Male 126.2 132.4 LFG 73 Female 87.1 89.0 ZYZ 40 Male 96.9 109.8 SJF 46 Male 89.0 105.2 YHQ 46 Male 113.1 116.2 YZP 51 Male 82.7 105.0 WNL 62 Male 96.4 93.5 WSM 61 Male 51.2 64.9 CZH 61 Male 100.5 96.8 HCL 62 Male 91.5 97.5 YWJ 67 Male 95.1 102.0 SJB 56 Male 98.0 107.0 XMJ 57 Female 101.5 98.8 BJL 41 Male 117.1 114.9 ZBK 22 Male 118.2 130.5

[0230] FIG. 47 shows the change of eGFR after administration. Y-coordinate represents eGFR. The left figure shows the improvement effect of the composition on the abnormal glomerular filtration rate group; and there are significant statistic differences (p=0.010). The right figure shows the effect of the composition on the normal glomerular filtration rate group; and there are also significant statistic differences (p=0.031). eGFR may reflect the renal function level better than serum creatinine, and is the way to measure the renal function level and determine the stage of renal diseases. When eGFR value is 60-89 ml/min, it indicates that kidney has slight hypofunction. The treatment started in such stage is the most promising to improve or control the further hypofunction of renal functions. However, there is no good drug at present. The composition shows a good improvement effect on the patients in this stage. When the eGFR value is 90 or more, even though the production function is in the normal scope, diseases associated with lifestyle such as, hyperglycemia, hyperlipidemia, hypertension and obesity are potential risk factors to the impairment of renal function once attack. The composition may relieve the risk of the impairment of renal function to such kind of patients.

[0231] <Improvement Effect on Liver Functions>

[0232] Test Method

[0233] Hepatocellular damage index threshold values obtained by the studies on non-alcoholic fatty liver diseases were used in this present invention (Bedogni G et al. Hepatology 2005). Volunteers with alanine aminotransferase or aspartate aminotransferase >30 U/L served as objects to observe the changes before administration and with 30-day dosing. The volunteers were forbidden to take any food except drinking water after 21:00 the previous night of the examination. In the next morning, venous blood was drawn to determine the activity of alanine aminotransferase or aspartate aminotransferase by a velocity method. The table below shows the basic information of the 10 volunteers and activity changes of the alanine aminotransferase or aspartate aminotransferase before and after administration.

TABLE-US-00022 Alanine aminotransferase (U/L) Aspartate aminotransferase (U/L) Before After Before After Name Age Gender administration administration administration administration ZTH 20 Male 35 30 24 23 ZYZ 40 Male 65 27 30 17 XDZ 25 Male 59 53 35 32 YHQ 46 Male 30 16 53 17 JZX 71 Female 32 29 34 31 HCL 62 Male 46 59 31 34 XJF 58 Female 66 28 64 37 SJB 56 Male 32 31 24 24 CXF 47 Male 44 21 30 22 JJ 56 Female 42 19 30 22

[0234] FIG. 48 (left) shows the improvement effect of the composition on alanine transaminase; FIG. 48 (right) shows the improvement effect of the composition on aspartate aminotransferase (Y-coordinate represents a liver function unit). The composition has significant improvement effects (p=0.027, p=0.039) statistically to alanine transaminase and aspartate aminotransferase to prove that the composition has a protective effect on hepatic cells in the risk state of damage. The elevation of blood glucose and abnormal blood lipid will affect the functions of multiple organs. Liver, as an important viscera of the general metabolic function, usually suffers dysfunction in case of hyperglycemia or abnormal blood lipid. The protective effect of the composition on liver functions may be partially from the decrease of blood glucose and blood lipid.