Application of bifidobacterium longum subsp. Longum and product thereof in aspects of reducing blood sugar, producing acid and improving fatty liver and hyperlipidemia

Abstract

The invention discloses application of bifidobacterium longum subsp. Longum dipro-600 and a product thereof in the aspects of efficiently reducing blood sugar, producing short-chain fatty acid and improving non-alcoholic fatty liver disease and hyperlipidemia. The dipro-600 disclosed by the invention can be used for remarkably reducing the contents of total cholesterol, low-density lipoprotein, lipopolysaccharide and glutamic oxalacetic transaminase in blood of a mouse with hyperlipidemia; the liver lipid accumulation caused by the non-alcoholic fatty liver is improved. Therefore, the bifidobacterium longum subsp. Longum dipro-600 strain has a good commercial prospect when being used for preparing products for reducing blood sugar, producing short-chain fatty acid, reducing cholesterol and improving non-alcoholic fatty liver and hyperlipidemia.

Description

Technical Field

[0001] The present invention belongs to the field of microbial technology and relates to the application of Bifidobacterium longum subsp. longum and its products in lowering blood sugar, producing acid, improving fatty liver and hyperlipidemia, and specifically relates to the application of Bifidobacterium longum subsp. longum in efficiently lowering blood sugar, producing lactic acid and short-chain fatty acids, and improving non-alcoholic fatty liver and hyperlipidemia through the gut-liver axis. Background Art

[0002] With changes in modern dietary patterns and the prevalence of industrial sugars (particularly fructose syrup), the incidence of non-alcoholic fatty liver disease (NAFLD) and hyperlipidemia has steadily increased, becoming a major threat to global public health. Recent studies have found that excessive fructose intake can easily lead to dysbiosis, intestinal barrier damage, and endotoxemia, further promoting systemic inflammation and metabolic disorders. Fructose promotes hepatic lipogenesis by activating the ChREBP transcription factor, which is directly related to non-alcoholic fatty liver disease (NAFLD). Current clinical treatments have limitations. Traditional medications (such as statins and fibrates) may cause side effects such as liver and kidney dysfunction. While traditional Chinese medicine formulas have some efficacy, they are complex in composition and have unclear mechanisms of action. In recent years, probiotics have become a research hotspot for metabolic disease intervention due to their inherent safety and multi-target regulation.

[0003] Studies have shown that Bifidobacterium longum subspecies longum can alleviate metabolic syndrome by regulating intestinal flora and improving lipid metabolism disorders. For example, the strain dipro-O, also from the genus Bifidobacterium longum, lowers cholesterol and reduces liver fat accumulation by enhancing bile salt hydrolase activity; while other strains, such as CCFM1319, improve constipation by repairing intestinal barrier function.

[0004] However, existing strains still have functional limitations in regulating sugar metabolism, producing short-chain fatty acids, and targeting the gut-liver axis, and there is an urgent need to develop strains with more comprehensive metabolic regulation capabilities. Summary of the Invention

[0005] Purpose of the invention: The technical problem to be solved by the present invention is to provide a strain of Bifidobacterium longum subsp. longum dipro-600 that can simultaneously and efficiently lower blood sugar and produce acid and improve non-alcoholic fatty liver disease and hyperlipidemia through the gut-liver axis.

[0006] The technical problem that the present invention also aims to solve is to provide a product containing the Bifidobacterium longum subsp. longum dipro-600.

[0007] The technical problem that the present invention also aims to solve is the use of the Bifidobacterium longum subsp. longum dipro-600 or the product in the preparation of products for lowering blood sugar, producing acid, lowering cholesterol, and improving non-alcoholic fatty liver disease and / or hyperlipidemia.

[0008] Technical solution: In order to solve the above technical problems, the Bifidobacterium longum subsp. longum dipro-600 described in the present invention was deposited in the General Microbiology Center of the China Culture Collection Administration on January 10, 2024, with the deposit number: CGMCC No. 29571, and the deposit address is: Beijing, China.

[0009] The Bifidobacterium longum subsp. longum dipro-600 of the present invention is a Bifidobacterium longum subsp. longum isolated from the feces of healthy children. Whole genome sequencing analysis and comparison of the strain show that the strain is Bifidobacterium longum subsp. longum.

[0010] The Bifidobacterium longum subsp. longum dipro-600 can efficiently utilize sugars, including but not limited to monosaccharides, disaccharides and polysaccharides, with a sugar utilization rate of 20% to 100%.

[0011] The strain can directly metabolize and produce lactic acid and short-chain fatty acids. Preferably, the types of short-chain fatty acids are mainly formic acid, acetic acid, and propionic acid.

[0012] The strain can directly reduce the cholesterol level in the culture medium, and the cholesterol reduction ratio is 10% to 100%.

[0013] The present invention also includes products containing the Bifidobacterium longum subsp. longum dipro-600, including fermented products, foods, health products, medicines or feeds.

[0014] Wherein, the fermentation product comprises a fermentation culture of Bifidobacterium longum subsp. longum dipro-600. Preferably, the fermentation culture comprises a fermentation supernatant or a fermentation precipitate or a combination thereof; preferably, the fermentation product also comprises a fermentation lysate, a fermentation extract, an inactivated product or a combination thereof.

[0015] The dosage forms of the product include powder, capsule, tablet, pill, film-coated agent, aerosol, granule, liquid, liposome, transdermal agent, suppository or lyophilized powder injection.

[0016] The product further comprises at least one of a protective agent, a functional aid, an auxiliary additive and a drug carrier. Preferably, the auxiliary additive comprises a pharmaceutical excipient.

[0017] Among them, the protective agent, functional aid, auxiliary additive, drug carrier or pharmaceutical excipient includes but is not limited to albumin, gelatin, soluble starch, dextrin, meat juice, pectin, gum arabic, hydroxymethyl cellulose, algae, vitamin D, vitamin E, protein hydrolyzate, sodium thiosulfate, dextran and natural mixtures such as skim milk, serum, etc.

[0018] The present invention also includes the use of the Bifidobacterium longum subsp. longum dipro-600 product in the preparation of products for lowering blood sugar, producing acid, lowering cholesterol, and improving non-alcoholic fatty liver disease and / or hyperlipidemia.

[0019] The present invention also includes the use of the Bifidobacterium longum subsp. longum dipro-60 in the product having at least one of the following functions:

[0020] 1) Products that can efficiently utilize sugars;

[0021] 2) products that can be metabolized to produce acid;

[0022] 3) Products that can lower cholesterol;

[0023] 4) Products that can improve non-alcoholic fatty liver disease;

[0024] 5) Products that can improve hyperlipidemia;

[0025] The present invention also includes the product capable of efficiently utilizing sugars, wherein the sugars include monosaccharides, disaccharides, or polysaccharides. Preferably, the product capable of efficiently utilizing sugars is a product that utilizes Bifidobacterium longum subsp. longum dipro-600 to metabolize and utilize fructose and mannose for rapid growth and to efficiently reduce the content of fructose and mannose.

[0026] Preferably, the product capable of metabolizing to produce acid is a product that can metabolize to produce lactic acid, formic acid, acetic acid and propionic acid or a combination thereof using Bifidobacterium longum subsp. longum dipro-600;

[0027] Preferably, the product capable of lowering cholesterol is a product that can directly lower cholesterol in the culture medium.

[0028] The present invention also includes the product for improving non-alcoholic fatty liver disease, specifically a product that uses Bifidobacterium longum subsp. longum dipro-600 to improve liver lipid accumulation caused by non-alcoholic fatty liver disease;

[0029] Preferably, the product capable of improving hyperlipidemia is a product that uses Bifidobacterium longum subsp. longum dipro-600 to reduce the total cholesterol content, low-density lipoprotein content, lipopolysaccharide (LPS) content and aspartate aminotransferase (AST) content in hyperlipidemia.

[0030] In summary, the present invention reports for the first time that the intake of Bifidobacterium longum subsp. longum dipro-600 can simultaneously and efficiently lower blood sugar, produce lactic acid and short-chain fatty acids, and improve non-alcoholic fatty liver disease and hyperlipidemia through the gut-liver axis.

[0031] Beneficial effects: Compared with the existing technology, the long bifidobacterium subspecies longum dipro-600 provided by the present invention breaks through the bottleneck of the existing technology, and has the ability to efficiently utilize sugar, produce acid and lower cholesterol; further animal experiments show that dipro-600 can improve non-alcoholic fatty liver disease through the gut-liver axis, wherein dipro-600 can significantly reduce the total cholesterol, low-density lipoprotein, lipopolysaccharide and aspartate aminotransferase levels in the blood of hyperlipidemic mice, and improve the liver lipid accumulation caused by non-alcoholic fatty liver disease. Therefore, the use of the long bifidobacterium subspecies longum dipro-600 strain for the preparation of products that lower blood sugar, produce acid, lower cholesterol, and improve non-alcoholic fatty liver disease and hyperlipidemia has a good prospect, and provides a safer and more efficient microbial intervention program for the prevention and treatment of metabolic syndrome. It is especially suitable for patients with NAFLD and hyperlipidemia who require long-term management, and has broad clinical application prospects. This strain has the following specific advantages: 1. Optimized metabolic function: It efficiently utilizes carbohydrate substrates and metabolizes them to produce lactic acid and short-chain fatty acids, and improves the host's energy metabolism imbalance by regulating the intestinal microenvironment; 2. Enhanced lipid-lowering mechanism: The experimental results of the present invention show that its cholesterol-lowering effect is better than that of traditional strains, reducing lipid absorption; 3. Targeted intervention of the gut-liver axis: In animal models, dipro-600 significantly reduced the serum total cholesterol level of hyperlipidemic mice (by 24.5%), reversed liver lipid accumulation, and improved NAFLD pathological indicators (such as a 29.7% decrease in AST levels). BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 This is the result of the test of the high-efficiency blood sugar-lowering ability of Bifidobacterium longum subspecies longum dipro-600. Figure 1 A is the OD600 value determination of the growth of different bacteria using fructose and mannose; Figure 1 B is the utilization rate of fructose and mannose by different strains.

[0033] Figure 2 This is a graph showing the results of the lactic acid and short-chain fatty acid production capacity test of Bifidobacterium longum subspecies longum dipro-600. Figure 2 A is a peak diagram for determining lactic acid in the culture supernatant of Bifidobacterium longum subsp. longum dipro-600; Figure 2 B is the peak diagram for the determination of short-chain fatty acids in the culture supernatant of Bifidobacterium longum subsp. longum dipro-600; Figure 2 C is the determination of the content of short-chain fatty acids in the culture supernatant of Bifidobacterium longum subsp. longum dipro-600.

[0034] Figure 3 This is a graph showing the cholesterol-lowering ability test results of Bifidobacterium longum subsp. longum dipro-600.

[0035] Figure 4This figure shows the improvement results of Bifidobacterium longum subsp. longum dipro-600 on the non-alcoholic fatty liver disease mouse model.

[0036] Figure 5 This figure shows the improvement results of Bifidobacterium longum subspecies longum dipro-600 on the hyperlipidemia mouse model. Figure 5 A represents the results of the measurement of total cholesterol content in the blood of the hyperlipidemia mouse model; Figure 5 B represents the results of the determination of low-density lipoprotein levels in the blood of hyperlipidemia mouse models; Figure 5 C represents the statistical results of the ratio of total cholesterol content to high-density lipoprotein content in the hyperlipidemia mouse model; Figure 5 D represents the determination of lipopolysaccharide (LPS) content in the blood of hyperlipidemia mouse model; Figure 5 E represents the determination of aspartate aminotransferase (AST) content in the blood of hyperlipidemia mouse model. DETAILED DESCRIPTION

[0037] The present invention will be described in detail below with reference to the accompanying drawings and embodiments.

[0038] Example 1 Microbiological identification of strain dipro-600

[0039] Bifidobacterium longum subsp. longum dipro-600 was isolated from the feces of healthy children and identified by MALDI-TOF, 16SrRNA sequencing and whole genome sequencing. The strain was identified as Bifidobacterium longum subsp. longum. The Bifidobacterium longum subsp. longum dipro-600 of the present invention was deposited in the General Microbiology Center of the China Culture Collection Administration on January 10, 2024, with a deposit address of: Beijing, China, and a deposit number of: CGMCC No. 29571.

[0040] When conducting various experiments, the glycerol cryovial of Bifidobacterium longum subsp. longum dipro-600 was taken out from the -80°C refrigerator, thawed in a 37°C water bath, and 50 μL was spread on an MRS+ (MRS (Guangdong Huankai Microbiology Technology Co., Ltd., product number: 027315) + cysteine with a final concentration of 0.5 g / L) plate, and placed in 37°C anaerobic culture for 48 hours; then, a single clone was picked and streaked with an inoculation loop for subculture. After 48 hours, a single clone colony was picked and transferred to MRS broth liquid culture medium (MRS+) supplemented with cysteine with a final concentration of 0.5 g / L, and incubated in a constant temperature culture at 37°C for 48 hours for expansion culture, and then subsequent experiments could be carried out.

[0041] Example 2 Determination of the Highly Effective Blood Sugar-Lowering Ability of Bifidobacterium longum subspecies longum dipro-600

[0042] Bifidobacterium longum subspecies dipro-600 and reference strain Bifidobacterium longum subspecies infantis M-63 (Morinaga, Japan), Bifidobacterium animalis lactis subspecies BPL1 (ADM, USA), and Bifidobacterium longum subspecies BB536 (Morinaga, Japan) were inoculated into MRS broth liquid culture medium (MRS+) containing 0.5 g / L cysteine and incubated at 37°C for 48 hours for expansion culture. After the culture was completed, the cells were centrifuged at 8000 rpm for 3 minutes, the supernatant was removed, and the cells were washed twice with phosphate buffered saline (PBS) (Procell, 10 mM, pH 7.2-7.4, catalog number: PB180327) and resuspended to OD600 = 1.0. A carbon-free MRS+ liquid culture medium with a final concentration of 1% fructose or 1% mannose was prepared. Add 20 μL of each cultured bacterial suspension to 180 μL of carbon-free MRS+ liquid medium supplemented with 1% fructose or 1% mannose on a 96-well plate, and culture at 37°C for 48 hours. The specific grouping is shown in Table 1:

[0043] Table 1 Grouping of strains treated with different sugars

[0044]

[0045]

[0046] After the culture was completed, the OD600 value was measured to compare the growth of different strains in the same carbon source. The results were as follows: Figure 1 As shown in A, all strains can grow on fructose or mannose, but dipro-600 measured a higher OD600 value, indicating that dipro-600 can utilize these two carbon sources more efficiently, showing good sugar metabolism and growth ability. Bromocresol purple was added as a color indicator at a final concentration of 0.17g / L to further determine its relative sugar utilization rate. The results are shown in Figure 1 As shown in Figure B, dipro-600 has a high utilization rate for both sugars, with a utilization rate of 52.31% for fructose and 51.96% for mannose. In summary, dipro-600 has excellent ability to metabolize fructose and mannose, and can effectively reduce the sugar content in the culture medium.

[0047] Example 3 Determination of Acid Production Capacity of Bifidobacterium longum subspecies longum dipro-600

[0048] According to the strain expansion method in Example 1, Bifidobacterium longum subspecies dipro-600 was inoculated into M9 (Shanghai Huzhen Biotechnology Co., Ltd., Article No.: HZ0060-500mL) culture medium, and cultured anaerobically at 37°C for 48h. The supernatant was extracted by centrifugation at a speed of 8000rpm for 3min, and filtered with a 0.22um filter membrane. The content of lactic acid and short-chain fatty acids (SCFAs) in the supernatant was determined by high performance liquid chromatography (HPLC). The lactic acid peak in the supernatant of Bifidobacterium longum subspecies dipro-600 was measured as follows: Figure 2 As shown in A, its content is 3275.79 mg / L, and the results of short-chain fatty acids are as follows Figure 2 B and 2C, where Figure 2 B is the peak diagram of various short-chain fatty acids in the supernatant, which are formic acid, acetic acid and propionic acid from left to right; Figure 2 C is the measured content of various short-chain fatty acids in the supernatant, of which the formic acid content is 52.57 mg / L, the acetic acid content is 194.93 mg / L, and the propionic acid content is 66.39 mg / L.

[0049] Example 4 Determination of cholesterol-lowering ability of Bifidobacterium longum subspecies longum dipro-600

[0050] Bifidobacterium longum subsp. dipro-600, reference strains Bifidobacterium breve B3 (Morinaga, Japan), and Bifidobacterium animalis subsp. lactis BPL1 (ADM, USA) were inoculated into freshly prepared MRS+ liquid culture medium containing 0.3% (w / v) bile salts and 0.1 g / L cholesterol (soluble in anhydrous ethanol, Sigma-Aldrich) and incubated at 37°C for 24 hours. The supernatant was then centrifuged at 4000 g for 15 minutes at 4°C and the cholesterol content in the supernatant was determined using a cholesterol detection kit (E-BC-K109-M). A blank culture medium without bacteria and cultured in parallel was used as the control group (control group); the measurement results are shown in Figure 2. Figure 3 As shown, the cholesterol-lowering rate of the reference strain B3 was 14.67%, the cholesterol-lowering rate of BPL1 was 13.67%, and the cholesterol-lowering rate of Bifidobacterium longum subsp. longum dipro-600 was 17.98%, indicating that Bifidobacterium longum subsp. longum dipro-600 had a stronger cholesterol-lowering ability.

[0051] Example 5 Bifidobacterium longum subsp. longum dipro-600 has an improving effect on the animal model of non-alcoholic fatty liver disease induced by methionine and choline deficient diet

[0052] Eighteen eight-week-old male C57BL / 6J mice were randomly divided into four groups: a normal diet group (NC group); a model control group (PBS group); and a probiotic group (dipro-600 group). The normal diet group (NC group) maintained a normal diet (synergistic biological irradiation sterilized laboratory mouse growth and breeding diet, Catalog No.: XTI01CR-004). The model group and probiotic-treated group were fed a Dyets methionine- and choline-deficient mouse diet (Dyets, Catalog No.: 519580) for four weeks to establish a non-alcoholic fatty liver disease model. The mouse groups and gavage treatments are shown in Table 2:

[0053] Table 2 Treatment status of different groups

[0054]

[0055] Oral administration: Bifidobacterium longum subsp. longum dipro-600 was fermented anaerobicy at 37°C, and the fermentation broth was centrifuged to obtain a bacterial pellet, which was then resuspended in phosphate buffered saline (PBS) (Procell, 10 mM, pH 7.2-7.4, Cat. No. PB180327). The OD600 was adjusted to 2.5, and the bacterial concentration was 5*10 9 CFU / mL, each mouse was gavaged with 200 μL per day for 4 weeks.

[0056] When the gavage endpoint was reached, the mice were killed and their livers were collected for HE staining. Figure 4 As shown, from Figure 4 It can be seen that compared with the normal group, a large number of vacuoles appeared in the liver tissue of the PBS group, which was caused by lipid accumulation in the liver. At the same time, many inflammatory cells were observed to infiltrate, indicating that it had a more serious inflammation. In comparison, the number of vacuoles in the liver of mice in the dipro-600 treatment group was reduced, and there was also little inflammatory cell infiltration, indicating that dipro-600 can effectively improve the symptoms of non-alcoholic fatty liver disease.

[0057] Example 6 Bifidobacterium longum subspecies longum dipro-600 has an improving effect on the hyperlipidemia mouse model

[0058] Eighteen eight-week-old male C57BL / 6J mice were randomly divided into three groups: a normal control group (NC group), a hyperlipidemia model group (PBS group), and a dipro-600-treated group (dipro-600). The NC group was maintained on a normal diet (Synergy Bio-Irradiated Sterilized Laboratory Mouse Growth and Reproduction Diet, Catalog No. XTI01CR-004), while the PBS and dipro-600 groups were fed a Dyets high-fat (40 kcal%), high-cholesterol (1.25%), and high-sodium cholate (0.5%) mouse diet (Dyets, Catalog No. ASHF4) for six weeks to establish a hyperlipidemia model, followed by oral gavage. Gavage conditions: Bifidobacterium longum subsp. longum dipro-600 was fermented anaerobicy at 37°C, the fermentation broth was centrifuged and resuspended in phosphate buffered saline (PBS) (Procell, 10 mM, pH 7.2-7.4, Cat. No. PB180327), and the OD600 was adjusted to 2.5. The bacterial concentration was 5*10 9 CFU / ml, each mouse was gavaged with 200 μL per day for 6 weeks.

[0059] Blood samples were collected from mice at the end of oral administration, and blood lipid indexes were tested for mice in different treatment groups. Figure 5 As shown in the results, compared with the PBS control group, the oral dipro-600 treatment group was able to significantly reduce the total cholesterol (TC) content, low-density lipoprotein (LDL) level and the ratio of total cholesterol (TC) to high-density lipoprotein (HDL) in the blood of hyperlipidemic mice ( Figure 5 A, 5B, 5C), indicating that dipro-600 has a positive effect on the blood lipids of hyperlipidemia model mice.

[0060] At the same time, the content of lipopolysaccharide (LPS) in the blood was measured. The results were as follows: Figure 5 As shown in D, compared with the PBS group, intervention with Bifidobacterium longum dipro-600 in the ASHF-induced hyperlipidemia mouse model significantly reduced the level of LPS in the blood.

[0061] At the same time, the level of aspartate aminotransferase (AST) in the blood was measured. Figure 5 As shown in Figure E, compared with the PBS group, dipro-600 effectively reduced blood aspartate aminotransferase (AST) levels in the ASHF-induced hyperlipidemia mouse model. AST is a key transaminase and a clinical indicator of liver function, used to assess liver damage. This suggests that dipro-600 intervention alleviated liver damage caused by hyperlipidemia in mice.

[0062] The comprehensive results of the above indicators show that dipro-600 has a good effect in improving hyperlipidemia.

Claims

1. A strain of Bifidobacterium longum subsp. longum dipro-600, characterized in that The Bifidobacterium longum subsp. longum dipro-600 was deposited in the General Microbiology Center of the China Culture Collection Administration on January 10, 2024, with the deposit number: CGMCC No.29571.

2. The Bifidobacterium longum subsp. longum dipro-600 according to claim 1, characterized in that The Bifidobacterium longum subsp. longum dipro-600 can efficiently utilize carbohydrates, and its carbohydrate utilization rate is 20% to 100%; preferably, the Bifidobacterium longum subsp. longum dipro-600 can directly reduce the cholesterol content, and its cholesterol reduction ratio is 10% to 100%; preferably, the Bifidobacterium longum subsp. longum dipro-600 can metabolize to produce lactic acid and short-chain fatty acids, and preferably, the types of the short-chain fatty acids are mainly formic acid, acetic acid and propionic acid.

3. A product containing Bifidobacterium longum subsp. longum dipro-600 according to claim 1, characterized in that The products include fermented products, foods, health products, medicines or feeds.

4. The product according to claim 3, wherein the fermented product comprises a fermentation culture of Bifidobacterium longum subsp. longum dipro-600, preferably, the fermentation culture comprises a fermentation supernatant or a fermentation precipitate or a combination thereof; preferably, the fermented product further comprises a fermentation lysate, a fermentation extract, an inactivated product or a combination thereof.

5. The product according to claim 3, characterized in that The dosage forms of the product include powder, capsule, tablet, pill, film-coated agent, aerosol, granule, liquid, liposome, transdermal agent, suppository or lyophilized powder injection.

6. The product according to claim 3, characterized in that The product further comprises at least one of a protective agent, a functional aid, an auxiliary additive and a drug carrier. Preferably, the auxiliary additive comprises a pharmaceutical excipient.

7. Use of the Bifidobacterium longum subsp. longum dipro-600 according to claim 1 or the product according to any one of claims 2 to 5 in the preparation of a product for lowering blood sugar, acid production, lowering cholesterol, and improving non-alcoholic fatty liver disease and / or hyperlipidemia.

8. The use according to claim 7, characterized in that The application of the product is a product that has at least one of the following functions: 1) Products that can efficiently utilize sugars; 2) products that can be metabolized to produce acid; 3) Products that can lower cholesterol; 4) Products that can improve or treat non-alcoholic fatty liver disease; 5) Products that can improve or treat hyperlipidemia.

9. The use according to claim 8, characterized in that The sugars include monosaccharides, disaccharides or polysaccharides. Preferably, the product capable of efficiently utilizing sugars is a product that utilizes the metabolism of Bifidobacterium longum subsp. longum dipro-600 to rapidly grow by utilizing fructose and mannose and efficiently reduce the content of fructose and mannose. Preferably, the product capable of metabolizing to produce acid is a product that is metabolized by Bifidobacterium longum subsp. longum dipro-600 to produce lactic acid, formic acid, acetic acid, propionic acid or a combination thereof; Preferably, the product capable of lowering cholesterol is a product that directly lowers cholesterol in the culture medium.

10. The use according to claim 8, characterized in that The product capable of improving non-alcoholic fatty liver disease specifically refers to a product that improves liver lipid accumulation caused by non-alcoholic fatty liver disease; Preferably, the product capable of improving hyperlipidemia is a product that uses Bifidobacterium longum subsp. longum dipro-600 to reduce the total cholesterol content, low-density lipoprotein content, lipopolysaccharide content and / or aspartate aminotransferase content in hyperlipidemia.

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