Healthy human-derived intestinal fungus Yarrowia lipolytica PT3309 and application thereof

Abstract

The invention discloses an intestinal fungus Yarrowia lipolytica (Yarrowia lipolytica) PT3309 derived from healthy people and application of the intestinal fungus Yarrowia lipolytica PT3309, and belongs to the field of functional microorganisms. The strain preservation number of the yarrowia lipolytica PT3309 is GDMCC (Grains Database Microorganism Center) 65342. The yarrowia lipolytica PT3309 can tolerate the gastrointestinal environment of a human body, and can be efficiently adhered to an intestinal epithelial cell Caco2. The yarrowia lipolytica PT3309 and biomass energy thereof can relieve weight loss, hematochezia and diarrhea of inflammatory bowel disease model mice, improve colon pathological changes, reduce expression of inflammatory factors such as IL-1beta, IL-6 and TNF-alpha, and restore colon epithelial barriers. The Yarrowia lipolytica PT3309 provided by the invention can be used for preparing functional microbial agents, foods and medicines for relieving inflammatory bowel diseases, and has a wide application prospect.

Description

Technical Field

[0001] The present invention relates to a healthy human-derived intestinal fungus Yarrowia lipolytica PT3309 and application thereof in preventing and treating inflammatory bowel disease, belonging to the technical field of functional microorganisms. Background Art

[0002] Inflammatory bowel disease (IBD) is a chronic, nonspecific intestinal inflammatory disease characterized by recurrent diarrhea, bloody and mucus-purulent stools, abdominal pain, and tenesmus, severely impacting patients' quality of life. IBD, which can be divided into ulcerative colitis (UC) and Crohn's disease (CD), has been dubbed a "green cancer" due to its recurring and persistent nature. Currently, emerging industrialized countries such as my country are experiencing an accelerated incidence of IBD, with the incidence expected to rise rapidly over the next decade. With an aging population and declining fertility rates, my country's public health resources will face significant challenges in addressing the IBD epidemic. Currently, conventional treatments for IBD include aminosalicylic acid preparations, immunosuppressants such as glucocorticoids, and biologics such as infliximab. However, these treatments often only provide temporary relief from IBD symptoms and are often associated with adverse reactions such as drug resistance, hormone dependence, and immunosuppression, leading to reduced patient compliance and a vicious cycle of relapse-remission-relapse. Therefore, developing long-acting and safe IBD treatment drugs to improve the quality of life and health level of my country's large IBD population is a long-term and urgent challenge facing medical researchers.

[0003] Intestinal microorganisms are important participants in the occurrence and development of IBD, and changes in the intestinal flora are key clinical events in the pathological process of IBD. Changes in the abundance and diversity of intestinal flora directly drive the intestinal immune response and continuously induce chronic inflammation. At the same time, the use of probiotics to reshape the intestinal flora has made fecal microbiome transplantation (FMT) an important strategy for the prevention and treatment of IBD. Current research on the impact of intestinal flora on disease progression often focuses on intestinal bacteria; however, intestinal fungi, as an important intestinal flora, play a key role in the occurrence and development of the disease, but are often ignored due to technical limitations and insufficient cognition. Yarrowia lipolytica PT3309 is an intestinal functional fungus obtained by systematically analyzing the intestinal fungal community of healthy people through large-scale culture omics technology. Its biological functions, especially its effects on IBD, have not been reported. Therefore, the present invention comprehensively uses microbial and pharmacological experimental techniques to discover probiotic resources that can be used to prevent and treat IBD from human intestinal fungi. Summary of the Invention

[0004] In view of the above problems, the present invention aims to provide a functional intestinal fungus for preventing and treating inflammatory bowel disease.

[0005] In a first aspect, the present invention provides a strain of Yarrowia lipolytica ( Yarrowia lipolytica ) PT3309, which was deposited with the Guangdong Provincial Center for Microbiological Culture Collection under the accession number GDMCC 65342 and the date of deposit on October 24, 2024. This strain was isolated from a healthy human fecal sample and is characterized by tolerance to gastric acid and intestinal fluid and high intestinal adhesion.

[0006] In a second aspect, the Yarrowia lipolytica PT3309 is used to prepare a product for preventing or treating inflammatory bowel disease (IBD), regulating the balance of intestinal flora, having antioxidant activity and repairing the intestinal barrier.

[0007] Furthermore, the inflammatory bowel disease is ulcerative colitis or Crohn's disease.

[0008] Furthermore, the therapeutic effects of the product include at least one of the following:

[0009] 1. Reduce weight loss, bloody stools and diarrhea symptoms;

[0010] 2. Improve colon mucosal damage and pathological changes;

[0011] 3. Reduce the expression of inflammatory factors IL-1β, IL-6, and TNF-α in the colon;

[0012] 4. Upregulate the expression of tight junction proteins Claudin-1 and ZO-1 to repair intestinal epithelial barrier function.

[0013] Thirdly, the forms of the products include:

[0014] 1. Probiotic preparations: composed of live bacteria, freeze-dried bacterial powder, heat-inactivated bacterial biomass, or strain metabolites of Yarrowia lipolytica PT3309;

[0015] 2. Drugs or pharmaceutical compositions: viable bacteria, lyophilized bacterial powder, heat-inactivated bacterial biomass, or strain metabolites of Yarrowia lipolytica PT3309 and a pharmaceutically acceptable carrier (e.g., milk powder, lactose, cyclodextrin, maltose, glucose, glycerol, monosodium glutamate, vitamin C, mannose, galactose, mannan, or methylcellulose). Dosage forms include oral preparations, suppositories, or injections.

[0016] 3. Fermented foods: Produced by fermentation with Yarrowia lipolytica PT3309, including solid foods, liquid foods, semi-solid foods, dairy products, fruit and vegetable foods, and freeze-dried foods.

[0017] 4. A functional food comprising live bacteria, freeze-dried bacterial powder, heat-inactivated bacterial biomass, or strain metabolites of Yarrowia lipolytica PT3309, the functional food being prepared by a fermentation process or by directly adding bacterial cells, and being selected from fermented dairy products, fermented fruit and vegetable juices, biscuits, beverages, or nutritional supplements.

[0018] In a fourth aspect, the Yarrowia lipolytica PT3309 achieves the prevention and treatment of inflammatory bowel disease through the following mechanisms:

[0019] 1. Regulate the balance of intestinal flora, specifically increase the abundance of beneficial bacteria such as Lactobacillus and inhibit the proliferation of harmful bacteria such as Enterobacteriaceae;

[0020] 2. Antioxidant effect: reduces intestinal oxidative stress levels;

[0021] 3. Immune regulation: inhibit the release of pro-inflammatory factors and restore immune homeostasis.

[0022] 4. Repair intestinal epithelial barrier function: Upregulate the expression of tight junction proteins such as Claudin-1 and ZO-1 to restore intestinal epithelial barrier function.

[0023] Technical Results: Animal experiments have shown that Yarrowia lipolytica PT3309 significantly alleviates IBD symptoms in mice, improves colon length shortening and tissue pathological damage, reduces inflammatory cytokine levels, and achieves long-term protection by repairing intestinal epithelial barrier function. This strain has potential for application in the development of functional foods, probiotic preparations, and pharmaceuticals.

[0024] The present invention isolated and identified a strain of intestinal fungus, Yarrowia lipolytica PT3309, from healthy human fecal samples. The strain exhibits tolerance to gastric acid and intestinal fluid and exhibits high intestinal adhesion. This strain significantly alleviated inflammatory bowel disease (IBD) symptoms in mice, alleviated colonic pathological changes, inhibited the expression of colonic IL-1β, IL-6, and TNF-α, upregulated the expression of tight junction proteins such as Claudin-1 and ZO-1, and restored intestinal epithelial barrier function, suggesting broad application prospects in the prevention and treatment of IBD. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0026] Figure 1 is a scanning electron micrograph of Yarrowia lipolytica PT3309;

[0027] Figure 2 is the growth curve of Yarrowia lipolytica PT3309;

[0028] Figure 3 This figure shows the therapeutic effect of live Yarrowia lipolytica PT3309 bacteria and heat-killed bacterial biomass on the inflammatory bowel disease phenotype in wild-type mice compared with the model group in Example 3, where A represents the weight change of mice; B represents the diarrhea score of mice; and C represents the bloody stool of mice.

[0029] Figure 4 3. The effect of Yarrowia lipolytica PT3309 on colonic permeability in wild-type inflammatory bowel disease mice in Example 3; wherein A is a fluorescence image of FITC-dextran in plasma, and B is a fluorescence quantification image of FITC-dextran in plasma;

[0030] Figure 5 The results of the effect of Yarrowia lipolytica PT3309 on colonic lesions in mice with inflammatory bowel disease in Example 3; wherein A is a colonoscopy image, and B is a HE-stained section of colon tissue;

[0031] Figure 6 The effect of Yarrowia lipolytica PT3309 on the colon length of mice with inflammatory bowel disease in Example 3; wherein A is a colon photo and B is the statistical data of colon length;

[0032] Figure 7 The expression of inflammatory factors IL-1β, IL-6, and TNF-α in the colon tissue of mice after colonization with Yarrowia lipolytica PT3309 in Example 3;

[0033] Figure 8 The weight, diarrhea score, and bloody stool of mice subjected to antibiotic-depleted intestinal flora (ABX) treatment with Yarrowia lipolytica PT3309 in Example 4 are shown, where A represents the weight change of mice; B represents the bloody stool of mice; and C represents the diarrhea score of mice.

[0034] Figure 9 4 shows the effect of Yarrowia lipolytica PT3309 on colonic permeability in ABX inflammatory bowel disease mice; wherein A is a fluorescence image of FITC-dextran in plasma, and B is a fluorescence quantification image of FITC-dextran in plasma;

[0035] Figure 10 The results of the effect of Yarrowia lipolytica PT3309 on colonic lesions in ABX inflammatory bowel disease mice in Example 4 are shown; wherein A is a colonoscopic image, and B is a HE-stained section of colon tissue;

[0036] Figure 11The colon length results of ABX mice after Yarrowia lipolytica PT3309 colonization in Example 4, where A is a colon photo, B is the colon length statistics; C is the expression of inflammatory factors IL-1β, IL-6, and TNF-α in colon tissue. DETAILED DESCRIPTION

[0037] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0038] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the present invention is further described in detail below with reference to the accompanying drawings and specific embodiments.

[0039] Example 1 Strain Isolation and Identification

[0040] Fresh human fecal samples were diluted with sterile water, spread onto MTB culture medium (penicillin 100 U / mL, streptomycin 100 μg / mL), and cultured in a 32°C incubator for 5-10 days. When distinct colonies were observed, colonies with different morphologies were picked and plated on new MTB culture plates. Culture was continued in a 32°C incubator for 3 days. Once monoclonal colonies were observed, monoclonal strains were further cultured to obtain purified monoclonal intestinal fungi. The strain of the present invention was a white, round colony with a smooth surface (number PT3309). The bacterial solution was placed in a 50% glycerol aqueous solution and stored at -80°C. At the same time, the nucleic acid of the isolated strain was extracted using a DNA extraction kit, and RT-PCR was performed using 18S rDNA primers. Combined with sequencing technology, the 18S rRNA gene of the isolated strain was sequenced and analyzed. Combined with BLAST comparison of the nucleic acid database of the National Center for Biotechnology Information (NCBI), the species was determined to be Yarrowia lipolytica (99.92% homology). Figure 1 This is a scanning electron micrograph of Yarrowia lipolytica PT3309. The strain of Yarrowia lipolytica PT3309 is deposited in Guangdong Provincial Microbiological Culture Collection Center (deposit number: GDMCC 65342, deposit address: No. 100, Xianlie Middle Road, Yuexiu District, Guangzhou City, Guangdong Province).

[0041] 18S rRNA nucleotide sequence (IS2625-1)

[0042]

[0043] Example 2 Characteristic Detection of Yarrowia lipolytica PT3309

[0044] 1. Growth Curve Determination

[0045] A 1% inoculum of PT3309 bacterial solution at a concentration of 1×108 CFU / mL was inoculated into MTB culture medium and cultured in a shaker at 32°C and 100 rpm. The absorbance of the fermentation broth at OD600 was measured every 2 hours using a microplate reader. The results showed ( Figure 2 ), the PT3309 strain entered the logarithmic growth phase after 10 h and the stationary phase after 30 h.

[0046] 2. Tolerance test

[0047] Table 1 Survival rates of Yarrowia lipolytica PT3309 and CICC1675 in artificial gastric and intestinal fluids (*, P<0.05)

[0048]

[0049] Overnight cultures of Yarrowia lipolytica PT3309 and Yarrowia lipolytica CICC1675 (reference strains) were washed three times with PBS buffer, centrifuged, and resuspended in PBS. The resuspended culture was divided into two aliquots: one aliquot was plated and counted as N0, and 500 μL of the other aliquot was added to 4.5 mL of artificial gastric and intestinal fluids. The cells were incubated at 32°C with a shaker at 100 rpm for 1 and 3 hours, respectively, and then plated and counted as N1. Survival rate (%) = N1 / N0 × 100%. Artificial gastric fluid was prepared by dissolving 0.2 g NaCl and 0.35 g pepsin in 100 mL of triple-distilled water, adjusting the pH to 3, and filter-sterilizing. Artificial intestinal fluid was prepared by dissolving 0.2 g NaCl and 0.1 g trypsin in 100 mL of triple-distilled water, adjusting the pH to 8 (Solution A). 1.2 g ox bile salt was dissolved in 100 mL of triple-distilled water, adjusting the pH to 8 (Solution B). Liquid A and Liquid B were mixed in a 1:2 ratio and sterilized by filtration. CICC1675 was purchased from the China Industrial Microbiological Culture Collection (https: / / www.china-cicc.org / cicc / detail2 / ?sid=1824) and used as a control. The results showed that PT3309 was highly tolerant to artificial gastric and intestinal fluids, suggesting that it can withstand the digestive environment of the gastrointestinal tract and function better. Compared to the standard strain CICC1675, PT3309 survived better in artificial gastric fluid, and both strains showed similar resistance to intestinal fluid (Table 1).

[0050] 3. Adhesion test on colonic epithelial cells

[0051] Human colon cancer cells, Caco2, were plated in 6-well plates in a complete culture medium consisting of 20% FBS, 1% Sodium Pyruvate, 1% MEM NEAA, 1% GlutaMAX, and 77% MEM. The culture medium was changed every two days until polarized. Overnight cultures of PT3309 and CICC1675 were washed twice with PBS and resuspended in MEM. The resuspended culture was divided into two aliquots, one of which was counted as N0. The other aliquot was added to Caco2 cells (500 μL per well) and incubated at 37°C for 2 hours. The cells were then removed and washed three times with PBS. 1 mL of trypsin was added to each well, and the cells were digested at 37°C for 3 minutes. After digestion, the cells were pipetted and mixed thoroughly, and the cells were plated and counted as N1. The adhesion rate (%) = N1 / N0 × 100%. The results showed that PT3309 had stronger adhesion to colonic epithelial cells than the standard strain, facilitating longer-term colonization in the intestine and prolonging the therapeutic effect.

[0052] Table 2. Adhesion rate of Yarrowia lipolytica PT3309 and CICC1675 to Caco2 cells (*, P < 0.05)

[0053]

[0054] Example 3 Alleviating Effects of Yarrowia lipolytica PT3309 on Inflammatory Bowel Disease in Wild-Type Mice

[0055] 6-8 week old male C57BL / 6J mice were adaptively fed for 1 week and then randomly divided into four groups (blank group, model group, model group + PT3309 colonization group, model group + PT3309 biomass group), with 6 mice in each group.

[0056] On days 1-14, the PT3309 bacterial solution was cultured for 2 days, resuspended in physiological saline at a dose of 5×109 CFU / kg, and administered to mice by gavage; the PT3309 biomass group prepared the bacterial solution at the same dose and then centrifuged it, washed twice with physiological saline, dried in an oven at 60°C to constant weight, dissolved with physiological saline, and administered to mice by gavage; the normal control group and the inflammatory bowel disease modeling group were gavaged with the same volume of sterile physiological saline. On days 15-23, the blank group drank water normally, and the other three groups of mice were given drinking water containing 3% dextran sodium sulfate (DSS) to establish a colitis model. After the modeling began, the weight, diarrhea, and bloody stools of the mice were recorded daily. The results are as follows: Figure 3 As shown, A is the weight change of mice; B is the diarrhea score of mice; C is the rectal bleeding or bloody stool of mice. Figure 3 Compared with the model group, the inflammatory bowel disease status of mice colonized with PT3309 was significantly improved. Similarly, mice gavaged with PT3309 biomass showed improvements in weight loss, diarrhea, and bloody stools compared with the model group.

[0057] On the 23rd day, mice in each group were gavaged with fluorescein isothiocyanate-dextran (FITC-dextran) fluorescent reagent (200 mg / kg). Blood was collected 4 hours later to detect the fluorescence intensity in the plasma and the intestinal permeability of the mice. The results are as follows: Figure 4 A and 4B. Compared with the model group, the FITC-dextran fluorescence intensity in the blood of PT3309-colonized mice was significantly weakened, indicating that PT3309 colonization improved the intestinal damage caused by DSS in mice. All groups of mice underwent colonoscopy, and the results were as follows: Figure 5 As shown in A, compared with the model group mice, the colon wall of PT3309-implanted mice was smoother, bleeding spots were reduced, and ulcer lesions were improved. The colon tissue was taken for HE staining, and the results were as follows Figure 5 As shown in Figure B, compared with the model group, the pathological damage of the colon tissue of the PT3309-implanted mice was significantly reduced, the edema of the submucosal layer was improved, and the infiltration of inflammatory cells was reduced. After the mice in each group were sacrificed, the colon and cecum were removed, placed on graph paper, and photographed. The colon length was calculated. One of the phenotypic characteristics of ulcerative colitis is intestinal shortening. Figure 6 As shown in A and 6B, the colon length of PT3309-colonized mice was significantly restored. After taking pictures, the colon tissue was immediately stored in a -80°C refrigerator. 30 mg of frozen colon tissue was taken, 300 μL of protein lysis buffer was added, and the mixture was ground and lysed on ice for 1 hour. The colon tissue protein was extracted and the protein concentration was determined using a BCA protein quantification kit. The expression of tight junction proteins Occludin and Claudin-1 was detected by western blot. The results showed that PT3309 colonization improved the DSS-induced decrease in tight junction protein expression in the mouse colon and restored the intestinal barrier. 20 mg of frozen colon tissue was taken, total RNA was extracted, and the expression of inflammatory factors such as IL-1β, IL-6, and TNF-α was detected using RT-PCR technology. Results ( Figure 7 ) showed that inflammatory cytokine levels in PT3309-colonized mice were significantly lower than in the modeling group. Similarly, oral administration of heat-killed PT3309 biomass significantly improved colitis-related symptoms in mice, demonstrating that PT3309 biomass can also effectively alleviate DSS-induced colitis in mice. However, in contrast, the effects of live bacteria colonization persisted in the intestine, and the PT3309-colonized group exhibited a more pronounced therapeutic effect.

[0058] Example 4: Alleviating Effect of Yarrowia lipolytica PT3309 on Inflammatory Bowel Disease in ABX Mice

[0059] 6-8 week old male C57BL / 6J mice were adaptively fed for 1 week and then randomly divided into two groups (model group and model group + PT3309 colonization), with 6 mice in each group.

[0060] On days 1–3, ampicillin (1 g / L), vancomycin (0.5 g / L), neomycin (1 g / L), metronidazole (1 g / L), fluconazole (0.5 g / L), and amphotericin B (0.1 g / L) were added to the drinking water of the two groups of mice to perform intestinal flora clearance, namely, ABX mice.

[0061] On days 4-18, PT3309 bacterial solution (5×109 CFU / kg) was administered to mice by oral gavage (model+PT3309 group); the model group was administered with the same volume of sterile saline by oral gavage.

[0062] On days 19-25, both groups of mice were given drinking water containing 3% DSS to establish a colitis model. During the modeling process, the weight, diarrhea score, and bloody stool of the mice were recorded. Figure 8 As shown, A is the weight change of mice; B is the bloody stool of mice; C is the diarrhea score of mice. Figure 8 It can be seen that compared with the mice in the model group, the symptoms of inflammatory bowel disease were significantly alleviated in mice colonized with Yarrowia lipolytica PT3309.

[0063] On the 25th day, mice in each group were given 200 mg / kg FITC-dextran fluorescent reagent. Blood was collected 4 hours later to detect the fluorescence intensity in the plasma, which reflects the intestinal permeability of mice. The results are as follows: Figure 9 Compared with the model group, PT3309 colonization significantly improved DSS-induced intestinal damage. All groups of mice underwent colonoscopy. Figure 10 As shown in A, compared with the model group mice, the colonic bleeding spots of mice colonized with Yarrowia lipolytica PT3309 were reduced and the ulcer lesions were improved. Colon tissue was cut and fixed in paraformaldehyde fixative for 24 hours, then embedded in paraffin and sectioned. Then, hematoxylin-eosin (HE) staining was performed and the inflammation of colon tissue was observed under a microscope. Figure 10 As shown in Figure B, compared with the model group, the colon villi of the mice in the PT3309 group were well-integrated and had no obvious inflammatory infiltration. Pathological sections showed that Yarrowia lipolytica PT3309 significantly alleviated the colon lesions in ABX inflammatory bowel disease mice. After the two groups of mice were sacrificed, the colon and cecum were removed, placed on graph paper, and photographed. The colon length was calculated. The results showed that the colon length of the mice colonized with Yarrowia lipolytica PT3309 was significantly longer than that of the mice in the model group ( Figure 11, A is a colon photo, B is a colon length statistical chart), indicating that Yarrowia lipolytica PT3309 has an improving effect on the colon length of ABX inflammatory bowel disease mice. Frozen colon tissue was taken to detect the expression of tight junction proteins Occludin and Claudin-1; the results showed that PT3309 colonization improved the DSS-induced decrease in tight junction protein expression in the colon of ABX mice and restored the intestinal barrier. Frozen colon tissue was also taken to detect the expression of inflammatory factors such as IL-1β, IL-6 and TNF-α. The results are as follows Figure 11 As shown in Figure C, the levels of inflammatory factors in ABX mice colonized with Yarrowia lipolytica PT3309 were significantly lower than those in the model group. These results indicate that the therapeutic effect of PT3309 on inflammatory bowel disease can be independent of the intestinal flora environment.

Claims

1. Yarrowia lipolytica strain PT3309, deposited in Guangdong Provincial Microbiological Culture Collection Center with the accession number GDMCC 65342.

2. Use of Yarrowia lipolytica PT3309 with a deposit number of GDMCC 65342 in the preparation of the following products: (1) Products for the prevention or treatment of inflammatory bowel disease (IBD); (2) Products that regulate the balance of intestinal flora; (3) Products with antioxidant activity; (4) Products that repair the intestinal barrier; in, The product is a medicine, food or probiotic preparation.

3. The use according to claim 2, characterized in that: The inflammatory bowel disease (IBD) is ulcerative colitis or Crohn's disease; The regulation of the intestinal flora balance includes increasing the abundance of beneficial bacteria or inhibiting the proliferation of harmful bacteria.

4. The use according to claim 2, characterized in that: The medicine is an oral preparation, suppository or injection; The food includes functional food, special medical food, and health care product; The probiotic preparation contains live bacteria, inactivated bacteria or strain metabolites.

5. The use according to claim 2, characterized in that: The therapeutic effects of the product include improving colon pathological damage, reducing the expression of colon inflammatory factors or restoring intestinal barrier function.

6. A probiotic preparation, characterized in that: The invention comprises live bacteria, freeze-dried bacterial powder, heat-inactivated bacterial biomass or strain metabolites of the Yarrowia lipolytica PT3309 according to claim 1.

7. The probiotic preparation according to claim 6, characterized in that: Tolerant to the digestive environment of the gastrointestinal tract; has stronger adhesion to colonic epithelial cells; viable bacterial count ≥ 1×106 CFU / g or 1.0×106 CFU / g.

8. A pharmaceutical composition, characterized in that: The invention comprises the live bacteria, freeze-dried bacterial powder, heat-inactivated bacterial biomass or strain metabolites of Yarrowia lipolytica PT3309 according to claim 1, and a pharmaceutically acceptable carrier.

9. A functional food, characterized in that: The food comprises live bacteria, freeze-dried bacterial powder, heat-inactivated bacterial biomass or strain metabolites of Yarrowia lipolytica PT3309 according to claim 1, wherein the food is prepared by a fermentation process or by directly adding bacteria, and is selected from fermented dairy products, fermented vegetable and fruit juices, biscuits, beverages or nutritional supplements.

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