Witzia coagulans for regulating mood health and relieving anxiety and application of Witzia coagulans

Abstract

The invention relates to Witzia ciliaris capable of regulating mood health and relieving anxiety and an application of the Witzia ciliaris. The Witzia ciliaris is separated from a healthy human excrement sample. According to the present invention, the Witzia ciliata KY009 can regulate the levels of 5-hydroxytryptamine, brain-derived neurotrophic factors and cortisol so as to provide the anti-depression effect, can significantly reduce the contents of hippocampal proinflammatory factors such as IL-1beta, IL-6 and IFN-alpha, and has the neuroinflammation inhibition activity. The strain and the composition thereof can be used for preparing medicines for treating depression, functional foods for relieving depressive mood and health-care products for improving mood, play a therapeutic role by correcting immune imbalance state of a body and regulating neuroinflammation, and provide a new microbial intervention strategy for treatment of depression and related mood disorders.

Description

Technical Field

[0001] The present invention relates to the field of microbial medicine, and particularly to Weissella coagulans for regulating emotional health and alleviating anxiety. Background Art

[0002] Depression, also known as Depressive Disorder, is a common mental disorder with persistent low mood, loss of interest and pleasure, and decreased energy as its core symptoms. It may also be accompanied by manifestations such as changes in appetite, sleep disorders, self-blame and self-condemnation, inattention, and even suicidal thoughts or behaviors. The onset of depression is multi-factorial, including genetic factors, as people with a family history of depression have a higher risk of developing the disease; neurotransmitter disorders, such as imbalances in serotonin, dopamine, etc.; abnormal brain structure and function, such as hippocampal atrophy, which may be related to depression; and psychosocial factors, such as long-term stress and major traumatic experiences, which may also induce depression. For patients themselves, it seriously affects the quality of life, leading to a decline in work and learning efficiency, social withdrawal, and may also affect physical functions, increasing the risk of developing other diseases. Severe depression patients may choose to commit suicide, causing huge losses to families and society. For families and society, family members need to spend a lot of time and energy taking care of patients, which may result in economic burdens and psychological pressures. At the social level, depression leads to a decline in productivity and increases the consumption of medical resources.

[0003] Depression is mainly a polygenic genetic disease with a heritability of 30%-50%. In recent years, other pathogenic factors have gradually been discovered. Domestic and foreign studies have shown that immunocompetent cells in the central nervous system, especially microglia, participate in the inflammatory response by releasing various pro-inflammatory factors in the brain, such as Tumor necrosis facter α and Interleukin 1β, etc., thus increasing the risk of depression. Some studies have shown that the levels of inflammatory factors in the peripheral blood of depression patients increase, the expression of inflammatory genes is up-regulated, the white blood cell count and ratio increase, and the ratio of CD4 + and CD8 + T cell ratio increases. In addition, the abnormal activation of inflammatory metabolic pathways such as kynurenine metabolism is also closely related to the pathophysiology of depression. Therefore, central and peripheral inflammatory responses may jointly regulate the course of depression, but central inflammation mainly affects brain function, while peripheral inflammation affects the whole body through blood circulation.

[0004] The connection between the gut microbiota and mental disorders has become a research hotspot. Studies have shown that the use of antibiotics may increase the risk of various mental disorders, including depression, anxiety, and schizophrenia, which is related to the impact of antibiotics on gut microbial diversity. More and more studies have indicated that compared with healthy people, the gut microbial composition of patients with depression has changed significantly. Although the research results vary, the enrichment of pro-inflammatory bacteria and the reduction of anti-inflammatory bacteria in the gut of patients with depression are commonly found, further supporting the inflammatory hypothesis of depression. Gut microbiota can also interact with the host through its metabolites such as short-chain fatty acids, neurotransmitters, and trimethylamine N-oxide, affecting mood and behavior. With the in-depth study of the potential pathological basis of the microbiota-gut-brain axis in depression, probiotic therapy has been found to be a potential treatment for depression. Probiotics refer to active microorganisms that help maintain the balance of gut microbiota and are beneficial to individual health. Common ones include Lactobacillus and Bifidobacterium. Probiotics can maintain gut immune homeostasis, promote normal individual development, and relieve negative emotions such as stress and anxiety. Specifically, probiotics can produce and transmit neuroactive substances such as serotonin (5-hydroxytryptamine, abbreviated as 5-HT) and gamma-aminobutyric acid. After these molecular signals act on the microbiota-gut-brain axis, they can reduce the depressive mood of patients and improve cognitive ability. More and more studies have shown that oral probiotics can be used as an adjuvant therapy for mental disorders such as depression. Summary of the Invention

[0005] Weizmannia coagulans KY009 was deposited on January 20, 2025 at the China General Microbiological Culture Collection Center, with the deposit address being No. 3, Yard 1, Beichen West Road, Chaoyang District, Beijing, and the deposit number being CGMCC NO. 33480.

[0006] Furthermore, the 16S rDNA of the Weizmannia coagulans is shown as SEQ ID NO: 3.

[0007] The Weizmannia coagulans was isolated from feces. Further, it was isolated from human feces.

[0008] The composition can be a food composition, a pharmaceutical composition, a health product composition, or a functional bacterial agent, etc.

[0009] A pharmaceutical composition, a composition comprising Weissella coagulans KY009 and a pharmaceutical excipient. The excipient in the pharmaceutical composition can be a diluent / filler selected from microcrystalline cellulose, starch (corn / potato), lactose, mannitol, calcium carbonate; a binder selected from hydroxypropyl methylcellulose (HPMC), gelatin, polyvinylpyrrolidone (PVP); a disintegrant such as sodium carboxymethyl starch (CCNa), low-substituted hydroxypropyl cellulose (L-HPC). The lubricant is selected from magnesium stearate, silica, talc. The coating material is selected from gastric-soluble / enteric-coated (such as acrylic resin, shellac); a protective agent for maintaining the stability of the bacterial agent, selected from trehalose, skim milk powder, glycerol, etc. The pharmaceutical composition can further be added with a targeted delivery component (such as a pH-sensitive polymer for colon release).

[0010] The food composition further includes prebiotics selected from fructooligosaccharides (FOS), galactooligosaccharides (GOS), inulin, resistant dextrin (promoting strain colonization), nutrients selected from vitamin B group, zinc (enhancing immune synergy), dietary fiber (such as polydextrose); flavoring / odor-correcting agents selected from citric acid, stevioside, natural fruit powder (improving palatability). The stabilizer is selected from pectin, xanthan gum (preventing bacterial sedimentation).

[0011] The functional bacterial agent mainly includes a live bacterial agent and optionally a culture medium composition, such as yeast extract, soy peptone, and can further include other probiotics co-cultured to enhance the effect, selected from Clostridium butyricum, Lactobacillus: such as Lactobacillus acidophilus, Lactobacillus rhamnosus; Bifidobacterium: such as Bifidobacterium infantis, Bifidobacterium longum; yeast: Saccharomyces boulardii, etc. Further, the functional bacterial agent can also include a carrier material such as diatomaceous earth, corn starch (for solid-state fermentation bacterial agent); and a synergist: short-chain fatty acid salts (such as sodium butyrate), plant extracts (such as curcumin, anti-inflammatory synergy).

[0012] The bacterial agent can be in various forms such as capsules, tablets, powders, drops, granules, microencapsulated particles, etc. Capsules and tablets are preferred as the pharmaceutical composition, powders are preferred as the food composition, and microencapsulated particles are preferred as the functional bacterial agent. More preferably, sodium alginate and the like are added for embedding to enhance acid and heat resistance during counting.

[0013] The administration route can be oral, gavage / tube feeding, topical administration, etc. Oral administration is the most preferred recommendation, and suppositories can also be used when needed for female microecological regulation.

[0014] The concentration of Weissella coagulans in the probiotic composition is 1×10 7 to 1×10 10 CFU / g, preferably 1×10 9 CFU / g.

[0015] Use of Weissella coagulans KY009 and a composition and a functional bacterial agent containing the same in the preparation of a medicament for relieving depressive mood, treating and / or preventing depression by correcting the immune imbalance state of the body, neuroregulation, and neuroinflammatory regulation; use in the preparation of a food composition capable of relieving depression; use in the preparation of a health product composition capable of relieving depression.

[0016] Among them, correcting the immune imbalance state of the body is achieved by regulating the levels of cytokines in the body.

[0017] Among them, the neuroinflammatory regulation effect refers to inhibiting the activity of neuroinflammation by significantly reducing the contents of pro-inflammatory factors IL-1β, IL-6, and IFN-α in the hippocampal region.

[0018] Beneficial effects The method of the present invention relieves problems such as depressive mood by supplementing probiotics. First, the probiotics of the present invention are obtained by isolating from normal human feces and are safer. Second, long-term use of the probiotics of the present invention also has an obvious effect of relieving depression. Finally, long-term use of traditional drugs will cause humans to develop dependence and drug resistance to the drugs, while the use of probiotics will not, so there is a large space for sustainable development. Description of the drawings

[0019] Figure 1 Gram staining (left) and colony morphology diagram (right) of Weissella coagulans KY009.

[0020] Figure 2 The forced swimming test (Forced swimming time, FST) of mice measures the struggling swimming time of mice in a fiberglass tank.

[0021] Figure 3 The open field test (Open field test, OFT) of mice measures the movement time, movement distance, and time spent in the targeted quadrant of mice, respectively.

[0022] Figure 4The elevated plus maze experiment in mice was used to detect the residence time of mice in the open area (Open arm resideNormale time), the movement distance in the open area (Openarm movementdistaNormale), and the number of entries into the central area (Number of central area entries).

[0023] Figure 5 The content of 5-HT in the serum of mice.

[0024] Figure 6 The content of corticosterone in the serum of mice.

[0025] Figure 7 The content of cortisol in the serum of mice.

[0026] Figure 8 The content of BDNF in the serum of mice.

[0027] Figure 9 The content of IL-1β in the hippocampus of mice.

[0028] Figure 10 The content of IL-6 in the hippocampus of mice.

[0029] Figure 11 The content of IFN-α in the hippocampus of mice. Specific implementation method

[0030] Isolation, screening and identification of Lactobacillus plantarum 1. Strain isolation and screening The fecal sample was evenly mixed with PBS, heated in a water bath at 80 °C for 10 min, and serially diluted 10 -2 ~10 -6 . 100 μL was taken and evenly spread on MRS medium, and anaerobically cultured at 37 °C for 24 - 48 h. When colonies formed, the morphological characteristics of the colonies were observed, and single colonies conforming to the morphological characteristics of Weissella coagulans were picked out.

[0031] 2. Molecular identification Universal primer sequences for 16S rDNA amplification: 27F: 5'-AGAGTTTGATCMTGGCTCAG-3' (SEQ ID NO: 1) 1492R: 5'-TACGGYTACCTTGTTACGACTT-3' (SEQ ID NO: 2) Table 1 PCR amplification reaction system

[0032] Prepare a 1% agarose gel (1g agarose plus 100mL TBE buffer) and boil it 2-3 times. When cooled to approximately 55°C, add 10μL of 4S Green buffer, mix thoroughly, and pour into a gel casting tank. Once solidified, add 1μL of loading buffer and 5μL of the PCR product mixture to the gel wells. Run gel electrophoresis at 220V for 30 minutes. If a band appears at the target band (1500bp), send the sample to the Shanghai branch of Beijing Liuhe BGI Genomics Co., Ltd. for 16S rDNA sequencing. Compare the sequencing results on the ezbiocloud website.

[0033] PCR product sequencing results: The sequencing results were compared on the ezbiocloud website, and strain KY009 was identified as Weizmannia coagulans.

[0034] Weizmannella coagulans: 3. Morphological identification: The KY009 bacteria were stained using the Gram staining method, and their morphology was observed under a 100× oil immersion microscope. The specific operation steps are as follows. Inoculate the KY009 bacteria into MRS solid medium and culture them in an anaerobic workstation at 37 °C for 48 h. Take a small amount of single colony of Weizmannia coagulans KY009, dip it into 2 μL of physiological saline, and smear it clockwise into a uniform thin circular shape of about 1 cm2. Place it in a normal temperature environment until the bacterial solution dries. Pass the glass slide through the flame of an alcohol lamp 1 - 2 times for fixation, taking care not to overheat, and it is appropriate when the glass slide is not hot to the touch. Drop the crystal violet staining solution onto the bacteria and stain for 1 min, then wash with water. Drop the iodine solution and stain for 1 min, then wash with water. Drop the decolorizing solution, shake the glass slide, decolorize for 30 s, wash with water, and blot off the moisture. Drop the safranin staining solution and stain for 1 min, then wash with water. Blot off the excess moisture with filter paper and perform microscopy under a 100× oil immersion microscope.

[0035] The results of the Gram staining microscope showed that it was a Gram-positive bacterium ( Figure 1 ), presenting a short rod-shaped morphology.

[0036] Weizmannia coagulans KY009 was deposited at the China General Microbiological Culture Collection Center on January 20, 2025. The deposit address is No. 3, Courtyard 1, Beichen West Road, Chaoyang District, Beijing. The deposit number is CGMCC NO. 33480, and the taxonomic name is Weizmannia coagulans.

[0037] 4. Behavioral tests: The behavioral tests were conducted from 9:00 am to 4:00 pm in the light cycle. All behavioral tests started on the 8th day, and the mice were allowed to acclimatize to the test environment for 2 hours before the test. Different batches of mice were used for different behavioral tests. After each animal experiment, the urine and feces were cleaned, and in order to eliminate the influence of the animal odor on the next experiment, the open field was washed with 75% ethanol solution.

[0038] In this invention, the CUMS (Chronic Unpredictable Mild Stress Model) was selected to construct a mouse depression model. The CUMS model is a widely used method for studying depression in animal experiments. By applying a series of unpredictable mild stressors, the CUMS model can induce behavioral and physiological changes similar to depression in mice. The specific manifestations of depressed mice include increased anxiety, unbalanced diet, and lack of enthusiasm for free movement, etc.

[0039] Before constructing the model, all mice were weighed and randomly divided into 3 groups, with 10 mice in each group. Weizmannia coagulans KY009 was suspended or dissolved in physiological saline, and the bacterial suspension solution for gavage was prepared freshly before use. The administration frequency was once a day.

[0040] In this experiment, male C57BL / 6J mice at 5 weeks of age with a body weight of 18 ± 2 g were used. The mice were acclimated for 7 days, and then the CUMS model was established for a total of 28 days. The stressors selected for constructing the CUMS mouse model included: (1) water deprivation for 24 h, (2) restraint in a restraint cylinder for 2 h, (3) tail suspension for 1 min, (4) cage shaking for 10 min, (5) cage tilting at 45˚ for 24 h, (6) food deprivation for 24 h, and (7) keeping the cage wet overnight (200 mL / cage). Randomness should be maintained when selecting stressors, and the interval between the same stressor should be greater than 7 days.

[0041] The average body weight of the mice in the blank control group (Normal) was 26.1 g on the 28th day, and the average body weight of the CUMS model mice (CUMS) was 22.5 g on the 28th day. The average body weight of the mice in the CUMS group was significantly lower than that of the mice in the Normal group, which was in line with the characteristics of the CUMS mouse model.

[0042] Blank control group (Normal): Normal mice were gavaged with 0.2 mL of 0.85% saline. CUMS model group (CUMS): Mice were induced with CUMS and gavaged with 0.2 mL of 0.85% saline; Intervention group of Weizmannia coagulans KY009 in the CUMS model (CUMS+KY-009): Mice were induced with CUMS and gavaged with Weizmannia coagulans KY009 at a dose of 10 9 CFU / mouse / day. To verify the technical effect of the Weizmannia coagulans screened in the present invention, the inventor also purchased Weizmannia coagulans products from other sources. (Purchased from Xi'an Taikang Bioengineering Co., Ltd.): Another strain of Weizmannia coagulans was isolated from the commercially available Weizmannia coagulans probiotic product as a control strain (control Weizmannia coagulans), and it was compared with the Weizmannia coagulans screened in the present invention. The mice were also gavaged with 10 9 CFU / mouse / day (CUMS+WC).

[0043] (1)Forced swimming test (FST): Mice were placed in a glass cylinder (25 cm high, 10 cm in diameter) filled with water (22°C) to a height of 18 cm. The test duration was 6 minutes, and the percentage of immobility time was recorded. "Immobility" was defined as only slightly moving the tail or front paws to keep the head floating on the water surface, with the front paws usually placed on both sides of the body. Swimming was defined as actively using the front paws to move forward, with the body usually parallel to the cylinder wall. Climbing was defined as actively using the front paws to grasp the cylinder wall, with the body perpendicular to the cylinder wall. Video recording was started before placing the animals in the water tank. The mice were grasped by the tail and slowly lowered into the water. Once the mouse was in the water, the tail was slowly released. This method was used to prevent the animal's head from being immersed in the water and affecting the results. When all the mice were in the water tank, the countdown on the stopwatch was started. The usual test length for mice was 6 min.

[0044] The results are as Figure 2 shown. In the forced swimming experiment, compared with the Normal group, the struggling swimming time of mice in the CUMS group was significantly lower than that in the Normal group; the swimming time of mice in the CUMS+KY009 group was significantly higher than that in the CUMS group, while the performance of mice in the CUMS+WC group (intragastric administration of control Weissella) was similar to that in the CUMS group, indicating that the Weissella KY009 isolated and screened by the inventor has the tendency to reduce mouse depression.

[0045] (2)Open field test (OFT): The open field was a 40 cm × 40 cm area, with a 20 cm × 20 cm center and 35 cm high walls around. During the test, the mice were placed in the center of the open field, and their behaviors were recorded for 10 minutes. A video tracking system (Smart) was used to record the movement distance and the time spent in the central and peripheral areas. Each mouse was placed separately in the center of the open box and allowed to freely explore for 2 minutes before the test. The behaviors of each mouse in the subsequent 4 min were recorded, including the number of grids crossed by the front limbs of the animal, the number of times of hind limb standing, and the time spent moving in the designated central area (20×20 cm) of the box.

[0046] The results are as Figure 3 shown. The time and distance that mice in the CUMS group moved in the entire open field and the time they stayed in the central area were significantly lower than those in the Normal group; the time and distance that mice in the CUMS+KY009 group moved in the open field and the time they stayed in the central area were significantly higher than those in the CUMS group, while the performance of mice in the CUMS+WC group (intragastric administration of control Weissella) was similar to that in the CUMS group. It shows that the intervention of KY009 can significantly improve the autonomous exploration ability and motor vitality of mice and improve emotions such as anxiety and depression.

[0047] (3)Elevated plus maze (EMP): The maze is made of black stainless steel and consists of four arms (30 cm long and 5 cm wide): two enclosed arms (black walls 30 cm high) and two open arms (0.5 cm high at the edges). The four arms are connected by a central platform (5 cm × 5 cm), and the maze is 50 cm high. Each mouse starts a 5-minute test from the central platform facing an open arm. The video tracking system records the time spent in the open arms and the number of entries into the open and enclosed arms (an entry into an arm is defined as all four paws entering the arm).

[0048] The results are as Figure 4 shown. The time and distance that the mice in the MS group moved in the open area of the EMP and the number of entries into the central area were significantly lower than those in the Normal group, indicating a significant increase in the anxiety-like behavior of the mice; the time and distance that the mice in the CUMS+KY009 group moved in the open area and the number of entries into the central area were significantly higher than those in the CUMS group, while the performance of the mice in the CUMS+WC group (intragastric administration of control Weissella) was similar to that in the CUMS group. It shows that KY009 intervention can significantly improve the autonomous exploration ability, locomotor activity and anxiety behavior of mice.

[0049] 5. Collect serum samples and tissue samples After the behavioral tests, blood was quickly drawn from the eye socket, and then the mice were sacrificed. The brain was placed in a petri dish on ice, and then the hippocampus was quickly removed. The hippocampus was placed in sterile physiological saline, homogenized thoroughly with a homogenizer, and then placed in a centrifuge. Set at 6000 r / min and 4 °C, centrifuge for 10 min, take the supernatant, aliquot the supernatant, retain the samples to be detected, and store the rest at -80 °C for future use; store the serum in a -80 °C refrigerator. When using the serum, it needs to be transferred from -80 °C to a 4 °C refrigerator 12 hours in advance and then used normally.

[0050] 6. After the behavioral tests, collect blood from the posterior orbital venous plexus of the mice and measure the serum biochemical indexes.

[0051] (1)5-HT Use an ELISA kit to detect the content of 5-HT in the serum. The results are as Figure 5 shown. Compared with the Normal group, the concentration of 5-HT in the serum of the mice in the CUMS group was significantly decreased, which indicates that stress has a negative effect on the brain regions of the mice in the MS group, making them show depressive characteristics; while the concentration of 5-HT in the serum of the mice in the CUMS+KY009 group was significantly increased, and the performance of the mice in the CUMS+WC group (intragastric administration of control Weissella) was similar to that in the CUMS group. This indicates that KY009 intervention can have a positive effect on the content of 5-HT in the body.

[0052] (2)Corticosterone Corticosterone is a corticosteroid 21-carbon steroid hormone produced by the adrenal cortex and is a glucocorticoid, also known as adrenosterone. It is produced by the stimulation of the adrenal cortex by ACTH (adrenocorticotropic hormone). In some specific non-human species, it is a precursor in the synthesis of another adrenal cortical steroid, aldosterone. Since stress increases the production of corticosteroids, corticosterone is a major stress indicator. The content of corticosterone in serum was detected using an ELISA kit, and the results are as Figure 6 shown. Compared with the Normal group, the concentration of corticosterone in the serum of mice in the CUMS group was significantly increased, while the concentration of corticosterone in the serum of mice in the CUMS+KY009 group was significantly decreased. The performance of mice in the CUMS+WC group gavaged with the control Weissella was similar to that in the CUMS group, and there was no obvious improvement.

[0053] (3)Cortisol Cortisol, also known as hydrocortisone, is a glucocorticoid hormone that has the strongest effect on carbohydrate metabolism and is extracted from the adrenal cortex. Cortisol is sometimes used specifically to refer to the basic "stress hormone". In daily life, when a subject is affected by emotions such as fear, anxiety, and high stress, cortisol will increase rapidly and be used as energy by decomposing amino acids, glucose, and fatty acids and transporting them into the blood. It is also known as the "stress or fight" hormone. The content of cortisol in serum was detected using an ELISA kit, and the results are as Figure 7 shown. Compared with the Normal group, the concentration of cortisol in the serum of mice in the CUMS group was significantly increased, while the concentration of cortisol in the serum of mice in the CUMS+KY009 group was significantly decreased. The performance of mice in the CUMS+WC group gavaged with the control Weissella was similar to that in the CUMS group, and there was no obvious improvement.

[0054] (4)BDNF BDNF, that is, brain-derived neurotrophic factor, is a major member of the neurotrophic family. A decrease in BDNF levels easily leads to a low mood in the host and triggers depression. The content of BDNF in serum was detected using an ELISA kit, and the results are as Figure 8 shown. Compared with the Normal group, the concentration of BDNF in the serum of mice in the CUMS group was significantly decreased, while the concentration of BDNF in the serum of mice in the CUMS+KY009 group was significantly increased. The performance of mice in the CUMS+WC group gavaged with the control Weissella was similar to that in the CUMS group, and there was no obvious improvement.

[0055] 7. Determination of the Contents of IL-1β, IL-6 and TFN-α in the Hippocampus (1)IL-1β The content of IL-1β in the hippocampus of mice was determined using a kit, and the results are as Figure 9 shown. Compared with the Normal group, the concentration of the inflammatory factor IL-1β in the hippocampus of mice in the CUMS group increased significantly, while the concentration of the inflammatory factor IL-1β in the hippocampus of mice in the CUMS+KY009 group decreased significantly. The performance of mice in the CUMS+WC group (intragastric administration of control Weizmannia) was similar to that in the CUMS group, and the concentration of IL-1β was relatively high.

[0056] (2)IL-6 The content of IL-6 in the hippocampus of mice was determined using a kit, and the results are as Figure 10 shown. Compared with the Normal group, the concentration of the inflammatory factor IL-6 in the hippocampus of mice in the MS group increased significantly, while the concentration of the inflammatory factor IL-6 in the hippocampus of mice in the KY009 group decreased significantly. The performance of mice in the CUMS+WC group (intragastric administration of control Weizmannia) was similar to that in the CUMS group, and the concentration of IL-6 was relatively high.

[0057] (3)IFN-α The content of IFN-α in the hippocampus of mice was determined using a kit, and the results are as Figure 11 shown. Compared with the Normal group, the concentration of the inflammatory factor IFN-α in the hippocampus of mice in the CUMS group increased significantly, while the concentration of the inflammatory factor IFN-α in the hippocampus of mice in the CUMS+KY009 group decreased significantly. The performance of mice in the CUMS+WC group (intragastric administration of control Weizmannia) was similar to that in the CUMS group, and IFN-α was relatively high.

[0058] The contents of inflammatory factors in the hippocampus of mice in each group are as Figures 9 - 11 shown. The contents of the pro-inflammatory cytokines IL-6, IFN-α and IL-1β in the serum of mice in the CUMS group were significantly higher than those in the Normal group, indicating that the immune system of the CUMS model mice was in a state of imbalance; after intervention with the probiotic KY009, the contents of the pro-inflammatory cytokines IL-6, IFN-α and IL-1β in the model mice decreased significantly, indicating that the probiotic KY009 can correct the immune imbalance state of the body by regulating the levels of cytokines in the body.

Claims

1. A Weizmannella coagulans strain, deposited in the General Microbiology Center of the China Culture Collection Administration of Microorganisms, with the deposit number being CGMCC No. 33480.

2. The Weizmannella coagulans according to claim 1, wherein the Weizmannella coagulans is isolated from healthy human feces; the Weizmannella coagulans is a Gram-positive bacterium in the form of a short rod; the 16S rDNA sequence of the Weizmannella coagulans is shown in SEQ ID NO:

3.

3. A pharmaceutical composition comprising the Weizmannella coagulans according to claim 1-2 and a pharmaceutically acceptable excipient, wherein the excipient is selected from one or more of a diluent, a binder, a disintegrant, a lubricant, a coating material or a protective agent.

4. The pharmaceutical composition according to claim 3, wherein the dosage form is selected from capsules, tablets, powders, drops, granules, or microencapsulated granules.

5. A food composition comprising Weizmannella coagulans and food-grade excipients, wherein the excipients include one or more of prebiotics, nutrients, flavorings, or stabilizers.

6. A functional bacterial agent comprising Weizmannella coagulans and a culture medium composition, other probiotics or synergists, wherein the other probiotics are selected from one or more of Clostridium butyricum, Lactobacillus, Bifidobacterium or Saccharomyces boulardii.

7. The pharmaceutical composition according to any one of claims 3-4, or the food composition according to claim 5, or the functional bacterial agent according to claim 6, wherein the concentration of Weissella coagulans in the composition is 1×10 7 to 1×10 10 CFU / g.

8. Use of the Weizmannella coagulans according to any one of claims 1 to 2 or the pharmaceutical composition according to any one of claims 3 to 4 in the preparation of a medicament for alleviating depression, treating and / or preventing depression by correcting the body's immune imbalance, neuromodulation, and neuroinflammation regulation.

9. The use according to claim 8, wherein the correction of the body's immune imbalance is achieved by regulating the level of cytokines in the body; wherein the neuroinflammation regulating effect is achieved by significantly reducing the levels of pro-inflammatory factors IL-1β, IL-6 and IFN-α in the hippocampus, thereby inhibiting the activity of neuroinflammation.

10. Use of the food composition according to claim 5 or the functional bacterial agent according to claim 6 in preparing a food composition capable of relieving depression, or in preparing a health product composition capable of relieving depression.

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